LYMPHOMA COMMITTEE - SWOG Stat 2017/RoS Spring 2017... · APRIL 26 - 29, 2017 SWOG LYMPHOMA 7...
Transcript of LYMPHOMA COMMITTEE - SWOG Stat 2017/RoS Spring 2017... · APRIL 26 - 29, 2017 SWOG LYMPHOMA 7...
APRIL 26 - 29, 2017 SWOG LYMPHOMA 1
LYMPHOMA COMMITTEE
APRIL 26 - 29, 2017 SWOG LYMPHOMA 2
CONTENTS
S1001 Phase II ............................................................................................................................................................... 6
S1204 Surveillance ...................................................................................................................................................... 17
S1608 Phase II ............................................................................................................................................................. 18
EAY131 Master Protocol / Phase II ............................................................................................................................ 20
APRIL 26 - 29, 2017 SWOG LYMPHOMA 3
Patient Registrations to Studies
By 12 Month Intervals
LYMPHOMA COMMITTEE
Screening registrations and registrations to Biologic only studies are excluded
SWOG LAPS MEMBER NCORP NON-SWOG
178
304
121
7996
42
0
50
100
150
200
250
300
350
Time of Registration
Jan 2011Dec 2011
Jan 2012Dec 2012
Jan 2013Dec 2013
Jan 2014Dec 2014
Jan 2015Dec 2015
Jan 2016Dec 2016
58
29
76
27
84
53
140
39
38
37
29
24
26
3819
25
APRIL 26 - 29, 2017 SWOG LYMPHOMA 4
Patient Registrations by Study and Arm LYMPHOMA COMMITTEE
Jul 2016
Dec 2016
Jan 2016
Jun 2016
Jul 2015
Dec 2015
All
Patients
S1001 DLBCL, I-II, PET-Adapted Therapy
Initial registration
R-CHOP x 3 0 14 20 158
R-CHOP x 6 0 0 0 1
0 14 20 159
PET-Directed Therapy
Continued R-CHOP 2 19 17 136
IFRT + Zevalin 1 1 0 13
3 20 17 149
9177 NHL, Dose-adj. EPOCH+/-Rituximab*
Total Registrations 0 0 1 19
C51101 CNS, Myelo/Non-myelo Chemo, PhII*
Total Registrations 3 0 0 8
E1411 MCL, RB+R, RBV+R, RB+LR, RBV+LR*
Total Registrations 4 9 18 86
E1412 DLBCL, R2CHOP vs RCHOP*
Total Registrations 3 9 0 38
* For non-SWOG coordinated studies only SWOG registrations are shown.
APRIL 26 - 29, 2017 SWOG LYMPHOMA 5
Non-SWOG Studies with SWOG-Credited Registrations
LYMPHOMA COMMITTEE
Studies with Accrual from July 2015 – December 2016
SWOG
Champion
Date
Activated
Date
Closed
Total
Accrual
9177 NHL, Dose-adj. EPOCH+/-Rituximab
M Fanale 04/13/12 160
No Progress Report Available
A051301 ABC DLBCL, Auto HCT and Ibrutinib/Placebo
P Stiff 07/15/16 0
No Progress Report Available
C51101 CNS, Myelo/Non-myelo Chemo, PhII
N Mohile 06/22/12 97
Most Recent Progress Report
E1411 MCL, RB+R, RBV+R, RB+LR, RBV+LR
B Till 06/08/12 09/09/16 373
Most Recent Progress Report
E1412 DLBCL, R2CHOP vs RCHOP
J Amengual 01/22/14 01/17/17 343
Most Recent Progress Report
APRIL 26 - 29, 2017 SWOG LYMPHOMA 6
S1001/II
S1001 Phase II
Coordinating Group: SWOG
A Phase II Trial of PET-Directed Therapy for Limited Stage Diffuse Large
B-Cell Lymphoma (DLBCL)
Participants:
SWOG, CTSU (Supported by Alliance, ECOG-ACRIN)
Study Chairs:
D Persky, S Park (Alliance), L Swinnen (ECOG-ACRIN)
Statisticians:
M LeBlanc, H Li
Data Coordinator:
J Jardine
Date Activated:
07/15/2011
Date Closed:
06/01/2016
SCHEMA
Objectives To assess the five-year progression-free survival
(PFS) rate in patients with newly diagnosed limited
stage diffuse large B-cell lymphoma using PET scan
to direct therapy after three cycles of R-CHOP.
To evaluate progression-free survival within the
PET+ and PET- subgroups of patients with newly
diagnosed limited stage diffuse large B-cell
lymphoma (DLBCL).
To evaluate the toxicity of this treatment regimen in
this patient population.
To evaluate the response probability in this patient
population.
To evaluate overall survival (OS) in the overall
population, and within the PET+ and PET- subgroups.
R
E
G
I
S
T
E
R
PET-
R-CHOPx 3*
*All patients who are early stage by CT but advanced stage by PET/CT at baseline
will receive R-CHOPx6
PET+
R-CHOPx1
IFRT + Zevalin
APRIL 26 - 29, 2017 SWOG LYMPHOMA 7
S1001/II
To estimate the rate of upstaging at baseline by PET
among patients newly diagnosed with limited stage
diffuse large B-cell lymphoma by CT imaging and
describe outcomes in patients upstaged by PET at
baseline to advanced DLBCL.
To evaluate the association of germinal center B-cell
subtype (GCB) vs stromal-1 vs stromal-2 gene
expression signatures with PFS and OS.
Patient Population Patients must have non-bulky Stage I or II de-novo
diffuse large B-cell non-Hodgkin's lymphoma
(DLBCL) which is positive for CD20. Patients who
have Stage I or II non-bulky disease based on
diagnostic CT scan, but are upstaged to Stage III or
IV based on FDG-PET evaluation, are also eligible.
Patients with primary mediastinal lymphoma,
testicular lymphoma, prior or simultaneous diagnosis
of indolent lymphoma, or post-transplant
lymphoproliferative disorder with DLBCL
morphology are not eligible. Patients may have either
measurable or evaluable limited-stage DLBCL.
Patients rendered free of measurable or evaluable
disease by virtue of biopsy (resection) are also
eligible. Patients with CNS involvement are not
eligible.
Patients must not have received prior chemotherapy,
radiation therapy, or antibody therapy for lymphoma.
Patients must be at least 18 years of age and have a
Zubrod performance status of 0-2. Patients must have
adequate renal, hepatic, cardiac and hematologic
function. Patients known to be HIV-positive are not
eligible.
Stratification/Descriptive Factors For registration step 1, patients will be described by
advanced stage based on local review of the baseline
PET/CT: yes vs no.
For registration step 2, patients will be described by
the positive PET/CT after three cycles of R-CHOP
based on centralized review: yes vs no.
Accrual Goals Assuming an ineligibility rate of 10%, we anticipate
needing to accrue 155 patients in order to obtain 140
eligible patients. Assuming that 15% of eligible
patients will have been upstaged at baseline by PET,
we expect that 120 patients will receive PET-directed
therapy. We further expect that 30 of these patients
will be PET-positive, assuming a PET-positive rate
of 25%. If the actual rate of PET-positivity is less
than 25%, accrual will continue until 30 eligible
patients in the FDG-PET-positive subgroup are
enrolled.
Summary Statement This study was closed to accrual on June 1, 2016,
after a total accrual of 159 patients, including one
patient who was upstaged to advanced stage DLBCL
based on local review of the baseline PET/CT. Two
patients are ineligible for initial registration, one due
to incorrect histology and one due to no required
baseline specimens submitted for pathology review.
One hundred fifty-four patients have been assessed
for toxicities on initial R-CHOPx3 therapy. One
patient died of sepsis five days after the last date of
treatment during the first cycle of treatment. Upon
review, this was found to be probably related to
protocol treatment. This patient also experienced
Grade 4 hematologic toxicities and febrile
neutropenia. An additional 27 patients experienced
Grade 4 hematologic toxicities, three of whom also
experienced Grade 4 non-hematologic toxicities
including febrile neutropenia (2), hyponatremia, and
sepsis.
The patient on R-CHOPx6 therapy did not experience
Grade 3 or greater toxicities.
One hundred forty-nine patients have been registered
to PET-directed therapy based on the availability of
the interim PET result, 137 of whom were interim
PET-negative and registered to the continued R-
CHOP therapy, and 12 of whom were interim PET-
positive and registered to the IFRT + Zevalin therapy.
One PET-negative patient is ineligible due to being
ineligible at Step 1. Major protocol deviations are
coded for two PET-negative patients who did not
received any PET-directed R-CHOP therapy; these
two patients are not evaluable for toxicities related to
PET-directed therapy.
Among 134 patients on the continued R-CHOP arm
that have been assessed for toxicities, one patient
died from hypoxia, which was possibly attributable to
treatment, and had also experienced Grade 4
neutropenia and respiratory, thoracic and mediastinal
disorders. Twelve additional patients on this arm
experienced treatment-related Grade 4 hematologic
toxicities, one of whom also experienced Grade 4
secondary leukemia. Two of the 12 patients assessed
for toxicities on the IFRT + Zevalin arm experienced
Grade 4 hematologic toxicities.
APRIL 26 - 29, 2017 SWOG LYMPHOMA 8
S1001/II
Registration by Institution
Initial Registration
Institutions
Total
Reg Institutions
Total
Reg
Alliance 40 Kentucky, U of 3
Rochester, Univ of 28 Fred Hutchinson CRC 2
ECOG-ACRIN 20 Greenville NCORP 2
Michigan CRC NCORP 8 Northwest NCORP 2
Arizona MC, U of 7 NRG 2
Upstate Carolina 7 St Luke's Mt State/PCRC NCORP 2
Kansas City NCORP 6 Virginia Mason MC/Northwest NCORP 2
Wichita NCORP 6 Essentia Hlth NCORP 1
Yale University 6 Montana NCORP 1
Loyola University 5 Southeast COR NCORP 1
City of Hope Med Ctr 4 Total (22 Institutions) 159
Hawaii MU-NCORP 4
Registration, Eligibility, and Evaluability
Initial Registration
Data as of February 23, 2017
TOTAL R-CHOP x 3 R-CHOP x 6
NUMBER REGISTERED 159 158 1
INELIGIBLE 2 2 0
Insufficient Documentation 1 1 0
Irreversible 1 1 0
ELIGIBLE 157 156 1
Analyzable, Pend. Elig. 153 152 1
RESPONSE ASSESSMENT
Determinable 149 148 1
Not Determinable 2 2 0
Too Early 6 6 0
ADVERSE EVENT ASSESSMENT
Evaluable 155 154 1
Too Early 2 2 0
APRIL 26 - 29, 2017 SWOG LYMPHOMA 9
S1001/II
Patient Characteristics
Initial Registration
Data as of February 23, 2017
R-CHOP x 3
(n=156)
R-CHOP x 6
(n=1)
AGE
Median 61.6 74.3
Minimum 18.5 74.3
Maximum 85.7 74.3
SEX
Males 80 51% 0 0%
Females 76 49% 1 100%
HISPANIC
Yes 7 4% 0 0%
No 142 91% 1 100%
Unknown 7 4% 0 0%
RACE
White 136 87% 1 100%
Black 6 4% 0 0%
Asian 10 6% 0 0%
Native American 1 1% 0 0%
Unknown 3 2% 0 0%
PET UPSTAGED
Yes 0 0% 1 100%
No 156 100% 0 0%
Treatment Summary
Initial Registration
Data as of February 23, 2017
TOTAL R-CHOP x 3 R-CHOP x 6
NUMBER ON PROTOCOL TREATMENT 4 4 0
NUMBER OFF PROTOCOL TREATMENT
REASON OFF TREATMENT
153 152 1
Treatment completed as planned 148 147 1
Adverse Event or side effects 2 2 0
Refusal unrelated to adverse event 0 0 0
Other - not protocol specified 1 1 0
Reason under review 1 1 0
MAJOR PROTOCOL DEVIATIONS 0 0 0
APRIL 26 - 29, 2017 SWOG LYMPHOMA 10
S1001/II
Number of Patients with a Given Type and Grade of Adverse Event
Initial Registration
Adverse Events Unlikely or Not Related to Treatment Excluded
Data as of February 23, 2017
R-CHOP x 3
(n=154)
Grade
R-CHOP x 6
(n=1)
Grade
ADVERSE EVENTS 0 1 2 3 4 5 0 1 2 3 4 5
ALT increased 130 21 3 0 0 0 1 0 0 0 0 0
AST increased 138 15 1 0 0 0 1 0 0 0 0 0
Abdominal pain 149 4 1 0 0 0 1 0 0 0 0 0
Agitation 152 1 1 0 0 0 1 0 0 0 0 0
Alkaline phosphatase increased 148 5 1 0 0 0 1 0 0 0 0 0
Allergic reaction 148 1 5 0 0 0 1 0 0 0 0 0
Alopecia 91 20 43 0 0 0 0 0 1 0 0 0
Anal hemorrhage 153 1 0 0 0 0 1 0 0 0 0 0
Anemia 74 59 13 8 0 0 0 1 0 0 0 0
Anorexia 134 14 5 1 0 0 0 1 0 0 0 0
Anxiety 148 2 4 0 0 0 1 0 0 0 0 0
Arthralgia 146 6 2 0 0 0 1 0 0 0 0 0
Back pain 150 3 1 0 0 0 1 0 0 0 0 0
Bloating 151 1 2 0 0 0 1 0 0 0 0 0
Blood bilirubin increased 152 2 0 0 0 0 1 0 0 0 0 0
Blurred vision 151 3 0 0 0 0 1 0 0 0 0 0
Bone pain 141 7 5 1 0 0 1 0 0 0 0 0
CD4 lymphocytes decreased 151 0 1 2 0 0 1 0 0 0 0 0
Catheter related infection 153 0 0 1 0 0 1 0 0 0 0 0
Chills 146 7 1 0 0 0 1 0 0 0 0 0
Concentration impairment 153 1 0 0 0 0 1 0 0 0 0 0
Confusion 153 1 0 0 0 0 1 0 0 0 0 0
Constipation 98 43 12 1 0 0 0 0 1 0 0 0
Cough 146 6 1 1 0 0 1 0 0 0 0 0
Creatinine increased 150 4 0 0 0 0 1 0 0 0 0 0
Dehydration 145 1 8 0 0 0 1 0 0 0 0 0
Depression 153 0 1 0 0 0 1 0 0 0 0 0
Diarrhea 135 15 1 3 0 0 1 0 0 0 0 0
Dizziness 142 12 0 0 0 0 1 0 0 0 0 0
Dry mouth 145 9 0 0 0 0 1 0 0 0 0 0
Dry skin 151 3 0 0 0 0 0 1 0 0 0 0
Dysgeusia 137 12 5 0 0 0 1 0 0 0 0 0
Dyspepsia 138 8 8 0 0 0 1 0 0 0 0 0
Dyspnea 141 8 2 3 0 0 0 1 0 0 0 0
Edema face 153 1 0 0 0 0 1 0 0 0 0 0
Edema limbs 145 7 1 1 0 0 0 1 0 0 0 0
Endocrine disorders-Other 153 0 0 1 0 0 1 0 0 0 0 0
Epistaxis 153 1 0 0 0 0 1 0 0 0 0 0
Eye disorders - Other, specify 152 2 0 0 0 0 1 0 0 0 0 0
Eye pain 153 1 0 0 0 0 1 0 0 0 0 0
Facial pain 152 2 0 0 0 0 1 0 0 0 0 0
Fall 153 0 1 0 0 0 1 0 0 0 0 0
Fatigue 48 81 21 4 0 0 0 1 0 0 0 0
Febrile neutropenia 140 0 0 11 3 0 1 0 0 0 0 0
APRIL 26 - 29, 2017 SWOG LYMPHOMA 11
S1001/II
R-CHOP x 3
(n=154)
Grade
R-CHOP x 6
(n=1)
Grade
ADVERSE EVENTS 0 1 2 3 4 5 0 1 2 3 4 5
Fever 141 11 2 0 0 0 1 0 0 0 0 0
Flank pain 153 1 0 0 0 0 1 0 0 0 0 0
Flatulence 152 2 0 0 0 0 1 0 0 0 0 0
Flu like symptoms 153 0 1 0 0 0 1 0 0 0 0 0
GERD 147 4 3 0 0 0 1 0 0 0 0 0
GI disorders-Other, specify 152 2 0 0 0 0 1 0 0 0 0 0
Gastritis 153 0 1 0 0 0 1 0 0 0 0 0
Gen disorders/admin site cond 152 2 0 0 0 0 1 0 0 0 0 0
Generalized muscle weakness 145 6 2 1 0 0 1 0 0 0 0 0
Glucose intolerance 153 0 1 0 0 0 1 0 0 0 0 0
Headache 142 12 0 0 0 0 1 0 0 0 0 0
Hematuria 153 1 0 0 0 0 1 0 0 0 0 0
Hemoglobin increased 153 1 0 0 0 0 1 0 0 0 0 0
Hemorrhoids 153 1 0 0 0 0 1 0 0 0 0 0
Hiccups 153 1 0 0 0 0 1 0 0 0 0 0
Hoarseness 152 1 1 0 0 0 0 1 0 0 0 0
Hot flashes 152 2 0 0 0 0 1 0 0 0 0 0
Hyperglycemia 135 10 5 4 0 0 1 0 0 0 0 0
Hyperhidrosis 151 2 1 0 0 0 1 0 0 0 0 0
Hyperkalemia 153 0 1 0 0 0 1 0 0 0 0 0
Hypernatremia 153 1 0 0 0 0 1 0 0 0 0 0
Hypertension 147 2 2 3 0 0 1 0 0 0 0 0
Hypoalbuminemia 138 8 8 0 0 0 0 1 0 0 0 0
Hypocalcemia 143 8 3 0 0 0 1 0 0 0 0 0
Hypokalemia 143 7 2 2 0 0 1 0 0 0 0 0
Hypomagnesemia 148 6 0 0 0 0 1 0 0 0 0 0
Hyponatremia 146 7 0 0 1 0 1 0 0 0 0 0
Hypophosphatemia 153 0 1 0 0 0 1 0 0 0 0 0
Hypotension 149 3 2 0 0 0 1 0 0 0 0 0
Infusion related reaction 136 2 16 0 0 0 1 0 0 0 0 0
Injection site reaction 153 0 1 0 0 0 1 0 0 0 0 0
Insomnia 134 12 8 0 0 0 1 0 0 0 0 0
Irregular menstruation 153 1 0 0 0 0 1 0 0 0 0 0
Lip infection 153 1 0 0 0 0 1 0 0 0 0 0
Localized edema 152 2 0 0 0 0 1 0 0 0 0 0
Lower GI hemorrhage 153 1 0 0 0 0 1 0 0 0 0 0
Lung infection 152 0 0 2 0 0 1 0 0 0 0 0
Lymphocyte count decreased 89 24 21 15 5 0 0 0 1 0 0 0
Memory impairment 152 2 0 0 0 0 1 0 0 0 0 0
Menorrhagia 153 1 0 0 0 0 1 0 0 0 0 0
Mucosal infection 153 0 1 0 0 0 1 0 0 0 0 0
Mucositis oral 129 18 6 1 0 0 0 1 0 0 0 0
Myalgia 147 7 0 0 0 0 1 0 0 0 0 0
Nail discoloration 151 3 0 0 0 0 1 0 0 0 0 0
Nasal congestion 153 1 0 0 0 0 1 0 0 0 0 0
Nausea 82 51 20 1 0 0 0 1 0 0 0 0
Neck pain 151 2 1 0 0 0 1 0 0 0 0 0
Neutrophil count decreased 99 5 10 13 27 0 1 0 0 0 0 0
Oral pain 151 0 2 1 0 0 1 0 0 0 0 0
Pain 149 1 4 0 0 0 1 0 0 0 0 0
Pain of skin 153 1 0 0 0 0 1 0 0 0 0 0
APRIL 26 - 29, 2017 SWOG LYMPHOMA 12
S1001/II
R-CHOP x 3
(n=154)
Grade
R-CHOP x 6
(n=1)
Grade
ADVERSE EVENTS 0 1 2 3 4 5 0 1 2 3 4 5
Papulopustular rash 153 1 0 0 0 0 1 0 0 0 0 0
Paresthesia 150 4 0 0 0 0 1 0 0 0 0 0
Peripheral motor neuropathy 149 4 1 0 0 0 1 0 0 0 0 0
Peripheral nerve infection 153 0 1 0 0 0 1 0 0 0 0 0
Peripheral sensory neuropathy 118 31 4 1 0 0 1 0 0 0 0 0
Phlebitis 153 0 1 0 0 0 1 0 0 0 0 0
Platelet count decreased 129 17 3 3 2 0 0 1 0 0 0 0
Postnasal drip 153 0 1 0 0 0 1 0 0 0 0 0
Presyncope 153 0 1 0 0 0 1 0 0 0 0 0
Productive cough 152 2 0 0 0 0 1 0 0 0 0 0
Proteinuria 153 1 0 0 0 0 1 0 0 0 0 0
Pruritus 150 3 1 0 0 0 1 0 0 0 0 0
Rash acneiform 152 2 0 0 0 0 1 0 0 0 0 0
Rash maculo-papular 146 7 1 0 0 0 0 1 0 0 0 0
Renal/urinary disorders-Other 152 2 0 0 0 0 1 0 0 0 0 0
Repro system/breast ds-Oth 152 1 1 0 0 0 1 0 0 0 0 0
Resp/thoracic/mediastinal ds 153 1 0 0 0 0 1 0 0 0 0 0
Scalp pain 153 1 0 0 0 0 1 0 0 0 0 0
Sepsis 152 0 0 0 1 1 1 0 0 0 0 0
Sinus bradycardia 152 2 0 0 0 0 1 0 0 0 0 0
Sinus tachycardia 152 2 0 0 0 0 1 0 0 0 0 0
Sinusitis 153 0 1 0 0 0 1 0 0 0 0 0
Skin infection 151 2 0 1 0 0 1 0 0 0 0 0
Skin/subq tissue ds-Other 149 5 0 0 0 0 1 0 0 0 0 0
Sore throat 148 5 1 0 0 0 1 0 0 0 0 0
Stomach pain 152 1 1 0 0 0 1 0 0 0 0 0
Stroke 153 0 0 1 0 0 1 0 0 0 0 0
Superficial thrombophlebitis 153 0 1 0 0 0 1 0 0 0 0 0
Thromboembolic event 153 0 1 0 0 0 1 0 0 0 0 0
Upper respiratory infection 147 0 7 0 0 0 1 0 0 0 0 0
Urinary frequency 144 9 1 0 0 0 1 0 0 0 0 0
Urinary incontinence 152 2 0 0 0 0 1 0 0 0 0 0
Urinary retention 153 1 0 0 0 0 1 0 0 0 0 0
Urinary tract infection 145 0 6 3 0 0 1 0 0 0 0 0
Urinary urgency 153 1 0 0 0 0 1 0 0 0 0 0
Urine discoloration 153 1 0 0 0 0 1 0 0 0 0 0
Vaginal infection 152 0 2 0 0 0 1 0 0 0 0 0
Voice alteration 152 1 1 0 0 0 1 0 0 0 0 0
Vomiting 141 8 5 0 0 0 0 1 0 0 0 0
Watering eyes 153 1 0 0 0 0 1 0 0 0 0 0
Weight gain 152 2 0 0 0 0 0 1 0 0 0 0
Weight loss 146 7 1 0 0 0 1 0 0 0 0 0
Wheezing 153 1 0 0 0 0 1 0 0 0 0 0
White blood cell decreased 97 15 11 17 14 0 0 0 1 0 0 0
Wound infection 153 0 1 0 0 0 1 0 0 0 0 0
MAX. GRADE ANY ADVERSE EVENT 2 21 65 38 27 1 0 0 1 0 0 0
APRIL 26 - 29, 2017 SWOG LYMPHOMA 13
S1001/II
Registration, Eligibility, and Evaluability
PET-Directed Therapy
Data as of February 23, 2017
TOTAL
Continued R
-CHOP IFRT + Zevalin
NUMBER REGISTERED 149 137 12
INELIGIBLE 1 1 0
Insufficient Documentation 1 1 0
Irreversible 1 1 0
ELIGIBLE 148 136 12
Analyzable, Pend. Elig. 143 131 12
RESPONSE ASSESSMENT
Determinable 130 124 6
Not Determinable 1 1 0
Too Early 17 11 6
ADVERSE EVENT ASSESSMENT
Evaluable 146 134 12
Not Evaluable 2 2 0
Treatment Summary
PET-Directed Therapy
Data as of February 23, 2017
TOTAL
Continued R
-CHOP IFRT + Zevalin
NUMBER ON PROTOCOL TREATMENT 3 3 0
NUMBER OFF PROTOCOL TREATMENT
REASON OFF TREATMENT
145 133 12
Treatment completed as planned 138 127 11
Adverse Event or side effects 1 1 0
Refusal unrelated to adverse event 1 1 0
Other - not protocol specified 0 0 0
Reason under review 5 4 1
MAJOR PROTOCOL DEVIATIONS 2 2 0
APRIL 26 - 29, 2017 SWOG LYMPHOMA 14
S1001/II
Number of Patients with a Given Type and Grade of Adverse Event
PET-Directed Therapy
Adverse Events Unlikely or Not Related to Treatment Excluded
Data as of February 23, 2017
Continued R-CHOP
(n=134)
Grade
IFRT + Zevalin
(n=12)
Grade
ADVERSE EVENTS 0 1 2 3 4 5 0 1 2 3 4 5
ALT increased 122 11 0 1 0 0 11 1 0 0 0 0
AST increased 127 7 0 0 0 0 11 1 0 0 0 0
Abdominal pain 133 0 0 1 0 0 11 1 0 0 0 0
Alkaline phosphatase increased 133 1 0 0 0 0 12 0 0 0 0 0
Allergic rhinitis 133 0 1 0 0 0 12 0 0 0 0 0
Alopecia 109 8 17 0 0 0 9 1 2 0 0 0
Anemia 86 33 13 2 0 0 7 3 1 1 0 0
Anorexia 130 2 1 1 0 0 9 2 1 0 0 0
Anxiety 133 1 0 0 0 0 11 0 1 0 0 0
Arthralgia 130 3 1 0 0 0 12 0 0 0 0 0
Arthritis 133 1 0 0 0 0 12 0 0 0 0 0
Blurred vision 133 1 0 0 0 0 11 1 0 0 0 0
Bone pain 132 2 0 0 0 0 12 0 0 0 0 0
Chills 133 1 0 0 0 0 11 1 0 0 0 0
Constipation 127 7 0 0 0 0 11 1 0 0 0 0
Cough 130 3 1 0 0 0 10 2 0 0 0 0
Creatinine increased 131 2 1 0 0 0 12 0 0 0 0 0
Dehydration 134 0 0 0 0 0 11 0 1 0 0 0
Depression 134 0 0 0 0 0 11 0 1 0 0 0
Dermatitis radiation 134 0 0 0 0 0 10 2 0 0 0 0
Diarrhea 129 5 0 0 0 0 11 1 0 0 0 0
Dizziness 134 0 0 0 0 0 11 1 0 0 0 0
Dry mouth 131 3 0 0 0 0 10 0 2 0 0 0
Dry skin 132 2 0 0 0 0 12 0 0 0 0 0
Dysgeusia 128 3 3 0 0 0 11 0 1 0 0 0
Dyspepsia 132 2 0 0 0 0 11 1 0 0 0 0
Dysphagia 134 0 0 0 0 0 9 2 1 0 0 0
Dyspnea 128 4 2 0 0 0 12 0 0 0 0 0
Ear pain 133 1 0 0 0 0 12 0 0 0 0 0
Edema limbs 131 3 0 0 0 0 12 0 0 0 0 0
Ejection fraction decreased 133 0 0 1 0 0 12 0 0 0 0 0
Esophagitis 134 0 0 0 0 0 11 0 1 0 0 0
Eye disorders - Other, specify 133 1 0 0 0 0 12 0 0 0 0 0
Eye pain 133 1 0 0 0 0 12 0 0 0 0 0
Fall 133 0 0 1 0 0 12 0 0 0 0 0
Fatigue 80 44 9 1 0 0 6 5 1 0 0 0
Febrile neutropenia 132 0 0 2 0 0 12 0 0 0 0 0
Fever 132 2 0 0 0 0 12 0 0 0 0 0
Flu like symptoms 133 1 0 0 0 0 12 0 0 0 0 0
GERD 129 4 1 0 0 0 12 0 0 0 0 0
Gastric ulcer 133 1 0 0 0 0 12 0 0 0 0 0
Gastritis 133 1 0 0 0 0 11 1 0 0 0 0
Gen disorders/admin site cond 133 1 0 0 0 0 12 0 0 0 0 0
Generalized muscle weakness 131 1 2 0 0 0 11 1 0 0 0 0
APRIL 26 - 29, 2017 SWOG LYMPHOMA 15
S1001/II
Continued R-CHOP
(n=134)
Grade
IFRT + Zevalin
(n=12)
Grade
ADVERSE EVENTS 0 1 2 3 4 5 0 1 2 3 4 5
Glucose intolerance 133 0 1 0 0 0 12 0 0 0 0 0
Gum infection 133 1 0 0 0 0 12 0 0 0 0 0
Headache 133 1 0 0 0 0 12 0 0 0 0 0
Hearing impaired 133 1 0 0 0 0 12 0 0 0 0 0
Hot flashes 130 3 1 0 0 0 12 0 0 0 0 0
Hypercalcemia 133 1 0 0 0 0 12 0 0 0 0 0
Hyperglycemia 128 3 2 1 0 0 11 1 0 0 0 0
Hyperhidrosis 133 1 0 0 0 0 11 1 0 0 0 0
Hyperkalemia 132 2 0 0 0 0 12 0 0 0 0 0
Hypertension 128 4 0 2 0 0 12 0 0 0 0 0
Hyperuricemia 133 1 0 0 0 0 12 0 0 0 0 0
Hypoalbuminemia 131 3 0 0 0 0 12 0 0 0 0 0
Hypocalcemia 131 2 0 1 0 0 12 0 0 0 0 0
Hypoglycemia 133 1 0 0 0 0 12 0 0 0 0 0
Hypokalemia 128 3 1 2 0 0 12 0 0 0 0 0
Hypomagnesemia 133 1 0 0 0 0 11 1 0 0 0 0
Hyponatremia 131 2 0 1 0 0 12 0 0 0 0 0
Hypotension 133 0 0 1 0 0 12 0 0 0 0 0
Hypoxia 132 0 0 1 0 1 12 0 0 0 0 0
Infections/infestations-Other 132 0 2 0 0 0 12 0 0 0 0 0
Insomnia 132 2 0 0 0 0 10 0 2 0 0 0
Irregular menstruation 133 1 0 0 0 0 12 0 0 0 0 0
Laryngeal edema 134 0 0 0 0 0 11 1 0 0 0 0
Leukocytosis 133 0 0 1 0 0 12 0 0 0 0 0
Localized edema 133 0 1 0 0 0 12 0 0 0 0 0
Lymphedema 133 0 1 0 0 0 12 0 0 0 0 0
Lymphocyte count decreased 86 21 18 9 0 0 8 2 0 2 0 0
Malaise 133 0 1 0 0 0 12 0 0 0 0 0
Memory impairment 133 1 0 0 0 0 12 0 0 0 0 0
Mucositis oral 128 5 1 0 0 0 11 0 1 0 0 0
Muscle weakness lower limb 133 1 0 0 0 0 12 0 0 0 0 0
Muscle weakness upper limb 133 1 0 0 0 0 12 0 0 0 0 0
Myalgia 132 2 0 0 0 0 10 1 1 0 0 0
Nail discoloration 132 2 0 0 0 0 12 0 0 0 0 0
Nail loss 133 1 0 0 0 0 12 0 0 0 0 0
Nail ridging 131 3 0 0 0 0 12 0 0 0 0 0
Nasal congestion 132 0 2 0 0 0 12 0 0 0 0 0
Nausea 121 13 0 0 0 0 10 2 0 0 0 0
Neoplasms, all 133 1 0 0 0 0 12 0 0 0 0 0
Nervous sys disorders-Other 133 0 0 1 0 0 11 1 0 0 0 0
Neutrophil count decreased 114 2 5 4 9 0 7 1 2 1 1 0
Oral pain 132 1 1 0 0 0 12 0 0 0 0 0
Pain 131 3 0 0 0 0 12 0 0 0 0 0
Pain in extremity 130 2 2 0 0 0 11 0 1 0 0 0
Paresthesia 132 2 0 0 0 0 12 0 0 0 0 0
Peripheral motor neuropathy 132 2 0 0 0 0 12 0 0 0 0 0
Peripheral sensory neuropathy 109 22 2 1 0 0 10 2 0 0 0 0
Pharyngitis 133 0 1 0 0 0 11 0 1 0 0 0
Phlebitis 133 0 1 0 0 0 12 0 0 0 0 0
Platelet count decreased 117 13 0 2 2 0 8 0 1 2 1 0
Productive cough 133 1 0 0 0 0 12 0 0 0 0 0
APRIL 26 - 29, 2017 SWOG LYMPHOMA 16
S1001/II
Continued R-CHOP
(n=134)
Grade
IFRT + Zevalin
(n=12)
Grade
ADVERSE EVENTS 0 1 2 3 4 5 0 1 2 3 4 5
Pruritus 132 2 0 0 0 0 12 0 0 0 0 0
Rash acneiform 133 1 0 0 0 0 12 0 0 0 0 0
Renal calculi 133 1 0 0 0 0 12 0 0 0 0 0
Resp/thoracic/mediastinal ds 132 1 0 0 1 0 12 0 0 0 0 0
Secondary Leukemia 133 0 0 0 1 0 12 0 0 0 0 0
Sinus bradycardia 133 1 0 0 0 0 12 0 0 0 0 0
Sinus tachycardia 132 2 0 0 0 0 12 0 0 0 0 0
Skin infection 131 1 1 1 0 0 12 0 0 0 0 0
Skin/subq tissue ds-Other 133 1 0 0 0 0 12 0 0 0 0 0
Small intestine infection 133 0 0 1 0 0 12 0 0 0 0 0
Sore throat 133 0 1 0 0 0 11 1 0 0 0 0
Telangiectasia 133 1 0 0 0 0 12 0 0 0 0 0
Thromboembolic event 133 0 0 1 0 0 12 0 0 0 0 0
Upper respiratory infection 131 0 3 0 0 0 12 0 0 0 0 0
Urinary frequency 133 1 0 0 0 0 12 0 0 0 0 0
Urinary tract infection 132 0 2 0 0 0 11 0 1 0 0 0
Urine discoloration 133 1 0 0 0 0 12 0 0 0 0 0
Voice alteration 133 0 1 0 0 0 12 0 0 0 0 0
Vomiting 133 1 0 0 0 0 12 0 0 0 0 0
Weight gain 131 2 1 0 0 0 12 0 0 0 0 0
Weight loss 131 1 1 1 0 0 10 2 0 0 0 0
White blood cell decreased 100 17 4 8 5 0 7 1 2 2 0 0
MAX. GRADE ANY ADVERSE EVENT 13 36 51 21 12 1 1 5 2 2 2 0
APRIL 26 - 29, 2017 SWOG LYMPHOMA 17
S1204
S1204 Surveillance
A Sero-Epidemiologic Survey and Cost-Effectiveness Study of Screening for
Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV) and
Hepatitis C Virus (HCV) Among Newly Diagnosed Cancer Patients
Study Chairs:
S Ramsey, D Hershman
Statisticians:
J Unger, K Arnold
Data Coordinator:
M Yee
Date Activated:
08/29/2013
Date Closed:
02/15/2017
Objectives Among newly diagnosed cancer patients presenting
to SWOG-affiliated community and academic
oncology clinics, estimate the prevalence of human
immunodeficiency virus (HIV), hepatitis B (HBV),
and hepatitis C (HCV) infection.
Evaluate known sociodemographic, clinical, and
behavioral factors that are significantly associated
with previously undiagnosed HIV, HBV, and/or
HCV infection in a population of people with newly
diagnosed cancer
Among patients who are identified as having HIV,
HBV, and/or HCV, evaluate the timing and type of
treatments received, both for the viral infections and
the cancers.
Evaluate type and rate of cancer treatment-related
adverse events in patients with HIV, HBV, and/or
HCV infection.
Determine the cost-effectiveness of (1) routine,
universal screening and (2) risk factor-directed
screening of newly diagnosed cancer patients for HIV,
HBV and/or HCV versus current care.
Patient Population Patients must be presenting for evaluation or
treatment for the first diagnosis of a new solid or
hematologic cancer malignancy. Confirmed diagnosis
date must be within 120 days prior to first clinic visit
as a newly diagnosed cancer patient at the registering
clinic. Patients presenting for "second opinions" of
confirmed malignancies are eligible, including those
who have started cancer treatment at other facilities.
Patients must be registered within 90 days after their
first clinic visit. Patients must not have been
diagnosed with a malignancy other than the current
malignancy within the past five years, with the
exception of basal cell or squamous cell skin cancer,
in situ cervical cancer, or in situ breast cancer.
Patients must have no evidence of disease for a prior
malignancy for at least five years prior to
randomization except as noted above.
Patients must be 18 years of age or older. Patients
must have had their blood drawn for viral status
testing for HIV, HBV and HCV or provide
acceptable viral status documentation prior to
registration, as defined in the protocol. Note that
patients must have blood drawn for testing prior to
registration for any of the three viruses not covered
by the documentation. Patients are allowed to
participate in other clinical trials.
Accrual Goals A total of 3,061 patients will be accrued to achieve
3,000 eligible patients.
Summary Statement For the current status of this study, please refer to the
Cancer Care Delivery chapter.
APRIL 26 - 29, 2017 SWOG LYMPHOMA 18
S1608/II
S1608 Phase II
Coordinating Group: SWOG
Randomized Phase II Trial in Early Relapsing or Refractory Follicular
Lymphoma
Participants:
SWOG, CTSU (Supported by Alliance and ECOG-ACRIN)
Study Chairs:
P Barr, B Link (Alliance), C Flowers (ECOG-ACRIN)
Statisticians:
H Li, M LeBlanc
Data Coordinator:
I Syquia
SCHEMA
Objectives To compare the complete response rate at 6 cycles
after randomization as defined by centrally read
PET/CT (integral biomarker) of two targeted
therapeutic regimens (obinutuzumab + TGR-1202 or
obinutuzumab + lenalidomide) with obinutuzumab +
CHOP in patients with early relapsing or refractory
follicular lymphoma.
To validate the prognostic association of the m7-
FLIPI model, demonstrating that the population of
follicular lymphoma patients who respond poorly to
chemoimmunotherapy are enriched for having a
high-risk m7-FLIPI score, and that the score is
associated with progression-free survival (integrated
biomarker).
To estimate the 30 month sustained complete
response rate (CR30) defined by centrally read
PET/CT with each of the regimens in this early
relapsing or refractory follicular lymphoma
population.
R
A
N
D
O
M
I
Z
A
T
I
O
N
TGR-1202 + Obinutuzumab
Lenalidomide + Obinutuzumab
CHOP + Obinutuzumab
APRIL 26 - 29, 2017 SWOG LYMPHOMA 19
S1608/II
To estimate best response at 12 cycles of therapy,
progression-free survival, duration of response, and
overall survival with each of the combinations in
early relapsing or refractory follicular lymphoma.
To evaluate the adverse effects of each of the
regimens in early relapsing or refractory follicular
lymphoma.
To evaluate the predictive performance of non-
invasive genotyping (m7-FLIPI in circulating tumor
DNA) of plasma at study entry relative to standard
tumor genotyping (m7-FLIPI) of formalin-fixed
paraffin-embedded tumor tissue.
To evaluate the association between the detection of
active lymphoma by PET/CT and the detection of
circulating tumor DNA in plasma at baseline, after 6
and 12 cycles, and at 30 months after initiation of
study therapy
Patient Population Patients must have follicular lymphoma (Grade I, II
or IIIa) confirmed at initial diagnosis and at relapse
with identifiable FDG avid disease on PET/CT.
Patients must not have involvement with large cell
lymphoma. Patients must have failed to achieve a
complete remission, or must have relapsed within
two years after completing one line of bendamustine-
containing chemoimmunotherapy. Patients must
have the components of Follicular Lymphoma
International Prognostic Index (FLIPI) available from
diagnosis and at time of registration. Patients must
not have clinical evidence of central nervous system
involvement by lymphoma.
Patients must have received at least three cycles
of bendamustine as first line therapy. Patients
may have additionally received maintenance anti-
CD-20 antibody based therapy or consolidative
radioimmunotherapy within two years of completing
the bendamustine therapy. Patients must have
completed systemic therapy at least 21 days prior to
registration or completed radioimmunotherapy at
least 84 days prior to registration. Patients must have
recovered from all treatment related toxicities prior to
registration. Patients must not have had prior
anthracycline based therapy, or any prior treatment
with any PI3K inhibitor or lenalidomide. Relapsed
patients must not have received any intervening
chemotherapy. Patients must be able and willing to
take prophylaxis as listed in the protocol.
Patients must be at least 18 years of age and have a
Zubrod performance status of 0-2. Patients must have
adequate renal, hepatic, cardiac and hematologic
function. Patients with Hepatitis B virus infection, or
Hepatitis C virus infection, or known HIV infection
are eligible with restrictions. Females of childbearing
potential (FCBP) must have a negative serum or
urine pregnancy test with a sensitivity of at least 25
mIU/mL within 10 - 14 days prior to registration.
Stratification/Descriptive Factors Patient randomization will be stratified according to
the following factors: (1) previous receipt of
maintenance therapy: yes vs no; and (2) refractory
status: lack of CR after completing first line
bendamustine-containing chemoimmunotherapy vs
disease relapse within two years of completing first
line bendamustine-containing chemoimmunotherapy.
Accrual Goals The accrual goal for this study is 150 patients to
achieve 135 eligible patients. Interim analyses are
planned after response data for six cycles of
treatment are available for the first half of patients on
each arm.
APRIL 26 - 29, 2017 SWOG LYMPHOMA 20
EAY131/II
EAY131 Master Protocol / Phase II
Coordinating Group: ECOG-ACRIN
NCI-MATCH: Molecular Analysis for Therapy Choice
Participants:
ECOG-ACRIN, CTSU
Study Chairs:
K Flaherty (ECOG-ACRIN), P O'Dwyer (ECOG-ACRIN),
A Chen (NCI), B Conley (NCI), V Villalobos (SWOG)
Date Activated:
08/12/2015
SCHEMA
Objectives To evaluate the proportion of patients with objective
response (OR) to targeted study agent(s) in patients
with advanced refractory
cancers/lymphomas/multiple myeloma.
To evaluate the proportion of patients alive and
progression free at six months of treatment with
targeted study agent in patients with advanced
refractory cancers/lymphomas/multiple myeloma.
To evaluate the time until death or disease
progression.
To identify potential predictive biomarkers beyond
the genomic alteration by which treatment is assigned
or resistance mechanisms using additional genomic,
RNA protein and imaging-based assessment
platforms.
To assess whether radiomic phenotypes obtained
from pre-treatment imaging and changes from pre-
through post-therapy imaging can predict objective
response and progression-free survival and to
evaluate the association between pre-treatment
radiomic phenotypes and targeted gene mutation
patterns of tumor biopsy specimens.
Patient Population Patients must have histologically documented solid
tumors or histologically confirmed diagnosis of
lymphoma or multiple myeloma that has progressed
following at least one line of standard systemic
therapy and/or for whose disease no standard
treatment exists that has been shown to prolong
Screening
Registration
Tissue Submission for
Molecular Profiling
No Molecular Profile
of Interest
Treatment for
Molecular Profile of
Interest
*Upon progression or inability to tolerate protocol treatment, patients may be re-screened for additional molecular profiles
of interest and corresponding protocol treatment.
Off Study
Toxicity or
Progression*
APRIL 26 - 29, 2017 SWOG LYMPHOMA 21
EAY131/II
survival. Patients must have measurable disease and
meet one of the criteria in the protocol regarding
tissue procurement.
Patients must not currently be receiving any other
investigational agents. Any prior therapy,
radiotherapy (except palliative radiation therapy of
30 Gy or less), or major surgery must have been
completed at least four weeks prior to treatment on
NCI-MATCH and patient must be recovered from
adverse events due to prior therapy (except alopecia
and lymphopenia). Palliative radiation therapy must
have been completed at least two weeks prior to
enrollment on a NCI-MATCH treatment subprotocol,
and patient must have recovered from any adverse
events of this therapy. Patients with brain metastases
or primary brain tumors must have completed
treatment , surgery, or radiation therapy at least four
weeks prior to start of treatment. Patients must not
require the use of full dose coumarin-derivative
anticoagulants. Factor X inhibitors are permitted.
Patients may receive non-protocol treatment after
biopsy (if clinically indicated) until they receive
notification of results, but patients may not enroll in
another investigational study during this time and the
therapy cannot be an arm in this trial.
Patients must be at least 18 years of age, have an
ECOG performance status of 0 or 1 and must be able
to swallow tablets. Patients must have adequate
hematologic, hepatic, renal, cardiac and marrow
function. Patients must not have any uncontrolled
intercurrent illness. HIV-positive patients are eligible
provided they meet protocol criteria. Each
subprotocol will have additional eligibility criteria
that will be outlined in Section 2.0 of the agent-
specific subprotocol.
Accrual Goals The target screening accrual for this study is
approximately 3,000 patients, with the goal of
accruing 35 patients in each treatment subprotocol. If
after screening 500 patients, the total number of
patients with actionable tumor alteration (therefore
qualifying for treatment) is below 50, results will be
presented to the steering committee for consideration
of terminating the trial. Within any given subprotocol,
if rate of enrollment is such that it is unlikely accrual
can reach 25 patients by the time the overall study
screening accrual goal is met, and if 13 patients have
been treated and no responses have been observed,
then the steering committee may consider terminating
accrual in that subgroup due to lack of feasibility.
After 500 patients are screened, the study design will
be reassessed to assure its appropriateness. An
interim analysis of the assay results will be
performed after biopsies from approximately the first
200 patients are processed.
Summary Statement This study activated on January 26, 2015, with 10
subprotocols included in the activation. Only sites
utilizing the CIRB as their IRB of record are able to
participate in the trial. The study was temporarily
closed to accrual on November 11, 2015, after rapid
accrual of 795 patients to the screening step in only
three months, including 119 SWOG registrations.
This pause in patient enrollment for assessment of
study design appropriateness was lifted on May 31,
2016, when this study reopened to enrollment with an
additional 14 new subprotocols. As of November 16,
2016, accrual to subprotocol N has been suspended
due to drug supply shortage.
ECOG-ACRIN reported a total of 4,121 screened
patients and 368 molecularly matched patients as of
December 31, 2016. This includes 512 screened and
46 molecularly matched SWOG registrations. The
complete Spring 2016 summary of this study from
ECOG-ACRIN is available on the SWOG web site.
ECOG-ACRIN Cancer Research Group E1412
Study Progress and Safety Report Spring 2016
Page 1
E1412 RANDOMIZED PHASE II STUDY OF LENALIDOMIDE R-CHOP (R2CHOP) VS R-
CHOP (RITUXIMAB, CYCLOPHOSPHAMIDE, DOXORUBICIN, VINCRISTINE, AND
PREDNISONE) IN PATIENTS WITH NEWLY DIAGNOSED DIFFUSE LARGE B CELL
LYMPHOMA
Sponsor(s)
Coordinating Group ECOG-ACRIN
Chairperson(s) Dr. Grzegorz Nowakowski
Therapeutic Statistician Dr. Fangxin Hong
Imaging Statistician Dr. Fenghai Duan
Data Specialist Jannett Garrido
Phase of Study II
Type of Study Therapeutic
Committee Lymphoma
Accrual Objective 345 Patients
Participating Groups ECOG-ACRIN
DCP Treatment Credit 1.0
NSC# 10023, 26271, 67574, 687451, 703813, 725961
Clinicaltrials.gov Study ID NCT01856192
Study Status Open to Accrual
Date Proposed June 8, 2012
Date Activated August 27, 2013
Date Suspended May 22, 2015
Date Reactivated October 13, 2015
SCHEMA
ECOG-ACRIN Cancer Research Group E1412
Study Progress and Safety Report Spring 2016
Page 2
Purpose of the Study
Primary Endpoint (1) Progression-free survival (PFS) Secondary Endpoints (1) Response rate (RR) (2)
CR rate as defined by PET-CT criteria (3) Overall survival (OS) Correlative Endpoints (1) Impact of
DLBCL molecular subtype on outcome. (2) Interim PET scan results in relation to treatment outcome.
Study Population
Adult patients (age >/= 18) with untreated, histologically confirmed DLBCL expressing CD20 antigen,
stages IIB or II bulky measurable disease, ECOG PS 0-2, adequate organ function, able to receive aspirin
therapy. Pregnant or nursing women are excluded.
Summary of Study Design
In the revised design, a total of 345 patients will be enrolled to generate a total of 283 eligible DLBCL
cases, of which 102 cases are ABC-DLBCL. Patients will be randomized at 1:1 ratio to the control arm
(RCHOP) and the experimental arm (R2CHOP), stratified on IPI (2-3 vs. 4-5), age (<60 yrs. Vs >60 yrs).
The primary objective is to determine whether R2CHOP improves progression-free survival (PFS)
compared to RCHOP. A cure rate model was used for the PFS endpoint. It is expected that 2-year PFS
rate will be 64%, and cure rate is about 60% for the RCHOP arm. Assuming exponential distribution for
the PFS in the non-cure group, this translates into a median of 7.2 months (monthly failure rate of 0.096)
in the non-cure group. With a total accrual of 283 evaluable (eligible and treated) patients and total
information of 89 failures (additional 24 months follow-up); the study will have 89% to detect a 13%
increase in 2-year PFS rate from 64% to 77% in the R2CHOP arm, at one-sided 0.1 significance
level.With proportional hazard rate assumption, this difference corresponds to a hazard ratio of 0.59 and a
41% reduction in the PFS failure rate. A subset analysis within patients with ABC subtype is planned.
With 102 eligible ABC patients, the study will have 81% power to detect an 18% improvement to 74% 2-
year PFS rate for patients with ABC subtype, at one-sided 0.125 significance level. With proportional
hazard rate assumption, this difference corresponds to a hazard ratio of 0.52 and a 48% reduction in the
PFS failure rate. A correlative study of the results of interim PET scans, performed at prior to treatment,
prior to cycle 4 and after cycle 6 is also planned. These standard of care images will be archived at the
ACRIN Core PET Laboratory, and will be read centrally to examine these aims: 1) to evaluate the
association between a binary score of baseline SUV and PFS; 2) to evaluate the association of a binary
score of percent change in SUV from baseline to post-cycle 3; and 3) to compare percent change in SUV
from post-cycle 3 to baseline between the R2CHOP and RCHOP arims. Additional exploratory aims will
also be analyzed based on SUVs.
Progress to Date
This study was activated on August 27, 2013, suspended on May 22, 2015 after reaching its initial
accrual goal, and was reopened on October 13, 2015. A total of 244 patients have enrolled to the study as
of February 15, 2016. Accrual by ECOG-ACRIN institution and accrual by group are given in Tables 1a
and 1b, respectively. Projected accrual is listed in Table 1c. Expected cumulative accrual and actual
cumulative accrual are shown in Figure 1. Patient status as of February 15, 2016 is listed in Table 2.
Baseline patient demographic variables are listed in Table 3. Record status (number of forms due and
received) is listed in Table 4. Reasons off treatment are summarized in Table 5. Toxicity data is available
on 193 patients and incidence (hematologic toxicities included) is summarized in Table 6a. Grade 5
toxicity was observed in 5 patients. Off-treatment (treatment-related) toxicity is available on 175 patients
and incidence is presented in Table 6b. Nine lethal adverse events are listed in Table 7. One primary
secondary cancer was observed on Arm A (Table 8). Imaging status as of February 15, 2016 is listed in
Table 9.
ECOG-ACRIN Cancer Research Group E1412
Study Progress and Safety Report Spring 2016
Page 3
Table 1a. Accrual by ECOG-ACRIN Institution
Institution Name Step 0 Step 1
Aurora NCORP 0 4
Baystate Medical Center 0 1
Cancer Research Consortium of West Michigan NCORP 1 0
Cancer Research for the Ozarks NCORP 0 2
Carle Cancer Center NCORP 0 2
Case Western Reserve University 1 6
Colorado Cancer Research Program NCORP 0 3
Columbus NCORP 0 2
Dartmouth Hitchcock Medical Center 2 0
Delaware/Christiana Care NCORP 0 6
Emory University/Winship Cancer Institute 3 8
Essentia Health NCORP 0 1
Fox Chase Cancer Center 0 11
Froedtert and the Medical College of Wisconsin 0 3
Geisinger Cancer Institute NCORP 1 0
Georgia NCORP 0 1
Heartland Cancer Research NCORP 1 12
Indiana Univ/Melvin and Bren Simon Cancer Center 0 4
Iowa-Wide Oncology Research Coalition NCORP 0 5
Johns Hopkins Univ/Sidney Kimmel Cancer Center 0 10
Laura and Issac Perlmutter Ca Ctr at NYU Langone 0 1
Mayo Clinic 6 13
Metro Minnesota Community Oncology Res Consortium 1 8
Michigan Ca Res Consortium NCORP 0 12
Montana Cancer Consortium NCORP 1 0
Montefiore MU NCORP 0 2
Nevada Cancer Research Foundation NCORP 0 1
New Mexico MU NCORP 1 1
Northwestern University 2 2
Penn State Milton S Hershey Medical Center 1 3
Saint Luke's University Hospital-Bethlehem Campus 1 4
Sanford NCORP of the North Central Plains 1 5
Stanford Cancer Institute 1 1
Summa Akron City Hospital/Cooper Cancer Center 0 1
Thomas Jefferson University Hospital 0 7
Tufts Medical Center 0 1
UT Southwestern/Simmons Cancer Center-Dallas 0 8
University of Massachusetts Medical School 0 1
University of Michigan Comprehensive Cancer Center 1 1
University of Pennsylvania/Abramson Cancer Center 0 2
University of Wisconsin Hospital and Clinics 1 6
Vanderbilt University/Ingram Cancer Center 2 4
Wichita NCORP 2 3
Wisconsin NCORP 1 5
Total 31 173
ECOG-ACRIN Cancer Research Group E1412
Study Progress and Safety Report Spring 2016
Page 4
Table 1b. Accrual by Group
ECOG-ACRIN 31 173
SWOG 3 28
ALLIANCE 11 32
NRG 3 11
Total 48 244
Table 1c. Projected Accrual
Accrual goal 345
Planned accrual rate 144/yr
Accrual to date 244
Annual accrual rate
Overall 117/yr
Projected date of closure March 2017
ECOG-ACRIN Cancer Research Group E1412
Study Progress and Safety Report Spring 2016
Page 5
Table 2. Patient Status as of February 15, 2016
Cases Entered 244
Ineligible 0
Never Started Assigned Therapy 6
Reason for not starting assigned therapy (n=6)
Patient was hospitalized the day after registration (14024);
Patient withdrawal/refusal before beginning protocol therapy (14117, 14186);
Death before beginning protocol therapy (14196).
(14172, 14219)
Table 3. Demographics
Variable Level Arm A (n=121) Arm B (n=123) Total (n=244)
Sex Male 74 (61.2) 70 (56.9) 144 (59.0)
Female 47 (38.8) 53 (43.1) 100 (41.0)
Race White 111 (93.3) 104 (89.7) 215 (91.5)
African-American 5 (4.2) 9 (7.8) 14 (6.0)
Asian 3 (2.5) 3 (2.6) 6 (2.6)
Unknown/Unreported 2 7 9
Ethnicity Hispanic 4 (3.5) 5 (4.3) 9 (3.9)
Non-Hispanic 110 (96.5) 110 (95.7) 220 (96.1)
Unknown/Missing 7 8 15
Age Median 66 65 65
Minimum 23 22 22
Maximum 85 91 91
Table 4. Record Status
Form Name Forms Due Forms Received %
Demography 243 243 100.0
Patient Characteristics 243 238 97.9
Treatment Agent: Cyclophosphamide 1216 1198 98.5
Treatment Agent: Doxorubicin 1216 1198 98.5
Treatment Agent: Lenalidomide 608 596 98.0
Treatment Agent: Prednisone 1216 1179 97.0
Treatment Agent: Rituximab 1216 1198 98.5
Treatment Agent: Vincristine 1216 1198 98.5
Adverse Event Form 1216 1152 94.7
Disease Follow-Up Status Form 1800 1759 97.7
Off Treatment 209 206 98.6
ECOG-ACRIN Cancer Research Group E1412
Study Progress and Safety Report Spring 2016
Page 6
Table 5. Reasons Off Treatment
(Includes all patients who started treatment and
for whom off-treatment data have been received)
Reasons N %
Adverse event/side effects/complications 8 3.9
Alternative therapy 2 1.0
Death on study 7 3.4
Disease progression, relapse during active treatment 5 2.4
Other 6 2.9
Patient withdrawal/refusal after beginning protocol therapy 2 1.0
Treatment completed per protocol criteria 176 85.0
Total off treatment 206 99.5
Table 6a. Treatment-Related Toxicities
Toxicity Type
Treatment Arm
A (n=107) B (n=110)
Grade Grade
3 4 5 3 4 5
(%) (%) (%) (%) (%) (%)
Tinnitus 1 - - - - -
Anemia 21 5 - 21 2 -
Febrile neutropenia 18 3 - 7 - 1
Leukocytosis - - - - 1 -
Left ventricular systolic dysfunction 2 - - - - -
Fatigue 10 - - 6 - -
Fever 1 - - 1 - -
Edema limbs - - - 1 - -
Infusion related reaction 1 1 - - - -
Pruritus 1 - - - - -
Rash maculo-papular 1 - - - - -
Abdominal pain 1 - - - - -
Colonic obstruction 1 - - - - -
Diarrhea 7 - - - - -
Enterocolitis 1 - - - - -
Gastric perforation - - - 1 - -
Gastrointestinal disorders - Other, specify - - - 1 - -
Mucositis oral 2 - - 1 - -
Nausea 2 - - 1 - -
Vomiting 2 - - - - -
Lower gastrointestinal hemorrhage 1 - - - - -
Infections and infestations - Other, specify 2 - - - - -
Sepsis - 3 - - 2 2
Skin infection 2 - - - - -
Upper respiratory infection 1 - - - - -
Urinary tract infection 5 - - 2 - -
Enterocolitis infectious 1 - - - - -
ECOG-ACRIN Cancer Research Group E1412
Study Progress and Safety Report Spring 2016
Page 7
Table 6a. Treatment-Related Toxicities
Toxicity Type
Treatment Arm
A (n=107) B (n=110)
Grade Grade
3 4 5 3 4 5
(%) (%) (%) (%) (%) (%)
Lung infection 5 1 - 2 - 1
Pleural infection - - - 1 - -
Anorectal infection 1 - - - - -
Soft tissue infection 1 - - - - -
Fall - - - 1 - -
Alanine aminotransferase increased - - - 1 - -
Alkaline phosphatase increased 1 - - - - -
Creatinine increased 1 - - - - -
Lymphocyte count decreased 20 11 - 19 8 -
Neutrophil count decreased 9 49 - 13 43 -
Platelet count decreased 15 16 - 5 8 -
White blood cell decreased 11 29 - 9 22 -
Ejection fraction decreased 1 - - 1 - -
Anorexia 2 - - - - -
Dehydration 5 - - 3 - -
Hyperglycemia 1 - - - - -
Hypoalbuminemia 1 - - - - -
Hypocalcemia 2 - - 1 - -
Hypokalemia 7 - - 1 - -
Hyponatremia 5 - - 3 - -
Hypophosphatemia 4 - - 2 - -
Musculoskeletal and connective tissue disorder - Other, specify 1 - - - - -
Pain in extremity - - - 1 - -
Generalized muscle weakness 7 - - 2 - -
Dizziness 1 - - - - -
Peripheral sensory neuropathy 1 - - 1 - -
Syncope 2 - - 2 - -
Confusion 1 - - - - -
Delirium - - - 1 - -
Insomnia - - - 2 - -
Hiccups 1 - - - - -
Pleural effusion - - - 1 - -
Pneumonitis 1 - 1 - - -
Productive cough 1 - - - - -
Respiratory failure - 1 - - - -
Renal calculi 1 - - - - -
Acute kidney injury 1 - - - - -
Hypertension - - - 1 - -
Hypotension 2 - - 2 - -
Thromboembolic event 3 - - 1 - -
Vascular disorders - Other, specify 1 - - - - -
WORST DEGREE 22 53 1 17 45 4
ECOG-ACRIN Cancer Research Group E1412
Study Progress and Safety Report Spring 2016
Page 8
Table 6b Treatment-Related later (off treatment )Toxicities
Toxicity Type
Treatment Arm
OT (n=175)
Grade
3 4 5
(%) (%) (%)
Left ventricular systolic dysfunction 1 - -
Diarrhea 1 - -
Sepsis - - 1
Lymphocyte count decreased 1 - -
Neutrophil count decreased 1 1 -
White blood cell decreased 1 1 -
Ejection fraction decreased 1 - -
Dyspnea 1 - -
WORST DEGREE 3 1 1
Table 7. Lethal Adverse Events (regardless of treatment relation)
Case # Arm Description of Event
14039 B Death after cycle 6, last chemo 8/15/14. Admitted to hospital 4 months later
(12/16/14) with bilateral healthcare associated pneumonia, died 12/22 due to
sepsis/pneumonia. Reported as possibly related to treatment.
14052 B Cycle 6 day 8, weakness, neutropenic fever, UTI, pulmonary edema, elected
against aggressive treatment and discharged to hospice.
14103 B Cycle 1 day9, admitted for neutropenic fever, per report given neupogen. Blood
counts recovered, found to have pneumonia later in hospitalization, pleural
effusions,. Tried BiPAP, but declined intubation and died of respiratory failure,
on comfort measures. Reported as probable.
14129 B Cycle 2, day 19, hospitalized for neutropenic fever, blood count recovered, but
tracheoesophageal fistula documented by barium swallow with barium
aspiration, of note patient had exredodal lung involvement, patient not a
candidate for surgical repair, did not want stent, elected hospice. Death reported
as unrelated to treatment.
14130 B Cycle 1, day 5 with neutropenic fever, of note received prophylactic neulasta,
colitis and sepsis, had emergent surgery. Toxic megacolon, died after 5 day
hospitalization. Reported as probable.
14131 B Death after cycle 3, day 17, sudden death in patient with h/o CAD; asymptotic
the day before, sudden death during the night, no autopsy. Reported as unrelated
to treatment, definite to cardiac arrest.
14174 A Lung infection and febrile neutropenia followed by acute respiratory failure with
hypoxia. Patient died due to uncontrolled pneumonia
14195 B Sepsis secondary to proteus bacteremia and UTI. Possibly treatment related.
14214 A Sudden death NOS
ECOG-ACRIN Cancer Research Group E1412
Study Progress and Safety Report Spring 2016
Page 9
Table 8. Second Primary Cancers
(By arm during which event was reported)
Site Arm A Arm B
Lung 1 -
Table 9. Imaging Status
Status of PET PET Completed PET Received at Core Lab
n % n %
All 3 PET scans 145 61% 106 44%
PET3 and PET6, but not PET0 3 1% 1 0%
PET0 and PET6, but not PET3 15 6% 15 6%
PET0 and PET3, but not PET6 30 13% 42 18%
PET6, but not PET0 or PET3 1 0% 2 1%
PET3, but not PET0 or PET6 1 0% 2 1%
PET0, but not PET3 or PET6 29 12% 24 10%
No PET scans 15 6% 47 20%
Definitions
PET0 = Pre-treatment PET scan (Baseline)
PET3 = Post-cycle 3/Pre cycle 4 PET scan
PET6 = Post-cycle 6 PET scan
NOTE: Participant(s) who never started treatment have been omitted.
ECOG-ACRIN Cancer Research Group E1411
Study Progress and Safety Report Spring 2016
Page 1
E1411 INTERGROUP RANDOMIZED PHASE II FOUR ARM STUDY IN PATIENTS WITH
PREVIOUSLY UNTREATED MANTLE CELL LYMPHOMA OF THERAPY WITH:
ARM A = RITUXIMAB+BENDAMUSTINE FOLLOWED BY RITUXIMAB
CONSOLIDATION (RB->R); ARM B =
RITUXIMAB+BENDAMUSTINE+BORTEZOMIB FOLLOWED BY RITUXIMAB
CONSOLIDATION (RBV->R), ARM C = RITUXIMAB+BENDAMUSTINE FOLLOWED
BY LENALIDOMIDE+RITUXIMAB CONSOLIDATION (RB->LR) OR ARM D =
RITUXIMAB+BENDAMUSTINE+BORTEZOMIB FOLLOWED BY
LENALIDOMIDE+RITUXIMAB CONSOLIDATION (RBV->LR)
Sponsor(s)
Coordinating Group ECOG-ACRIN
Chairperson(s) Dr. Mitchell Smith
Statistician Mr. Opeyemi Jegede
Data Specialist David Limjoco
Phase of Study II
Type of Study Therapeutic
Committee Lymphoma
Accrual Objective 332 Patients
Participating Groups ECOG-ACRIN, CALGB, SWOG, CTSU,
ALLIANCE, NRG
DCP Treatment Credit 2.0
DCP Cancer Control Credit 0.5
NSC# 138783, 681239, 687451, 703813
Clinicaltrials.gov Study ID NCT01415752
Study Status Open to Accrual
Date Proposed February 18, 2011
Date Activated May 22, 2012
Schema
ECOG-ACRIN Cancer Research Group E1411
Study Progress and Safety Report Spring 2016
Page 2
Purpose of the Study
1. Primary objectives: (1.1) To determine whether the addition of bortezomib (RBV) to an induction
regimen of rituximab-bendamustine (RB) improves progression-free survival (PFS) compared to RB alone
in patients with previously untreated mantle cell lymphoma. (1.2) To determine whether the addition of
lenalidomide to a consolidation regimen of rituximab following an induction regimen of RB or RBV
improves PFS compared to consolidation rituximab alone in this patient population. 2. Secondary
objectives: (2.1) To determine whether the addition of bortezomib to induction therapy improves the
PET-documented complete response rate compared to RB alone. (2.2) To determine the objective response
rate (ORR) for RB and RBV. (2.3) Among patients who do not have PET-documented CR at the end of
induction, to determine whether the addition of lenalidomide to consolidation therapy improves CR and
ORR compared with rituximab alone. (2.4) To determine overall survival (OS) in the treatment arms. (2.5)
To determine safety, with attention to the addition of bortezomib in the induction regimen and
lenalidomide-rituximab as consolidation therapy.
Study Population
Histologically confirmed untreated mantle cell lymphoma, ECOG PS 0-2, must have at least one objective
measurable disease parameter, must have adequate hematologic, liver and renal function, no evidence of
prior malignancy, no CNS involvement.
Summary of Study Design
The goals of the study are to determine if either bortezomib (Velcade, V) added to an induction regimen of
rituximab/ bendamustine (RB) or lenalidomide (L) added to rituximab (R) maintenance is associated with
improved outcome in patients with MCL and to identify arms suitable for evaluation in the Phase 3 setting.
332 patients, of whom 320 are expected to be eligible and to receive some protocol treatment, will be
stratified for balancing purposes according to MIPI risk status (low risk vs. intermediate vs. high risk) and
age (>/= 60 vs. < 60), and enrolled over 40 months and equally randomized to one of four arms: Arm A: RB
> R, Arm B: RBV ->R, Arm C: RB ->LR, Arm D: RBV ->LR.
Progress to Date
This study was activated on May 22, 2012. Accrual as of February 16, 2016 is 310. Tables 1a, 1b and 1c
show accrual by ECOG-ACRIN institution, accrual by group and projected accrual, respectively. Figure 1
shows cumulative accrual. Table 2 summarizes patient status as of February 16, 2016. Table 3 summarizes
demographics at study entry by arm. Record status is summarized in Table 4. Tables 5a and 5b show
off-treatment reasons for each step. Tables 6a and 6b show grade 3 and above treatment-related toxicity
data available for each step, and table 6c shows treatment-related late toxicities. Toxicity data are available
on 280 patients on step 1, 165 patients on step 2 and 47 patients for late toxicities. There were 3
treatment-related grade 5 toxicities observed in treatment step 1 and 1 treatment-related grade 5 toxicity in
step 2. These grade 5 events are listed in Table 7. List of cases with second primary cancer can be found in
Table 8. A summary of the collection of quality of life data is presented in Table 9.
Summary of New Study Design Proposal
Due to a lower than expected step 2 treatment accrual, an amendment to expand total accrual to 372, from
332, patients was proposed in February 2016. It was expected that 90% of accrued patients will proceed to
treatment step 2, but a landmark analysis conducted in December 2015, using as a cutoff the date the last
registered patient completed step 1 treatment per protocol, indicated that only 80% of accrued patients were
proceeding to treatment step 2. The revised design proposes to enroll these additional 40 patients over 4
ECOG-ACRIN Cancer Research Group E1411
Study Progress and Safety Report Spring 2016
Page 3
months with the same follow-up duration of 23 months. The original hypothesis of 37.4% reduction in the
hazard rate which corresponds to a 2-year PFS of 80% will remain the same for the new study design and
will be tested using a stratified logrank test with 1-sided Type I error of 10% for both induction and
consolidation treatments. Full information will exist for induction and consolidation treatments when 149
and 120 patients have progressed or died respectively.
Interim analysis will be conducted separately, at 25%, 50%, and 75% statistical information, for both
phases of the study (induction and consolidation) and monitored by the ECOG Data Monitoring Committee
(DMC) for early stopping for harm and futility.
Table 1a. Accrual by ECOG-ACRIN Institution
Institution Name Step 1 Step 2
Cancer Research Consortium of West Michigan NCORP 6 5
Cancer Research for the Ozarks NCORP 1 1
Carle Cancer Center NCORP 1 1
Case Western Reserve University 12 9
Catholic Health Initiatives NCORP 1 0
Colorado Cancer Research Program NCORP 7 4
Dartmouth Hitchcock Medical Center 3 0
Dayton NCORP 1 0
Delaware/Christiana Care NCORP 6 3
Essentia Health NCORP 5 2
Fox Chase Cancer Center 3 1
Fred Hutchinson Cancer Research Center 1 1
Froedtert and the Medical College of Wisconsin 7 5
Geisinger Cancer Institute NCORP 1 0
Heartland Cancer Research NCORP 2 2
Indiana Univ/Melvin and Bren Simon Cancer Center 1 1
Iowa-Wide Oncology Research Coalition NCORP 4 4
Mayo Clinic 11 6
Metro Minnesota Community Oncology Res Consortium 11 9
Michigan Ca Res Consortium NCORP 18 7
Montefiore MU NCORP 4 2
Northwestern University 7 1
Ochsner NCORP 2 2
Penn State Milton S Hershey Medical Center 1 0
Sanford NCORP of the North Central Plains 1 1
Stroger Hospital of Cook County MU NCORP 4 4
Summa Akron City Hospital/Cooper Cancer Center 0 1
Thomas Jefferson University Hospital 1 1
Tufts Medical Center 0 1
UT Southwestern/Simmons Cancer Center-Dallas 2 2
University of Pittsburgh Cancer Institute (UPCI) 2 0
University of Wisconsin Hospital and Clinics 4 2
VCU Massey Cancer Center MU NCORP 1 0
Vanderbilt University/Ingram Cancer Center 6 5
Washington University School of Medicine 7 6
Wichita NCORP 1 0
Wisconsin NCORP 7 5
Total 152 94
ECOG-ACRIN Cancer Research Group E1411
Study Progress and Safety Report Spring 2016
Page 4
Table 1b. Accrual by Group
Step 1 Step 2
ECOG-ACRIN 152 94
NCCTG 3 2
CALGB 12 5
NCIC-CTG 1 1
SWOG 74 43
NSABP 5 2
ALLIANCE 58 45
NRG 5 7
Total 310 199
Table 1c. Projected Accrual
Step 1 Step 2
Accrual goal 332
Planned accrual rate 100/yr
Accrual to date 310 199
Annual accrual rate
Overall 83/yr 53/yr
Last 6 months 112/yr 122/yr
Projected date of closure April 2016
ECOG-ACRIN Cancer Research Group E1411
Study Progress and Safety Report Spring 2016
Page 5
Table 2. Patient Status as of February 16, 2016
Step 1 Step 2
Cases Entered 310 199
Ineligible 2 0
Never Started Assigned Therapy 1 2
Reason for ineligibility Step 1:
Case 14022: Concurrent lung cancer malignancy, per study chair.
Case 14255: Baseline measurements and evaluations that confirm measurable disease
not obtained within 4 weeks of registration to the study.
Reason for not starting assigned therapy Step 1:
Case 14005: Patient ineligible
Reason for not starting assigned therapy Step 2:
Case 14060: Disease progression before protocol therapy
Case 14197: Patient withdrew before starting protocol therapy
Table 3a. Demographics Step 1
Variable Level Arm A
(n=80)
Arm B
(n=77)
Arm C
(n=77)
Arm D
(n=76)
Total
(n=310)
Sex Male 58 (72.5) 55 (71.4) 56 (72.7) 56 (73.7) 225 (72.6)
Female 22 (27.5) 22 (28.6) 21 (27.3) 20 (26.3) 85 (27.4)
Race White 72 (94.7) 74 (96.1) 69 (94.5) 68 (90.7) 283 (94.0)
African-American 3 (3.9) 1 (1.3) 0 (0.0) 4 (5.3) 8 (2.7)
Asian 1 (1.3) 2 (2.6) 4 (5.5) 1 (1.3) 8 (2.7)
Native Hawaiian 0 (0.0) 0 (0.0) 0 (0.0) 1 (1.3) 1 (0.3)
Native American 0 (0.0) 0 (0.0) 0 (0.0) 1 (1.3) 1 (0.3)
Unknown/Unreported 4 0 4 1 9
Ethnicity Hispanic 1 (1.3) 2 (2.6) 3 (4.0) 1 (1.3) 7 (2.3)
Non-Hispanic 75 (98.7) 74 (97.4) 72 (96.0) 74 (98.7) 295 (97.7)
Unknown/Missing 4 1 2 1 8
Age Median 66 69 68 67 68
Minimum 46 43 47 42 42
Maximum 83 87 90 83 90
ECOG-ACRIN Cancer Research Group E1411
Study Progress and Safety Report Spring 2016
Page 6
Table 3b. Demographics Step 2
Variable Level Arm E
(n=47)
Arm F
(n=49)
Arm G
(n=54)
Arm H
(n=49)
Total
(n=199)
Sex Male 34 (72.3) 32 (65.3) 39 (72.2) 36 (73.5) 141 (70.9)
Female 13 (27.7) 17 (34.7) 15 (27.8) 13 (26.5) 58 (29.1)
Race White 41 (91.1) 48 (98.0) 50 (96.2) 45 (93.8) 184 (94.8)
African-American 3 (6.7) 1 (2.0) 0 (0.0) 2 (4.2) 6 (3.1)
Asian 1 (2.2) 0 (0.0) 2 (3.8) 0 (0.0) 3 (1.5)
Native American 0 (0.0) 0 (0.0) 0 (0.0) 1 (2.1) 1 (0.5)
Unknown/Unreported 2 0 2 1 5
Ethnicity Hispanic 1 (2.3) 1 (2.0) 3 (5.7) 1 (2.1) 6 (3.1)
Non-Hispanic 43 (97.7) 48 (98.0) 50 (94.3) 47 (97.9) 188 (96.9)
Unknown/Missing 3 0 1 1 5
Age Median 68 70 69 66 68
Minimum 52 43 47 43 43
Maximum 83 88 90 84 90
Table 4. Record Status
Form Name Forms Due Forms Received %
Demography 310 310 100.0
Patient Characteristics 310 296 95.5
Treatment Agent: Bendamustine 1496 1440 96.3
Treatment Agent: Bortezomib 744 715 96.1
Treatment Agent: Lenalidomide 1019 926 90.9
Treatment Agent: Rituximab 3033 2927 96.5
Adverse Event Form 3485 3251 93.3
Disease Follow-up Status 3616 3397 93.9
Off Treatment (Step 1) 191 178 93.2
Off Treatment (Step 2) 118 54 45.8
Table 5a. Reasons Off-Treatment – Step 1
For Patients Not Registered to Subsequent Steps
(Includes all patients who started treatment and
for whom off-treatment data have been received)
Reasons N %
Adverse event/side effects/complications 17 35.4
Alternative therapy 1 2.1
Death on study 6 12.5
Disease progression- relapse during active treatment 8 16.7
Other 2 4.2
Patient off-treatment for other complicating disease 3 6.3
Patient withdrawal/refusal after beginning protocol therapy 2 4.2
Treatment completed per protocol criteria 6 12.5
Total off treatment 45 93.8
ECOG-ACRIN Cancer Research Group E1411
Study Progress and Safety Report Spring 2016
Page 7
Table 5b. Reasons Off-Treatment – Step 2
(Includes all patients who started treatment and
for whom off-treatment data have been received)
Reasons N %
Adverse event/side effects/complications 8 13.6
Alternative therapy 1 1.7
Death on study 2 3.4
Disease progression- relapse during active treatment 17 28.8
Other 4 6.8
Patient withdrawal/refusal after beginning protocol therapy 3 5.1
Treatment completed per protocol criteria 19 32.2
Total off treatment 54 91.5
Table 6a. Treatment-Related Toxicities – Step 1
Toxicity Type
Treatment Arm
A (n=71) B (n=72) C (n=69) D (n=68)
Grade Grade Grade Grade
3 4 5 3 4 5 3 4 5 3 4 5
(n) (n) (n) (n) (n) (n) (n) (n) (n) (n) (n) (n)
Anemia 4 - - 1 - - - - - 4 1 -
Blood and lymphatic system disorders - Other, specify 1 - - - - - - - - - - -
Febrile neutropenia - - - 2 - - - 1 - 2 - -
Thrombotic thrombocytopenic purpura - - - - - - - - - 1 - -
Atrial fibrillation 1 - - - - - - - - 1 - -
Cardiac arrest - - - - - 1 - - - - - -
Left ventricular systolic dysfunction 1 - - 1 - - - - - - - -
Fatigue - - - 1 - - 1 - - - - -
Fever - - - - - - - - - 1 - -
Edema limbs 3 - - 1 - - - - - - - -
Infusion related reaction - - - 3 - - - - - 2 - -
Pruritus 1 - - - - - 1 - - 1 - -
Rash acneiform 1 - - - - - - - - - - -
Rash maculo-papular 2 - - 4 - - 2 - - 4 - -
Skin and subcutaneous tissue disorders - Other, specify 1 - - - - - 1 - - - - -
Abdominal distension 1 - - - - - - - - - - -
Abdominal pain - - - - - - - - - 1 - -
Colitis - - - 1 - - - - - - - -
Dental caries - - - 1 - - - - - - - -
Diarrhea 1 - - 2 - - - - - 1 - -
Mucositis oral - - - 1 - - - - - - - -
Nausea 2 - - 1 - - - - - - - -
Vomiting 2 - - 2 - - - - - - - -
Hepatobiliary disorders - Other, specify - - - - - 1 - - - - - -
Allergic reaction 1 - - 3 - - - - - 1 - -
Anaphylaxis - - - 1 - - - - - - - -
Immune system disorders - Other, specify - - - - - - - - - 1 - -
ECOG-ACRIN Cancer Research Group E1411
Study Progress and Safety Report Spring 2016
Page 8
Table 6a. Treatment-Related Toxicities – Step 1
Toxicity Type
Treatment Arm
A (n=71) B (n=72) C (n=69) D (n=68)
Grade Grade Grade Grade
3 4 5 3 4 5 3 4 5 3 4 5
(n) (n) (n) (n) (n) (n) (n) (n) (n) (n) (n) (n)
Cytokine release syndrome - - - 1 - - - - - - - -
Infections and infestations - Other, specify - - - 2 - - - - - 1 - -
Sepsis - 1 - - - - - 1 - - 2 -
Sinusitis 1 - - - - - - - - - - -
Skin infection - - - - - - - - - 1 - -
Upper respiratory infection - - - - - - - - - 1 - -
Lung infection 1 - - - - - 2 - - 1 - -
Alanine aminotransferase increased 1 - - - - - - - - - - -
Aspartate aminotransferase increased 1 - - - - - - - - - - -
CD4 lymphocytes decreased - - - 1 - - - - - - - -
Creatinine increased - - - - - - 1 - - - - -
INR increased - - - 1 - - - - - - - -
Lymphocyte count decreased 25 13 - 28 15 - 24 15 - 33 15 -
Lymphocyte count increased 1 - - - - - - - - - - -
Neutrophil count decreased 8 5 - 12 5 - 8 4 - 17 5 -
Platelet count decreased 5 - - 9 - - 5 - - 4 2 -
Weight gain 2 - - - - - - - - - - -
Weight loss - - - - - - - - - 1 - -
White blood cell decreased 9 1 - 12 5 - 7 1 - 14 2 -
Dehydration - - - - - - 1 - - - - -
Hyperglycemia - - - 1 - - - - - 2 - -
Hyperuricemia - - - - - - - - - - 1 -
Hypoalbuminemia - - - - - - 1 - - - - -
Hypocalcemia - - - 1 - - - - - - - -
Hypokalemia 2 - - - - - - - - - - -
Hypomagnesemia - - - - - - - - - 1 - -
Hyponatremia 2 - - 1 - - 1 1 - 1 - -
Hypophosphatemia - - - 1 - - - - - - - -
Tumor lysis syndrome - - - - - - - 1 1 - - -
Back pain - - - 2 - - - - - - - -
Generalized muscle weakness - - - - - - 1 - - - - -
Dizziness - - - - - - - - - 1 - -
Peripheral sensory neuropathy - - - 3 - - - - - 2 - -
Vasovagal reaction - - - 1 - - - - - - - -
Cataract - - - - - - - - - 1 - -
Insomnia - - - 2 - - - - - - - -
Dyspnea - - - - 1 - - - - - - -
Hypoxia 1 - - - 1 - - - - 1 - -
Pulmonary edema - - - - 1 - - - - - - -
Respiratory failure - - - - 1 - - - - - - -
Chronic kidney disease 1 - - 1 - - - - - - - -
Acute kidney injury - - - - - - 1 - - - - -
Flushing - - - - - - 1 - - - - -
Hypertension 3 - - 6 - - 3 - - 2 - -
ECOG-ACRIN Cancer Research Group E1411
Study Progress and Safety Report Spring 2016
Page 9
Table 6a. Treatment-Related Toxicities – Step 1
Toxicity Type
Treatment Arm
A (n=71) B (n=72) C (n=69) D (n=68)
Grade Grade Grade Grade
3 4 5 3 4 5 3 4 5 3 4 5
(n) (n) (n) (n) (n) (n) (n) (n) (n) (n) (n) (n)
Hypotension 1 - - 2 - - 2 - - 2 - -
Thromboembolic event - - - 1 - - - - - - - -
Vascular disorders - Other, specify - - - - - - - - - 1 - -
WORST DEGREE 34 19 - 41 18 2 29 19 1 33 24 -
Table 6b. Treatment-Related Toxicities – Step 2
Toxicity Type
Treatment Arm
E (n=39) F (n=42) G (n=41) H (n=43)
Grade Grade Grade Grade
3 4 5 3 4 5 3 4 5 3 4 5
(n) (n) (n) (n) (n) (n) (n) (n) (n) (n) (n) (n)
Anemia - - - - - - - - - 1 - -
Febrile neutropenia - - - 2 1 - 2 - - 2 1 -
Myocardial infarction - - - - - - - - 1 - - -
Fatigue - - - - - - 1 - - 2 - -
Fever - - - - - - - - - - 1 -
Pain - - - - - - 1 - - - - -
Rash maculo-papular - - - - - - 2 - - - - -
Palmar-plantar erythrodysesthesia syndrome - - - - - - 1 - - - - -
Diarrhea - - - - - - - - - 3 - -
Nausea - - - - - - - - - 1 - -
Allergic reaction - - - - - - - - - 1 - -
Infections and infestations - Other, specify 1 - - 1 - - - - - - - -
Skin infection 1 - - - - - - - - - - -
Lung infection 1 - - - - - 1 - - 2 1 -
Alanine aminotransferase increased - - - - - - - - - 1 - -
CPK increased - - - - 1 - - - - - - -
Creatinine increased - - - 1 - - - - - - - -
INR increased - - - - - - - - - 1 - -
Lymphocyte count decreased 12 6 - 14 4 - 18 3 - 21 6 -
Neutrophil count decreased 4 1 - 1 4 - 4 12 - 11 8 -
Platelet count decreased - - - - 1 - 1 - - 1 - -
Weight loss - - - - - - - - - 2 - -
White blood cell decreased 5 - - 2 3 - 12 4 - 12 - -
Anorexia - - - - - - - - - 1 - -
Dehydration - - - 1 - - - - - - - -
Hypokalemia - - - 1 - - 1 - - - - -
Hyponatremia - - - 1 - - - - - - - -
Generalized muscle weakness - - - 1 - - - - - - - -
Paresthesia - - - - - - - - - 1 - -
ECOG-ACRIN Cancer Research Group E1411
Study Progress and Safety Report Spring 2016
Page 10
Table 6b. Treatment-Related Toxicities – Step 2
Toxicity Type
Treatment Arm
E (n=39) F (n=42) G (n=41) H (n=43)
Grade Grade Grade Grade
3 4 5 3 4 5 3 4 5 3 4 5
(n) (n) (n) (n) (n) (n) (n) (n) (n) (n) (n) (n)
Peripheral sensory neuropathy - - - 1 - - - - - 1 - -
Syncope - - - - - - - - - 1 - -
Vasovagal reaction - - - - - - - - - 1 - -
Treatment related secondary malignancy - - - - - - 1 - - 1 - -
Cough - - - - - - - - - 2 - -
Dyspnea - - - - - - - - - 1 - -
Hypoxia - - - - - - 1 - - - - -
Pneumonitis - - - - - - 1 - - - - -
Chronic kidney disease - - - 1 - - - - - - - -
Hypertension - - - 2 - - 1 - - 1 - -
Hypotension - - - 1 - - - - - - - -
Thromboembolic event - - - - - - - - - 2 - -
WORST DEGREE 14 7 - 13 7 - 13 15 1 22 13 -
Table 6c. Treatment-Related Late Toxicities
Toxicity Type
Treatment Arm
OT (n=47)
Grade
3 4 5
(n) (n) (n)
Neutrophil count decreased - 1 -
White blood cell decreased 1 - -
WORST DEGREE - 1 -
Table 7. Lethal Adverse Events
Case Arm Description of Event
14208 B Hepatobiliary disorders
14247 C Tumor lysis syndrome
14279 B Cardiac arrest
14028 G Myocardial infarction
ECOG-ACRIN Cancer Research Group E1411
Study Progress and Safety Report Spring 2016
Page 11
Table 8. Second Primary Cancer
Cancer Site Treatment Arm
C D E G H
Basal cell carcinoma 1 - 1 - 3
Breast - - - - 1
Lung cancer - - - - 1
Melanoma - 1 - - 1
Skin cancer not melanoma 2 - - 2 -
Thyroid - - - - 1
Total 3 1 1 2 7
Table 9. Quality of Life Compliance
QOL Timepoint Patients Reaching Timepoint % Forms Completed
Baseline (Step 1) 302 99.67
6 Month QOL + End of Induction 210 88.57
12 Month QOL 101 81.19
Off Treatment Consolidation QOL
(due to reason other than progression) 43 69.77
Progression 26 65.38
51101 November 2016
Template Version Date: September 24, 2013
Alliance Study 51101 – A Randomized Phase II Trial Of Myeloablative Versus Non-Myeloablative Consolidation Chemotherapy For Newly Diagnosed Primary CNS B-Cell Lymphoma
Committee: Lymphoma Study Statisticians: Sin-Ho Jung, PhD Study Chair: Tracy Batchelor, MD, MPH Brandelyn N. Pitcher, MS 1.0 OBJECTIVES Primary
To compare the two-year progression-free survival (PFS) of patients treated with the myeloablative consolidation treatment strategy of HDT/ASCT versus those treated with non-myeloablative consolidation chemotherapy with cytarabine and etoposide
Secondary 1. To compare the two-year event-free survival (EFS) of patients treated with
consolidation HDT/ASCT versus those treated with consolidation chemotherapy consisting of etoposide and cytarabine
2. To compare the overall survival (OS) of patients treated with the consolidation HDT/ASCT versus those treated with consolidation chemotherapy consisting of etoposide and cytarabine
3. To assess the toxicities associated with consolidation HDT/ASCT versus consolidation consisting of etoposide and cytarabine
4. To determine diffusion MRI metrics (ADCmini, ADC25%, and ADCmean) prior to induction chemotherapy, after one full induction chemotherapy cycle, and at the end of induction chemotherapy as a predictor of response and outcome (CALGB 581101)
5. To determine brain FDG-PET metrics (tumor SUV and tumor versus background SUV) prior to induction chemotherapy, after one full induction chemotherapy cycle, and at the end of induction chemotherapy as a predictor of response and outcome (CALGB 581101)
6. To determine whether low baseline ADC measurements are associated with shorter PFS and OS (CALGB 581101)
7. To determine whether reduction in tumor SUV by > 25% on brain FDG-PET/CT after one cycle of induction therapy is associated with improved PFS and OS (CALGB 581101)
8. To determine which IHC-based biomarkers are predictive of an adverse prognosis (CALGB 151113)
9. To determine which IHC-based biomarkers are predictive of a favorable prognosis (CALGB 151113) for BCL6 (B-cell CLL/lymphoma 6), and STAT 6 (signal transducer and activator of transcription 6, interleukin-4 induced)
10. To analyze tumor tissue for gene expression profiles, and to correlate these profiles with treatment outcomes (CALGB 151113)
11. To determine whether CSF proteome is a predictor of outcomes (prognostic marker) irrespective of treatment arm [43] (CALGB 151113) for (IL-10 (interleukin 10) and C3 (complement component 3)
12. To assess the neurocognitive function of patients treated with consolidation HDT/ASCT versus those treated with consolidation chemotherapy (etoposide and cytarabine) as measured by serial administration of the International PCNSL Collaborative Group (IPCG) neurocognitive battery and evaluate the long-term survivorship differences between the two arms (CALGB 71105)
13. To assess the quality of life of patients treated with consolidation HDT/ASCT versus those treated with consolidation etoposide and cytarabine as measured by the EORTC Quality of Life Questionnaire-Core 30/Brain Cancer Module-20 (EORTC-QLQ30/BCM20), and to evaluate the long-term survivorship differences between the two arms (CALGB 71105)
51101 November 2016
Template Version Date: September 24, 2013
2.0 CURRENT SCHEMA
. 3.0 ELIGIBILITY CRITERIA
• Diffuse large B-cell lymphoma confined to the CNS; diagnosis by brain biopsy or resection, CSF, or vitreous fluid.
• No evidence of NHL outside of CNS; no history of NHL • No isolated ocular or leptomeningeal lymphoma • No prior chemotherapy or radiation therapy for lymphoma • At least one measurable, contract-enhancing brain lesion (≥ 1 cm in length) • Age 18-75 years • Karnofsky performance scale ≥ 30 (≥ 50 for patients ages 60-70) • Non-pregnant and non-nursing • Negative HIV serology • Negative HBV and HCV serology • No history of organ transplantation or ongoing immunosuppressant therapy • ANC ≥ 1500/mcL • AST & ALT ≤ 2 x ULN • Total bilirubin ≤ 3 mg/dL • Platelets ≥ 100,000/mcL • CrCl ≥ mL/min
4.0 TREATMENT SCHEDULE
The treatment schedule is described in detail in the Study Schema (Section 2.0 of this report).
51101 November 2016
Template Version Date: September 24, 2013
5.0 STUDY DESIGN
5.1 Study Phase/Type of Design/Stratification Factors This is a randomized phase II study. Patients will be randomized to HDT/ASCT or chemotherapy.
The intent to treat (ITT) analysis using the log-rank test with a one-sided alpha=10% will have 90% power to compare two-year PFS of 50% and 70% between the two arms. The final analysis will be conducted when 60 events (progressions or deaths) are observed from the patients who proceed to either HDT/ASCT or chemotherapy (or about 95 events from all the eligible patients). All randomized patients will be included in the final data analysis based on intent-to-treat analysis. The experimental therapy will be accepted for further investigation if the one-sided p-value is smaller than 0.1. The critical value c at the final analysis will be obtained by solving 1-alpha=P(Z1 > c1, Z > c) with respect to c, where (Z1, Z) is a bivariate normal random vector with means 0, variances 1 and correlation coefficient r=(v1/v)1/2, and v1 and v are variance estimates of the log-rank test at the interim and final analyses, respectively. Through simulations, the two-stage design is found to have about 9.7% of type I error and 87% power.
5.2 Primary Endpoint
The primary endpoint of this trial is to compare the two-year progression-free survival (PFS) of patients treated with the myeloablative consolidation treatment strategy of HDT/ASCT versus those treated with non-myeloablative consolidation chemotherapy with cytarabine and etoposide.
5.3 Target Accrual
A total of 160 patients (80 per arm) will be randomized between the control and experimental arms with 50:50 allocation proportions. The randomization will be conducted at registration, i.e. before induction therapy. Assuming that 80% of randomized subjects will achieve a radiographic response (CR, CRU, or PR) or stability (SD) and 5% will withdraw or will be ineligible, approximately 120 patients will be eligible for proceeding to either HCT/ASCT or chemotherapy. We expect an accrual rate of 6 patients per month.
6.0 CURRENT ACCRUAL
Study Activation Date 06/15/2012 Target Accrual (n) 160 Current Accrual (n) 81 Accrual Rate – Since activation 1.59/month Accrual Rate – Past 12 months (if applicable) 2.25/month Projected closure date for a trial open for more than one year (based on accrual rate from past 12 months)
09/08/2019
51101 November 2016
Template Version Date: September 24, 2013
7.0 CURRENT STUDY STATUS
This study was activated on 06/15/2012. The accrual as of 9/07/2016 was 81. 8.0 PATIENT CHARACTERISTICS Table 8a. Demographics
A
(N=40) B
(N=41) Total
(N=81) Age N 40 41 81 Mean (SD) 58.3 (10.0) 58.9 (10.4) 58.6 (10.2) Median 61.0 59.0 61.0 Q1, Q3 52.5, 66.0 55.0, 68.0 54.0, 67.0 Range (34.0-74.0) (34.0-75.0) (34.0-75.0) Race White 38 (95.0%) 39 (95.1%) 77 (95.1%) Asian 1 (2.5%) 1 (2.4%) 2 (2.5%) Not reported: patient refused or not available 0 (0.0%) 1 (2.4%) 1 (1.2%)
0 000 0 1 0
11 3 1 0 2 2 2 2 1 0 1 1 1 1 2
7 1 0 2 2 1 24 1 0 3 1 2 1 2 3 1 2 3 1 0 1
5 04 2 2
5 1 0
Expected Accrual 160 Patients
51101 November 2016
Template Version Date: September 24, 2013
A
(N=40) B
(N=41) Total
(N=81) Unknown: Patient unsure 1 (2.5%) 0 (0.0%) 1 (1.2%) Gender f 17 (42.5%) 17 (41.5%) 34 (42.0%) m 23 (57.5%) 24 (58.5%) 47 (58.0%)
Table 8b. Stratification Factors
A
(N=40) B
(N=41) Total
(N=81) Stratification#Factor Age < 51 years 8 (20.0%) 8 (19.5%) 16 (19.8%) Age >= 51 years and KPS >= 70 23 (57.5%) 24 (58.5%) 47 (58.0%) Age >= 51 years and KPS < 70 9 (22.5%) 9 (22.0%) 18 (22.2%)
9.0 ADVERSE EVENTS
9.1 Adverse Event Summary 66 (81.5%) patients are evaluable for adverse event (AE) analysis. Overall, 12 (18.2%) experienced a maximum grade 3 adverse event, 41 (62%) experienced a maximum grade 4 adverse event and 2 patient2 (3%) experienced a grade 5. The most commonly occurring grade 3/4 AEs include: neutrophil count decreased (60% Arm A, 59% Arm B), platelet count decreased (60% Arm A, 59% Arm B), lymphocyte count decreased (47% Arm A, 33% Arm B), anemia (50% Arm A, 38% Arm B), aspartate aminotransferase increased (30% Arm A; 27% Arm B) alanine aminotransferase increased (40% Arm A; 33% Arm B) and febrile neutropenia (43% Arm A, 15% Arm B), and hyperglycemia (17% Arm A; 29% Arm B).
Table 9a. Summary of Grade 3+ Adverse Events
Regardless of Attribution Number of Evaluable Patients:
Arm A=32 Arm B=34
Patients with a maximum: Arm n (%)
Total
Grade 3 Event A 7 (21.9%)
B 5 (14.7%)
Grade 4 Event A 20 (62.5%)
B 21 (61.8%)
Grade 5 Event A 1 (3.1%)
B 1 (2.9%)
Hematologic Adverse Events
Grade 3 Event A 5 (15.6%)
51101 November 2016
Template Version Date: September 24, 2013
Summary of Grade 3+ Adverse Events Regardless of Attribution
Number of Evaluable Patients: Arm A=32 Arm B=34
Patients with a maximum: Arm n (%)
B 4 (11.8%)
Grade 4 Event A 20 (62.5%)
B 20 (58.8%)
Grade 5 Event A 0 (0.0%)
B 0 (0.0%)
Non-Hematologic Adverse Events
Grade 3 Event A 21 (65.6%)
B 14 (41.2%)
Grade 4 Event A 4 (12.5%)
B 9 (26.5%)
Grade 5 Event A 1 (3.1%)
B 1 (2.9%)
Note: Summaries are based on available patient data Table 9b.
Listing of Grade 3+ Adverse Events Max Grade Per Patient Per Event
Regardless of Attribution Number of Evaluable Patients:
Arm A=32 Arm B=34 Grade of AdverseEvent
Arm 3-Severe 4-LifeThr 5-Lethal n (%) n (%) n (%)
Hematologic Adverse Events Blood/Bone Marrow
Anemia A 15 ( 50%) 0 ( 0%) 0 ( 0%) B 13 ( 38%) 0 ( 0%) 0 ( 0%) Blood and lymphat sys disord - Oth spec
A 1 ( 3%) 1 ( 3%) 0 ( 0%)
B 0 ( 0%) 1 ( 3%) 0 ( 0%) Leukocytosis A 2 ( 7%) 0 ( 0%) 0 ( 0%) B 1 ( 3%) 0 ( 0%) 0 ( 0%) Lymphocyte count decreased A 6 ( 20%) 8 ( 27%) 0 ( 0%) B 6 ( 18%) 5 ( 15%) 0 ( 0%) Lymphocyte count increased A 1 ( 3%) 0 ( 0%) 0 ( 0%) B 0 ( 0%) 0 ( 0%) 0 ( 0%) Neutrophil count decreased A 1 ( 3%) 17 ( 57%) 0 ( 0%)
51101 November 2016
Template Version Date: September 24, 2013
Listing of Grade 3+ Adverse Events Max Grade Per Patient Per Event
Regardless of Attribution Number of Evaluable Patients:
Arm A=32 Arm B=34 Grade of AdverseEvent
Arm 3-Severe 4-LifeThr 5-Lethal n (%) n (%) n (%)
B 2 ( 6%) 18 ( 53%) 0 ( 0%) Platelet count decreased A 5 ( 17%) 13 ( 43%) 0 ( 0%) B 0 ( 0%) 17 ( 50%) 0 ( 0%) White blood cell decreased A 2 ( 7%) 7 ( 23%) 0 ( 0%) B 3 ( 9%) 5 ( 15%) 0 ( 0%)
Non-Hematologic Adverse Events Blood and lymphatic sys disord
Febrile neutropenia A 12 ( 40%) 1 ( 3%) 0 ( 0%) B 5 ( 15%) 0 ( 0%) 0 ( 0%)
Cardiac disorders Supraventricular tachycardia A 0 ( 0%) 0 ( 0%) 0 ( 0%) B 0 ( 0%) 1 ( 3%) 0 ( 0%)
Ear and labyrinth disorders Hearing impaired A 1 ( 3%) 0 ( 0%) 0 ( 0%) B 0 ( 0%) 1 ( 3%) 0 ( 0%)
Gastrointestinal disorders Abdominal pain A 1 ( 3%) 0 ( 0%) 0 ( 0%) B 0 ( 0%) 0 ( 0%) 0 ( 0%) Colitis A 1 ( 3%) 0 ( 0%) 0 ( 0%) B 0 ( 0%) 0 ( 0%) 0 ( 0%) Dental caries A 1 ( 3%) 0 ( 0%) 0 ( 0%) B 1 ( 3%) 0 ( 0%) 0 ( 0%) Diarrhea A 1 ( 3%) 0 ( 0%) 0 ( 0%) B 1 ( 3%) 0 ( 0%) 0 ( 0%) Dysphagia A 1 ( 3%) 0 ( 0%) 0 ( 0%) B 0 ( 0%) 0 ( 0%) 0 ( 0%) Mucositis oral A 7 ( 23%) 0 ( 0%) 0 ( 0%) B 5 ( 15%) 0 ( 0%) 0 ( 0%) Nausea A 3 ( 10%) 0 ( 0%) 0 ( 0%) B 0 ( 0%) 0 ( 0%) 0 ( 0%) Pancreatic duct stenosis A 0 ( 0%) 0 ( 0%) 0 ( 0%) B 1 ( 3%) 0 ( 0%) 0 ( 0%) Rectal hemorrhage A 1 ( 3%) 0 ( 0%) 0 ( 0%) B 0 ( 0%) 0 ( 0%) 0 ( 0%) Vomiting A 1 ( 3%) 0 ( 0%) 0 ( 0%)
51101 November 2016
Template Version Date: September 24, 2013
Listing of Grade 3+ Adverse Events Max Grade Per Patient Per Event
Regardless of Attribution Number of Evaluable Patients:
Arm A=32 Arm B=34 Grade of AdverseEvent
Arm 3-Severe 4-LifeThr 5-Lethal n (%) n (%) n (%)
B 0 ( 0%) 1 ( 3%) 0 ( 0%) Gen disord and admin site cond
Fatigue A 3 ( 10%) 0 ( 0%) 0 ( 0%) B 0 ( 0%) 0 ( 0%) 0 ( 0%) Gait disturbance A 1 ( 3%) 0 ( 0%) 0 ( 0%) B 3 ( 9%) 0 ( 0%) 0 ( 0%) Sudden death NOS A 0 ( 0%) 0 ( 0%) 1 ( 3%) B 0 ( 0%) 0 ( 0%) 0 ( 0%)
Infections and infestations Abdominal infection A 0 ( 0%) 0 ( 0%) 0 ( 0%) B 1 ( 3%) 0 ( 0%) 0 ( 0%) Catheter related infection A 1 ( 3%) 0 ( 0%) 0 ( 0%) B 1 ( 3%) 0 ( 0%) 0 ( 0%) Encephalitis infection A 0 ( 0%) 0 ( 0%) 0 ( 0%) B 1 ( 3%) 0 ( 0%) 0 ( 0%) Enterocolitis infectious A 1 ( 3%) 0 ( 0%) 0 ( 0%) B 1 ( 3%) 0 ( 0%) 0 ( 0%) Infections and infestations - Oth spec
A 2 ( 7%) 1 ( 3%) 0 ( 0%)
B 1 ( 3%) 0 ( 0%) 0 ( 0%) Lung infection A 1 ( 3%) 0 ( 0%) 0 ( 0%) B 3 ( 9%) 0 ( 0%) 0 ( 0%) Mucosal infection A 1 ( 3%) 0 ( 0%) 0 ( 0%) B 0 ( 0%) 0 ( 0%) 0 ( 0%) Sepsis A 0 ( 0%) 1 ( 3%) 0 ( 0%) B 0 ( 0%) 0 ( 0%) 1 ( 3%) Sinusitis A 0 ( 0%) 0 ( 0%) 0 ( 0%) B 1 ( 3%) 0 ( 0%) 0 ( 0%) Urinary tract infection A 0 ( 0%) 0 ( 0%) 0 ( 0%) B 2 ( 6%) 0 ( 0%) 0 ( 0%) Wound infection A 1 ( 3%) 0 ( 0%) 0 ( 0%) B 0 ( 0%) 0 ( 0%) 0 ( 0%)
Investigations Actvtd prtl thromboplastin tm prolonged
A 0 ( 0%) 0 ( 0%) 0 ( 0%)
51101 November 2016
Template Version Date: September 24, 2013
Listing of Grade 3+ Adverse Events Max Grade Per Patient Per Event
Regardless of Attribution Number of Evaluable Patients:
Arm A=32 Arm B=34 Grade of AdverseEvent
Arm 3-Severe 4-LifeThr 5-Lethal n (%) n (%) n (%)
B 1 ( 3%) 0 ( 0%) 0 ( 0%) Alanine aminotransferase increased
A 12 ( 40%) 0 ( 0%) 0 ( 0%)
B 8 ( 24%) 3 ( 9%) 0 ( 0%) Aspartate aminotransferase increased
A 9 ( 30%) 0 ( 0%) 0 ( 0%)
B 7 ( 21%) 2 ( 6%) 0 ( 0%) Blood bilirubin increased A 1 ( 3%) 0 ( 0%) 0 ( 0%) B 0 ( 0%) 0 ( 0%) 0 ( 0%) Creatinine increased A 2 ( 7%) 0 ( 0%) 0 ( 0%) B 3 ( 9%) 0 ( 0%) 0 ( 0%) Investigations - Other, specify A 1 ( 3%) 0 ( 0%) 0 ( 0%) B 0 ( 0%) 0 ( 0%) 0 ( 0%) Urine output decreased A 0 ( 0%) 0 ( 0%) 0 ( 0%) B 1 ( 3%) 0 ( 0%) 0 ( 0%) Weight loss A 1 ( 3%) 0 ( 0%) 0 ( 0%) B 0 ( 0%) 0 ( 0%) 0 ( 0%)
Metabol and nutrition disord Alkalosis A 1 ( 3%) 0 ( 0%) 0 ( 0%) B 0 ( 0%) 0 ( 0%) 0 ( 0%) Anorexia A 3 ( 10%) 0 ( 0%) 0 ( 0%) B 0 ( 0%) 0 ( 0%) 0 ( 0%) Dehydration A 1 ( 3%) 0 ( 0%) 0 ( 0%) B 0 ( 0%) 0 ( 0%) 0 ( 0%) Glucose intolerance A 0 ( 0%) 0 ( 0%) 0 ( 0%) B 2 ( 6%) 0 ( 0%) 0 ( 0%) Hyperglycemia A 5 ( 17%) 0 ( 0%) 0 ( 0%) B 10 ( 29%) 0 ( 0%) 0 ( 0%) Hyperkalemia A 1 ( 3%) 0 ( 0%) 0 ( 0%) B 0 ( 0%) 0 ( 0%) 0 ( 0%) Hyperuricemia A 0 ( 0%) 1 ( 3%) 0 ( 0%) B 0 ( 0%) 0 ( 0%) 0 ( 0%) Hypoalbuminemia A 0 ( 0%) 0 ( 0%) 0 ( 0%) B 1 ( 3%) 0 ( 0%) 0 ( 0%) Hypocalcemia A 0 ( 0%) 0 ( 0%) 0 ( 0%)
51101 November 2016
Template Version Date: September 24, 2013
Listing of Grade 3+ Adverse Events Max Grade Per Patient Per Event
Regardless of Attribution Number of Evaluable Patients:
Arm A=32 Arm B=34 Grade of AdverseEvent
Arm 3-Severe 4-LifeThr 5-Lethal n (%) n (%) n (%)
B 1 ( 3%) 0 ( 0%) 0 ( 0%) Hypoglycemia A 1 ( 3%) 0 ( 0%) 0 ( 0%) B 0 ( 0%) 0 ( 0%) 0 ( 0%) Hypokalemia A 4 ( 13%) 1 ( 3%) 0 ( 0%) B 5 ( 15%) 0 ( 0%) 0 ( 0%) Hyponatremia A 0 ( 0%) 0 ( 0%) 0 ( 0%) B 3 ( 9%) 2 ( 6%) 0 ( 0%) Hypophosphatemia A 6 ( 20%) 0 ( 0%) 0 ( 0%) B 2 ( 6%) 0 ( 0%) 0 ( 0%)
Musculosk and conn tiss disord Arthritis A 1 ( 3%) 0 ( 0%) 0 ( 0%) B 0 ( 0%) 0 ( 0%) 0 ( 0%) Avascular necrosis A 1 ( 3%) 0 ( 0%) 0 ( 0%) B 0 ( 0%) 0 ( 0%) 0 ( 0%) Generalized muscle weakness A 4 ( 13%) 0 ( 0%) 0 ( 0%) B 0 ( 0%) 0 ( 0%) 0 ( 0%)
Nervous system disorders Ataxia A 0 ( 0%) 0 ( 0%) 0 ( 0%) B 1 ( 3%) 0 ( 0%) 0 ( 0%) Cognitive disturbance A 1 ( 3%) 0 ( 0%) 0 ( 0%) B 0 ( 0%) 0 ( 0%) 0 ( 0%) Edema cerebral A 0 ( 0%) 0 ( 0%) 0 ( 0%) B 0 ( 0%) 1 ( 3%) 0 ( 0%) Encephalopathy A 0 ( 0%) 0 ( 0%) 0 ( 0%) B 1 ( 3%) 0 ( 0%) 0 ( 0%) Headache A 1 ( 3%) 0 ( 0%) 0 ( 0%) B 0 ( 0%) 0 ( 0%) 0 ( 0%) Seizure A 1 ( 3%) 0 ( 0%) 0 ( 0%) B 0 ( 0%) 1 ( 3%) 0 ( 0%) Somnolence A 0 ( 0%) 0 ( 0%) 0 ( 0%) B 1 ( 3%) 0 ( 0%) 0 ( 0%) Syncope A 2 ( 7%) 0 ( 0%) 0 ( 0%) B 0 ( 0%) 0 ( 0%) 0 ( 0%)
Psychiatric disorders Confusion A 1 ( 3%) 0 ( 0%) 0 ( 0%)
51101 November 2016
Template Version Date: September 24, 2013
Listing of Grade 3+ Adverse Events Max Grade Per Patient Per Event
Regardless of Attribution Number of Evaluable Patients:
Arm A=32 Arm B=34 Grade of AdverseEvent
Arm 3-Severe 4-LifeThr 5-Lethal n (%) n (%) n (%)
B 3 ( 9%) 0 ( 0%) 0 ( 0%) Delirium A 0 ( 0%) 1 ( 3%) 0 ( 0%) B 0 ( 0%) 0 ( 0%) 0 ( 0%) Depression A 1 ( 3%) 0 ( 0%) 0 ( 0%) B 0 ( 0%) 0 ( 0%) 0 ( 0%) Insomnia A 0 ( 0%) 0 ( 0%) 0 ( 0%) B 1 ( 3%) 0 ( 0%) 0 ( 0%)
Renal and urinary disorders Acute kidney injury A 2 ( 7%) 0 ( 0%) 0 ( 0%) B 3 ( 9%) 0 ( 0%) 0 ( 0%)
Reprod sys and breast disord Menorrhagia A 1 ( 3%) 0 ( 0%) 0 ( 0%) B 0 ( 0%) 0 ( 0%) 0 ( 0%)
Respirat, thor, mediast disord Dyspnea A 1 ( 3%) 0 ( 0%) 0 ( 0%) B 0 ( 0%) 0 ( 0%) 0 ( 0%) Hypoxia A 0 ( 0%) 0 ( 0%) 0 ( 0%) B 0 ( 0%) 1 ( 3%) 0 ( 0%) Respiratory failure A 0 ( 0%) 1 ( 3%) 0 ( 0%) B 0 ( 0%) 0 ( 0%) 0 ( 0%)
Surgical and medical proced Surgical and medical proced - Oth spec
A 1 ( 3%) 0 ( 0%) 0 ( 0%)
B 0 ( 0%) 0 ( 0%) 0 ( 0%) Vascular disorders
Hematoma A 0 ( 0%) 0 ( 0%) 0 ( 0%) B 1 ( 3%) 0 ( 0%) 0 ( 0%) Hypertension A 3 ( 10%) 0 ( 0%) 0 ( 0%) B 6 ( 18%) 0 ( 0%) 0 ( 0%) Hypotension A 0 ( 0%) 0 ( 0%) 0 ( 0%) B 0 ( 0%) 1 ( 3%) 0 ( 0%) Thromboembolic event A 1 ( 3%) 0 ( 0%) 0 ( 0%) B 1 ( 3%) 1 ( 3%) 0 ( 0%)
10.0 IMBEDDED CORRELATIVES
51101 November 2016
Template Version Date: September 24, 2013
CALGB 151113, Exploratory Analyses of Biomarkers as Potential Predictors of Outcome for Primary CNS B-cell Lymphoma Participation to imbedded correlative 151113 was optional for all patient registered to 51101. As of September 8, 2016, there are 472 patients who consented. Samples are being collected and banked for future analysis. CALGB 581101, Imaging Markers of Outcome After Chemotherapy in Patients with Newly Diagnosed Primary CNS B-cell Lymphoma Participation to imbedded correlative 581101 was optional for all patient registered to 51101 at limited institutions. As of September 8, 2016, there are 11 patients who consented. Images are being collected and banked for future analysis. CALGB 71105, Neurocognitive Function and Quality of Life in Patients with Primary CNS B-cell Lymphoma Participation to imbedded correlative 71005 was optional for all patient registered to 51101. As of September 8, 2016, there are 56 patients who consented. QOL assessments are being collected and will be analyzed future analyses.