An Exploratory Phase 1/2 Trial To Evaluate The Safety And Efficacy Of JCAR017 Combinations In Subjects With Relapsed/Refractory B-Cell Malignancies (PLATFORM)
Phase: PHASE1
Conditions: Lymphoma, Non-Hodgkin, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Follicular
Sponsor: Celgene

 
 
Official Title of Study: 
An Exploratory Phase 1/2 Trial to Evaluate the Safety and Efficacy of JCAR017 Combinations in 
Subjects with Relapsed/Refractory B-Cell Malignancies (Platform) 
 
Protocol: JCAR017-BCM-002 
 
NCT Number: NCT03310619 
 
Document Date (Date in which document was last revised): 27-Jan-2021 

EDMS Doc. Number: 25256661 - 21712569
JCAR017
Protocol JCAR017-BCM-002
Celgene Corporation
Confidential and Proprietary
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Protocol JCAR017-BCM-002 Amendment 6 Final: 27 Jan 2021
 
AN EXPLORATORY PHASE 1/2 TRIAL TO EVALUATE 
THE SAFETY AND EFFICACY OF JCAR017 
COMBINATIONS IN SUBJECTS WITH 
RELAPSED/REFRACTORY B-CELL MALIGNANCIES 
(PLATFORM)
PROTOCOL NUMBER:
JCAR017-BCM-002
DATE FINAL:
03 Jun 2017
DATE AMENDMENT 6 FINAL:
27 Jan 2021
EudraCT NUMBER:
Not assigned yet
IND NUMBER:
017501
SPONSOR NAME/ ADDRESS:
Celgene Corporation
86 Morris Avenue
Summit, NJ 07901
CONFIDENTIAL
This protocol is provided to you as an Investigator, potential Investigator, or 
consultant for review by you, your staff, and ethics committee/institutional 
review board. The information contained in this document is regarded as 
confidential and, except to the extent necessary to obtain informed consent, 
may not be disclosed to another party unless such disclosure is required by 
law or regulations. Persons to whom the information is disclosed must be 
informed that the information is confidential and may not be further 
disclosed by them.
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MEDICAL MONITOR / EMERGENCY CONTACT INFORMATION 
Contact Information 
Name:
Title:
Address: 
  
Phone: (Office) 
(Mobile) 
email: 
Medical Monitor email: 
When contacting the Medical Monitor by email please always copy the study Medical Monitor 
Mailbox.
Note: The back-up 24-hour global emergency contact call center at Celgene should only be used 
if you are not able to reach the Clinical Research Physician(s) or Medical Monitor or designee 
for emergency calls. 
Back-up 24-hour Global Emergency Contact Call Center: 
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CELGENE THERAPEUTIC AREA HEAD SIGNATURE PAGE
(See appended electronic signature page)
Signature of Celgene Therapeutic Area Head
dd mmm yyyy
Printed Name of Celgene Therapeutic Area Head and Title
By my signature, I indicate I have reviewed this protocol and find its content to be 
acceptable.
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Protocol JCAR017-BCM-002
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SITE PRINCIPAL INVESTIGATOR SIGNATURE PAGE
Signature of Site Principal Investigator
dd mmm yyyy
Printed Name of Site Principal Investigator
Institution Name:_______________________________________
By my signature, I agree to personally supervise the conduct of this study at my study 
site and to ensure its conduct is in compliance with the protocol, informed consent, 
Institutional Review Board (IRB)/Ethics Committee (EC) procedures, instructions from 
Celgene representatives, the Declaration of Helsinki, International Council for 
Harmonisation (ICH), Good Clinical Practices Guidelines, and local regulations 
governing the conduct of clinical studies.
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Protocol JCAR017-BCM-002
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Protocol JCAR017-BCM-002 Amendment 6 Final: 27 Jan 2021
PROTOCOL SUMMARY
Study Title
An exploratory Phase 1/2 trial to evaluate the safety and efficacy of JCAR017 combinations in 
subjects with relapsed/refractory B-cell malignancies (PLATFORM) 
Indication
Relapsed/refractory (R/R) aggressive B-cell non-Hodgkin lymphoma (NHL) in subjects ≥ 18 
years.
Objectives
Primary Objective:
Dose finding (Phase 1):
To evaluate the safety and to define the recommended Phase 2 dose and schedule (RP2D) of 
JCAR017 combinations in adult subjects with R/R aggressive B-cell NHL
Dose expansion (Phase 2):
To evaluate the efficacy of JCAR017 combinations in adult subjects with R/R aggressive B-cell 
NHL defined as complete response rate (CRR)
Secondary Objectives:
Dose finding (Phase 1):

To assess the efficacy of JCAR017 combinations 
Dose expansion (Phase 2):

To assess the safety and other efficacy parameters of JCAR017 combinations

To characterize changes in health-related quality of life (HRQoL) outcome measures 
for subjects treated with JCAR017 combinations
Phase 1/2:

To characterize the pharmacokinetic (PK) profiles of JCAR017

To characterize the PK profiles of the respective combination agents
Study Design
This is a global, open-label, multi-arm, parallel multi-cohort, multi-center, Phase 1/2 study to 
determine the safety, tolerability, PK, efficacy and HRQoL of JCAR017 in combination with 
various agents. This protocol is intended to evaluate various drug combinations with JCAR017, 
as separate arms, over the life of the protocol, using the same objectives. Each combination will 
be evaluated separately (ie, the intention is not to compare between combinations) for the 
purposes of the objectives, trial design, and statistical analysis. The following combinations will 
be tested:

Arm A: JCAR017 in combination with durvalumab

Arm B: JCAR017 in combination with avadomide (CC-122)
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
Arm C: JCAR017 in combination with CC-220 (iberdomide)

Arm D: JCAR017 in combination with ibrutinib

Arm E: JCAR017 in combination with relatlimab and/or nivolumab

Arm F: JCAR017 in combination with CC-99282
Additional arms will be added by way of amendment once combination agents have been 
selected.
The study will consist of 2 parts: dose finding (Phase 1) and dose expansion (Phase 2). Dose 
expansion may occur in one or more arms.
During the Phase 1 part, different arms may be opened to test JCAR017 in combination with 
combination agent(s). Within each arm, different doses and schedules of JCAR017 and the 
combination agent(s) may be tested in several cohorts (referring to the setting of the 
combination, eg, post-expansion, post-infusion, or pre-infusion) and subcohorts (referring to the 
specific dose schedule) per arm. During the Phase 2 part of the study, the expansion of any dose 
level and schedule (or subcohort) for any arm that has been shown to be safe may occur.

Arm A will test JCAR017 in combination with durvalumab in adult subjects with 
R/R aggressive B-cell NHL. JCAR017 will be administered at a dose of 50 x 106
CAR+T cells (dose level 1 [DL1]) and 100 x 106 CAR+T cells (DL2) based on 
preliminary results from Study 017001 (NCT02631044). The combination agent will 
be administered at different doses and/ or schedules. 

Arm B will test JCAR017 in combination with CC-122 in adult subjects with R/R 
aggressive B-cell NHL. JCAR017 will be administered at a dose of 100 x 106
CAR+T cells (DL2) based on results from Study 017001. The combination agent will 
be administered at different doses. 

Arm C will test JCAR017 in combination with CC-220 (iberdomide) in adult 
subjects with R/R aggressive B-cell NHL. JCAR017 will be administered at a dose of 
100 x 106 CAR+T cells (DL2) based on results from Study 017001. The combination 
agent will be administered at different doses and/or schedules.

Arm D will test JCAR017 in combination with ibrutinib in adult subjects with R/R 
aggressive B-cell NHL. JCAR017 will be administered at a dose of 100 x 106
CAR+T cells (DL2) based on results from Study 017001. The combination agent may 
be administered at different doses and/or schedules.

Arm E will test JCAR017 in combination with relatlimab and/or nivolumab in adult 
subjects with R/R aggressive B-cell NHL. JCAR017 will be administered at a dose of 
100 x 106 CAR+T cells (DL2) based on results from Study 017001. The combination 
agent may be administered at different doses and/or schedules.

Arm F will test JCAR017 in combination with CC-99282 in adult subjects with R/R 
aggressive B-cell NHL. JCAR017 will be administered at a dose of 100 x 106
CAR+T cells (DL2) based on results from Study 017001. The combination agent may 
be administered at different doses and/or schedules.
Other combination arms may be opened at a later stage. Please refer to Section 3.1.
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During the dose and schedule finding part (Phase 1), a safety review committee (SRC) whose 
members include the medical monitor(s), drug safety physician, statistician, and a subset of 
investigators will recommend the Phase 2 dose and schedule (defined as RP2D) for each arm 
based on an integrated assessment of the safety, PK and pharmacodynamic (Pd) data, and 
preliminary efficacy information. The Bayesian Optimal Interval Design (BOIN) will be used for 
dose escalation/de-escalation decisions during the Phase 1 part of the study. The SRC may 
override the BOIN algorithm for safety concerns.
Enrollment will be staggered in Phase 1 in all arms, and a maximum of 9 dose-limiting toxicity 
(DLT) evaluable subjects will be evaluated in each subcohort. The first 6 subjects within a 
subcohort will enter the DLT period a minimum of 1 week apart or longer as specified for any 
individual Arm to allow appropriate safety monitoring. Dose-limiting toxicities will be assessed 
during the respective DLT period (see Section 9.3.1). 
A dose expansion cohort (Phase 2) may be opened at a dose level and schedule in any arm that 
has been shown to be safe with at least 6 DLT evaluable subjects through the DLT period. 
Enrollment will stop when approximately 35 subjects are evaluable for response at Month 3 at 
the dose and schedule chosen as an RP2D. All patients in Phase 2 will be followed for safety as 
outlined in Table 31. No more than one subject per week will be treated until 6 subjects have 
been treated with the combination agent, to allow appropriate safety monitoring. After 6 subjects 
have been treated at the RP2D in the expansion cohort, further enrollment rules will be 
determined by the Sponsor considering the recommendation of the SRC. 
All subjects from Phase 1 and Phase 2 will be followed for 24 months following JCAR017 
infusion for disease status, treatment related adverse events, and until last subject last visit for 
survival.
Long term safety and efficacy follow-up of subjects exposed to gene therapy medicinal products 
that utilize integrating vectors is required as per health authority regulatory guidelines to assess 
the risk of delayed adverse events, monitor for multicompetent retrovirus or lentivirus and to 
monitor for vector persistence. Therefore, all subjects who received JCAR017 infusion under this 
current protocol will be asked to roll-over upon either premature discontinuation from or 
completion of this study and participate in a separate long-term follow-up (LTFU) protocol for 
up to 15 years after their JCAR017 infusion. The study will be conducted in compliance with 
International Council for Harmonisation (ICH) and Good Clinical Practices (GCPs) and FDA 
Guidance for Industry (Food and Drug Administration, 2020).
Study Population
Adult subjects (≥ 18 years) with histologically confirmed aggressive B-cell NHL (defined as 
diffuse large B-cell lymphoma [DLBCL] not otherwise specified [NOS] including transformed 
indolent NHL; follicular lymphoma Grade 3B, T cell/histiocyte-rich large B-cell lymphoma, 
Epstein-Barr virus [EBV] positive DLBCL NOS, primary mediastinal [thymic] large B-cell 
lymphoma, or high grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements 
with DLBCL histology [double/triple-hit lymphoma (DHL/THL)] according to “The 2016 
revision of the World Health Organization [WHO] classification of lymphoid neoplasms”); who 
must have relapsed or be refractory to at least 2 prior lines of systemic therapy for the disease 
under study. Previous therapy must have included a CD20-targeted agent and an anthracycline.
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Length of Study
The enrollment rate is expected to be up to 4 subjects per month per arm for Phase 1 and up to 8 
subjects per month per arm for Phase 2. The length of the enrollment period depends on the final 
number of subjects enrolled in Phase 1 and the number of arms explored and further evaluated in 
Phase 2. For each study Arm and assuming a maximum of 77 subjects in total for Phase 1 and 
Phase 2, with up to 4 subcohorts the enrollment period is expected to take at least 9 months for 
Phase 1 and at least 7 months for Phase 2. The follow-up period for each subject is 
approximately 24 months after the infusion of JCAR017. Thus, the total duration for an arm of 
the study is expected to be approximately 60 months. 
The End of Trial is defined as either the date of the last visit of the last subject to complete the 
post-treatment follow-up, or the date when the last subject enters the LTFU study, or the date of 
receipt of the last data point from the last subject that is required for primary, secondary and/or 
exploratory analysis, as pre-specified in the protocol, whichever is the later date.
Study Treatments
Subjects will receive treatment with JCAR017 (lisocabtagene maraleucel; liso-cel) and 
combination agent(s) at different doses and schedules. Subjects will be assigned to an arm and a 
subcohort by the Sponsor based on the subject’s eligibility and slot availability. Subjects 
assigned to Arm A will receive JCAR017 in combination with durvalumab. Subjects assigned to 
Arm B will receive JCAR017 in combination with CC-122. Subjects assigned to Arm C will 
receive JCAR017 in combination with CC-220. Subjects assigned to Arm D will receive 
JCAR017 in combination with ibrutinib. Subjects assigned to Arm E will receive JCAR017 in 
combination with nivolumab with or without relatlimab. Subjects assigned to Arm F will receive 
JCAR017 in combination with CC-99282. Subjects who do not receive the combination 
treatment for any cause (eg, toxicity to the first therapy) will be replaced. 
Overview of Key Efficacy Assessments
Positron emission tomography (PET)- computed tomography (CT)/ magnetic resonance imaging 
(MRI) assessment of response will be performed at baseline and approximately 1, 3, 6, 9, 12, 18, 
and 24 months following the JCAR017 infusion. Response and response-based endpoints will be 
assessed through local review for Phase 1 and for Phase 2 using the Lugano Classification. 
Treatment decisions will be based on investigator assessed response, and scans will be collected 
centrally to allow for a potential central review.
Overview of Key Safety Assessments
Safety will be monitored by physical examination, laboratory evaluation, neurologic 
examination, as well as by collecting adverse events (AEs).
Phase 1: DLTs will be assessed during the respective DLT period.
The following events will be considered DLTs: 

Death not related to progression

Grade 4 neurotoxicity

Grade 3 neurotoxicity of greater than 7 days’ duration 
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
Grade 3 neurotoxicity that does not revert to baseline within 28 days of the start date 
of the Grade 3 event 

Grade 3 seizures that do not resolve to grade ≤ 2 within 3 days 

Grade 4 cytokine release syndrome (CRS)

Grade 3 CRS that does not resolve to Grade ≤ 2 within 7 days 

Febrile neutropenia (defined by temperature ≥ 38.3°C and ANC < 0.5 x 109 /L) that 
does not resolve within 72 hours

Any increase in aspartate aminotransferase (AST) or alanine aminotransferase (ALT) 
> 5 × upper-limit of normal (ULN) and concurrent increase in total bilirubin > 3 × 
ULN that is unrelated to CRS and has no other probable reason to explain the 
combination of increases 

Any cardiac, dermatologic, gastrointestinal, hepatic, pulmonary, renal/genitourinary, 
or neurologic Grade 3 or 4 event not pre-existing or not due to the underlying 
malignancy

Any Grade 3 or 4 event deemed unexpected by the Investigator and considered a DLT 
upon evaluation by the SRC

Any  dose modification of the combination agent required based on a related AE or 
treatment interruption greater than 2 weeks
For Arm A, the following additional combination treatment-related events will be considered 
DLTs (if occurring after start of durvalumab):

Grade ≥ 3 non-infectious colitis or non-infectious pneumonitis

Grade ≥ 3 immune-related adverse event (irAE) or other Grade ≥ 3 autoimmune 
toxicity (excluding B-cell aplasia) 
For Arm B, the following additional combination treatment-related events will be considered 
DLTs (if occurring after start of CC-122):

Grade 4 neutropenia lasting ≥ 7 days

Grade 3 or 4 thrombocytopenia with clinically significant bleeding

Grade 4 thrombocytopenia lasting > 24h
For Arm C, the following additional combination treatment-related events will be considered 
DLTs (if occurring after start of CC-220)

Grade 4 neutropenia lasting ≥ 7 days

Grade 3 or 4 thrombocytopenia with clinically significant bleeding
For Arm D, the following additional combination treatment-related events will be considered 
DLTs (if occurring after start of combination therapy): 

Grade 4 neutropenia lasting ≥ 7 days

Grade 3 or 4 thrombocytopenia with clinically significant bleeding
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For Arm E, the following additional combination treatment-related events will be considered 
DLTs (if occurring after start of combination therapy): 

Grade ≥ 3 non-infectious colitis or non-infectious pneumonitis 

Grade ≥ 3 immune-related adverse event (irAE) or other Grade ≥ 3 autoimmune 
toxicity (excluding B-cell aplasia) 

Grade 2 immune related-eye pain or reduction in visual acuity that requires systemic 
treatment

Grade 2 eye pain or reduction in visual acuity that does not respond to topical therapy 
and that does not improve to Grade 1 within 2 weeks of initiation of topical therapy

Grade 4 anemia

Grade 3 hemolysis

Grade 3 or 4 thrombocytopenia with clinically significant bleeding
For Arm F, the following additional combination treatment-related events will be considered 
DLTs (if occurring after start of combination therapy):

Grade 4 anemia

Grade 4 neutropenia lasting ≥ 7 days

Grade 3 or 4 thrombocytopenia with clinically significant bleeding
Statistical Methods
Phase 1:
Escalation or de-escalation will be based on the BOIN algorithm. With the target DLT rate of 
0.30, the BOIN escalation boundary is λe=0.236 and the de-escalation boundary is λd=0.358. 
The BOIN dosing decision table is provided in Table 9.
Enrollment into Phase 1 of the study will be staggered such that in each arm, the first 6 subjects 
within a subcohort will enter the DLT period at intervals of at least 1 week. No more than 6 
subjects can be in the DLT period simultaneously across subcohorts of a given arm that has not 
yet been shown to be safe. For a dose level to be shown to be safe, at least 6 DLT evaluable 
subjects must have completed the DLT period and it is estimated to be safe per the BOIN 
algorithm. Enrollment to the next dose level will be prioritized if open for enrollment. 
Within each arm, a sample size of at least 6 DLT evaluable subjects per subcohort is planned 
with no more than 9 DLT evaluable subjects treated in a subcohort. The final number of subjects 
needed in Phase 1 in a given arm will depend on the number of DLTs observed within each 
subcohort. Non-DLT evaluable subjects will be replaced. With an expected rate of non-DLT 
evaluable subjects of around 30%, up to about 24 subjects may be enrolled in Phase 1 into arms 
A, B and F, up to about 48 subjects may need to be enrolled in Phase 1 in Arms C and E, and up 
to 12 subjects in Phase 1 in Arm D.
Subjects must have elevated disease burden at screening (sum of product of perpendicular 
diameters (SPD) of index lesions ≥ 25 cm2 by CT scan). Arms A and B are not subject to this 
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TABLE OF CONTENTS
TITLE PAGE..............................................................................................................................1
PROTOCOL SUMMARY ..........................................................................................................5
1.
INTRODUCTION..................................................................................................27
1.1.
Disease Background ...............................................................................................27
1.1.1.
Non-Hodgkin Lymphoma.......................................................................................27
1.1.2.
CD19 as a Therapeutic Target.................................................................................28
1.1.3.
CD19–Targeted Chimeric Antigen Receptors .........................................................28
1.2.
Compound Background ..........................................................................................28
1.2.1.
JCAR017 Investigational Drug Product ..................................................................28
1.2.2.
Durvalumab (MEDI4736).......................................................................................29
1.2.3.
CC-122 (Avadomide) .............................................................................................29
1.2.4.
CC-220 (Iberdomide)..............................................................................................30
1.2.5.
Ibrutinib..................................................................................................................30
1.2.6.
Relatlimab ..............................................................................................................31
1.2.7.
Nivolumab..............................................................................................................31
1.2.8.
CC-99282...............................................................................................................31
1.3.
Rationale ................................................................................................................32
1.3.1.
Study Rationale and Purpose ..................................................................................32
1.3.2.
Rationale for the Study Design ...............................................................................33
1.3.3.
Rationale for Dose, Schedule and Regimen Selection .............................................34
1.3.3.1.
JCAR017 Dose Rationale .......................................................................................34
1.3.4.
Rationale for Choice of Combination Compounds ..................................................34
1.3.4.1.
Rationale for JCAR017 in Combination with PD-1 or PD-L1 Blockade..................34
1.3.4.2.
Rationale for JCAR017 in Combination With CC-122............................................36
1.3.4.3.
Rationale for JCAR017 in Combination With CC-220............................................37
1.3.4.4.
Rationale for JCAR017 in Combination With Ibrutinib...........................................38
1.3.4.5.
Rationale for JCAR017 in Combination with Relatlimab and Nivolumab ...............39
1.3.4.6.
Rationale for JCAR017 in Combination With CC-99282........................................40
...................42
1.3.5.1.
JCAR017 Pharmacokinetics, Immunogenicity, and Cytokine Secretion ..................42
1.3.5.2.
Circulating JCAR017 and Endogenous T Cell Phenotype .......................................43
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..................................................44
2.
STUDY OBJECTIVES AND ENDPOINTS...........................................................46
3.
OVERALL STUDY DESIGN ................................................................................51
3.1.
Study Design ..........................................................................................................51
3.1.1.
Phase 1 ...................................................................................................................51
3.1.2.
All Phases...............................................................................................................53
3.1.3.
Study Arm A (JCAR017 in Combination with Durvalumab)...................................53
3.1.3.1.
Durvalumab Dose Rationale ...................................................................................53
3.1.4.
Study Arm B (JCAR017 in Combination with CC-122)..........................................55
3.1.4.1.
CC-122 Dose Rationale ..........................................................................................56
3.1.5.
Study Arm C (JCAR017 in Combination With CC-220).........................................57
3.1.5.1.
CC-220 Dose Rationale ..........................................................................................57
3.1.6.
Study Arm D (JCAR017 in Combination With Ibrutinib)........................................59
3.1.6.1.
Ibrutinib - Dose Rationale.......................................................................................59
3.1.7.
Study Arm E (JCAR017 in Combination With Relatlimab and/or 
Nivolumab) ............................................................................................................61
3.1.7.1.
Nivolumab and Relatlimab Dose Rationale.............................................................61
3.1.7.2.
Relatlimab and Nivolumab Dose Schedule .............................................................63
3.1.8.
Study Arm F (JCAR017 in Combination With CC-99282)......................................65
3.1.8.1.
CC-99282 Dose Rationale ......................................................................................65
3.1.9.
Dose and Cohort Decision Rules.............................................................................67
3.1.9.1.
Arm A ....................................................................................................................67
3.1.9.2.
Arm B ....................................................................................................................67
3.1.9.3.
Arm C ....................................................................................................................68
3.1.9.4.
Arm D ....................................................................................................................68
3.1.9.5.
Arm E.....................................................................................................................68
3.1.9.6.
Arm F.....................................................................................................................70
3.1.9.7.
Dose Escalation and De-Escalation Rules ...............................................................70
3.2.
Stopping Rules .......................................................................................................71
3.2.1.
Criteria for Pausing or Stopping the Study..............................................................71
3.3.
Safety Monitoring Boundaries ................................................................................72
3.4.
Study Duration for Subjects....................................................................................73
3.5.
End of Trial ............................................................................................................73
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4.
STUDY POPULATION.........................................................................................74
4.1.
Number of Subjects ................................................................................................74
4.2.
Inclusion Criteria....................................................................................................74
4.3.
Exclusion Criteria...................................................................................................77
5.
TABLES OF EVENTS...........................................................................................80
5.1.
Arm A ....................................................................................................................80
5.2.
Arm B ....................................................................................................................93
5.3.
Arm C ..................................................................................................................100
5.3.1.
Arm C – For Subjects Continuing CC-220 Beyond Day 85...................................107
5.4.
Arm D ..................................................................................................................108
5.5.
Arm E...................................................................................................................115
5.6.
Arm F...................................................................................................................145
6.
PROCEDURES....................................................................................................153
6.1.
Pre-Treatment Period............................................................................................153
6.1.1.
Screening (Approximately 1 to 2 Weeks Prior to Leukapheresis)..........................153
6.1.2.
Leukapheresis (Approximately 4 Weeks Prior to JCAR017 Administration).........155
6.1.3.
Pre-Lymphodepletion Evaluation..........................................................................157
6.2.
Treatment Period ..................................................................................................158
6.2.1.
Lymphodepleting Chemotherapy..........................................................................158
6.2.2.
Day 1 (JCAR017 Administration).........................................................................159
6.2.3.
Days 2, 3, and 4 (+ 1 day for Day 4) .....................................................................161
6.2.4.
Days 8 and 11 (± 1 day)........................................................................................162
6.2.5.
Days 15 and 22 (± 2 days) ....................................................................................163
6.2.6.
Day 29 (± 7 days) .................................................................................................164
6.2.7.
Days 30, 31, 32 and 39 (Arm B) ...........................................................................166
6.2.8.
Days 36, 43, and 57 (± 2 days)..............................................................................167
6.2.9.
Days 50, 64, 71 and 78 (± 2 days) (Arm B)...........................................................169
6.2.10.
Day 85 (± 7 days) .................................................................................................169
6.2.11.
Day 113 (± 7 days) (Arm B) .................................................................................171
6.2.12.
Days 141 and 169 (± 7 days) (Arm B) ..................................................................171
6.2.13.
Day 180 (± 7 days) (Arm B) .................................................................................172
6.3.
Post-Treatment Period ..........................................................................................172
6.3.1.
Follow-up.............................................................................................................172
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6.3.1.1.
Specific Follow-up for Durvalumab After Day 85 in Arm A.................................174
6.3.1.2.
Specific Follow-up for CC-122 After Day 180 in Arm B ......................................175
6.3.1.3.
Specific Follow-up for CC-220 After Day 85 in Arm C ........................................175
6.3.2.
Unscheduled Evaluations......................................................................................176
6.3.3.
Assessments Upon Disease Progression................................................................177
6.3.3.1.
Assessments Upon Start of Subsequent Anticancer Treatment ..............................177
6.3.4.
Assessments at Time of Death ..............................................................................177
6.3.5.
Early Withdrawal..................................................................................................178
6.3.6.
New Malignancies Follow-up Period....................................................................178
6.3.7.
Survival Follow-up...............................................................................................178
6.3.8.
Long-Term Follow-up ..........................................................................................178
6.4.
Safety Assessments...............................................................................................178
6.4.1.
Physical Examination ...........................................................................................178
6.4.2.
Vital Signs............................................................................................................178
6.4.3.
Pulse Oximetry.....................................................................................................179
6.4.4.
Height and Weight................................................................................................179
6.4.5.
Routine Neurologic and Mini Mental State Examinations.....................................179
6.4.6.
Cerebrospinal Fluid Assessment ...........................................................................179
6.4.7.
ECOG Performance Status....................................................................................179
6.4.8.
Multi-gated Acquisition Scan / Echocardiogram...................................................179
6.4.9.
Electrocardiogram ................................................................................................179
............................................................180
.............................................................................180
6.4.12.
Clinical Laboratory Evaluations............................................................................180
6.5.
Efficacy Assessment.............................................................................................181
6.5.1.
Potential Pseudoprogression .................................................................................181
..................................................................................................181
.............................................................................181
.........................................................................181
................................................................................181
................................................................................182
...............................................................................182
...................................................182
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.............................................................................183
.....................................183
...............................................................................183
........................................................................................184
6.8.
Subject Reported Outcomes or Health-Related Quality of Life or Health 
Economics............................................................................................................185
6.8.1.
EORTC QLQ-C30................................................................................................186
6.8.2.
EQ-5D-5L ............................................................................................................186
..........................................................187
...............................................................................189
7.
DESCRIPTION OF STUDY TREATMENTS......................................................190
7.1.
Description of Investigational Product(s)..............................................................190
7.1.1.
JCAR017 (Lisocabtagene maraleucel; liso-cel).....................................................190
7.1.2.
Durvalumab (Arm A) ...........................................................................................190
7.1.3.
CC-122 (Arm B)...................................................................................................190
7.1.4.
CC-220 (Arm C)...................................................................................................190
7.1.5.
Ibrutinib (Arm D) .................................................................................................190
7.1.6.
Relatlimab (Arm E) ..............................................................................................190
7.1.7.
Nivolumab (Arm E)..............................................................................................190
7.1.8.
CC-99282 (Arm F) ...............................................................................................190
7.2.
Treatment Administration and Schedule ...............................................................190
7.2.1.
Lymphodepleting Chemotherapy..........................................................................190
7.2.2.
JCAR017 Treatment .............................................................................................191
7.2.2.1.
JCAR017 Dose and Schedule ...............................................................................191
7.2.2.2.
JCAR017 Preparation and Cell Thawing...............................................................191
7.2.2.3.
JCAR017 Premedication.......................................................................................191
7.2.2.4.
JCAR017 Administration......................................................................................192
......................................................................................192
...........................................................................192
...........................................................192
7.2.4.
Durvalumab Treatment.........................................................................................193
7.2.4.1.
Durvalumab Drug Product....................................................................................193
7.2.4.2.
Durvalumab Premedication...................................................................................193
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7.2.4.3.
Durvalumab Preparation and Administration ........................................................193
7.2.4.4.
Durvalumab Dose Interruptions............................................................................194
7.2.4.5.
Durvalumab Dose Modification Guidelines ..........................................................194
................................................................................................194
...........................................................................................194
.........................................................................................194
...................................................................................195
................................................................................................195
...........................................................................................195
.........................................................................................196
...................................................................................196
7.2.7.
Ibrutinib Treatment...............................................................................................196
7.2.7.1.
Ibrutinib Drug Product..........................................................................................196
7.2.7.2.
Ibrutinib Administration .......................................................................................197
7.2.7.3.
Ibrutinib Dose Modification..................................................................................197
..............................................................197
............................................................................................199
.......................................................................................199
.....................................................................................199
...............................................................................199
.....................................................................199
7.2.11.
Overdose ..............................................................................................................201
7.3.
Method of Treatment Assignment.........................................................................202
7.3.1.
Packaging and Labeling........................................................................................202
7.3.2.
Cell Product Supply and Storage...........................................................................202
7.4.
Investigational Product Accountability and Disposal ............................................202
7.4.1.
Accountability Procedures....................................................................................202
.............................................................................202
......................................................................202
8.
CONCOMITANT MEDICATIONS AND PROCEDURES..................................204
8.1.
Permitted Concomitant Medications and Procedures.............................................204
8.1.1.
Anticancer Treatments between Leukapheresis and Lymphodepleting 
Chemotherapy ......................................................................................................205
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8.1.2.
Growth Factors and Transfusions of Blood and Blood Products............................205
8.1.3.
Thromboembolic Event Prophylaxis.....................................................................206
8.2.
Prohibited Concomitant Medications and Procedures............................................206
8.2.1.
Additional Concomitant Medication Guidance for Arm B.....................................207
8.2.2.
Additional Concomitant Medication Guidance for Arm C.....................................208
8.2.3.
Additional Concomitant Medication Guidance for Arm D ....................................208
8.2.4.
Additional Concomitant Medication Guidance for Arm F.....................................208
8.3.
Required Concomitant Medications and Procedures..............................................209
9.
STATISTICAL CONSIDERATIONS ..................................................................210
9.1.
Overview..............................................................................................................210
9.2.
Study Population Definitions ................................................................................210
9.2.1.
Screened Set.........................................................................................................210
9.2.2.
Enrolled Set..........................................................................................................210
9.2.3.
Leukapheresed Set................................................................................................211
9.2.4.
JCAR017 Treated Set ...........................................................................................211
9.2.5.
Combination Treated Set ......................................................................................211
9.2.6.
Safety Set .............................................................................................................211
9.2.7.
DLT Evaluable Set ...............................................................................................211
9.2.8.
Efficacy Evaluable Set..........................................................................................211
.................................................................211
...............................................................................211
9.3.
DLT Related Definitions.......................................................................................211
9.3.1.
Definition of DLT Evaluation Period....................................................................211
9.3.1.1.
Arms A, B and C ..................................................................................................212
9.3.1.2.
Arm D ..................................................................................................................212
9.3.1.3.
Arm E...................................................................................................................212
9.3.1.4.
Arm F...................................................................................................................212
9.3.2.
Definition of a Subject Evaluable for DLTs ..........................................................212
9.4.
Sample Size and Power Considerations.................................................................212
9.4.1.
Phase 1 .................................................................................................................212
9.4.2.
Phase 2 .................................................................................................................213
9.4.3.
Total Sample Size.................................................................................................213
9.5.
Background and Demographic Characteristics......................................................213
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9.6.
Subject Disposition...............................................................................................213
9.6.1.
Phase 1 .................................................................................................................213
9.6.2.
Phase 2 .................................................................................................................214
9.7.
Efficacy Analysis..................................................................................................214
9.7.1.
Primary Efficacy Analysis (Phase 2).....................................................................214
9.7.2.
Secondary Efficacy Analysis (Phase 1 and Phase 2)..............................................215
...............................................................................................215
9.8.
Safety Analysis.....................................................................................................216
9.8.1.
Phase 1 DLT.........................................................................................................216
9.8.2.
Adverse Events.....................................................................................................216
9.9.
Laboratory Evaluations.........................................................................................218
9.9.1.
Numeric Laboratory Results .................................................................................218
9.9.2.
Graded Laboratory Values....................................................................................218
9.9.3.
Summaries of Laboratory Abnormalities...............................................................218
9.10.
Interim Analysis ...................................................................................................219
9.11.
Other Topics.........................................................................................................219
9.11.1.
Safety Review Committee ....................................................................................219
9.11.2.
Data Safety Monitoring Board..............................................................................219
..................................................................................................219
............................................................................................220
10.
ADVERSE EVENTS............................................................................................221
10.1.
Monitoring, Recording and Reporting of Adverse Events .....................................221
10.2.
Evaluation of Adverse Events...............................................................................223
10.2.1.
Seriousness...........................................................................................................223
10.2.2.
Severity/Intensity..................................................................................................224
10.2.3.
Causality ..............................................................................................................225
10.2.4.
Duration ...............................................................................................................225
10.2.5.
Action Taken........................................................................................................225
10.2.6.
Outcome...............................................................................................................225
10.3.
Abnormal Laboratory Values................................................................................226
10.4.
Pregnancy.............................................................................................................226
10.4.1.
Females of Childbearing Potential ........................................................................226
10.4.2.
Male Subjects.......................................................................................................227
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10.5.
Reporting of Serious Adverse Events....................................................................227
10.5.1.
Safety Queries ......................................................................................................227
10.5.2.
Death Reports.......................................................................................................227
10.6.
Potential Risks and Management of Treatment Toxicities.....................................228
10.6.1.
Management of Toxicities Associated with JCAR017...........................................228
10.6.1.1.
Cytokine Release Syndrome .................................................................................228
10.6.1.2.
Fever ....................................................................................................................229
10.6.1.3.
Cytopenias............................................................................................................229
10.6.1.4.
Infections..............................................................................................................229
10.6.1.5.
Neurologic Toxicities ...........................................................................................229
10.6.1.6.
Macrophage Activation Syndrome........................................................................229
10.6.1.7.
Infusion Reactions ................................................................................................230
10.6.1.8.
Tumor Lysis Syndrome ........................................................................................230
10.6.1.9.
B-cell Aplasia.......................................................................................................230
10.6.1.10. Graft-Versus-Host Disease ...................................................................................231
..........................................................................231
............231
10.6.2.
Risks Associated with Lymphodepleting Chemotherapy.......................................231
10.6.3.
Risks Associated with Durvalumab.......................................................................232
..............................................................................233
....................................................................233
..............................................................................................................233
...........................................................................................233
........................................................................................234
..........................................................................................................234
.......................................................................................234
....................................................................................................234
..............................................................................235
....................................................................235
.......................................................................................235
......................................................................................................235
..................................................................................................235
..............................................................................................................236
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........................................................................236
10.6.6.
Risks Associated with Ibrutinib ............................................................................236
10.6.6.1.
Hemorrhage..........................................................................................................236
10.6.6.2.
Infections..............................................................................................................236
10.6.6.3.
Cytopenias............................................................................................................236
10.6.6.4.
Cardiac Arrhythmias.............................................................................................236
10.6.6.5.
Hypertension ........................................................................................................237
10.6.6.6.
Tumor Lysis Syndrome ........................................................................................237
10.6.6.7.
Embryo-Fetal Toxicity..........................................................................................237
................................................237
........................................238
10.6.7.2.
Clinical Safety of Nivolumab Monotherapy..........................................................238
..........................................................238
.....................................239
10.6.7.5.
Complications of Allogeneic Hematopoietic Stem Cell Transplantation................242
.........................................................................242
....................................................................242
.......................................................................................242
...............................................................................................................243
..................................................................................................243
................................................................................................243
10.7.
Expedited Reporting of Adverse Events................................................................243
11.
DISCONTINUATIONS .......................................................................................245
11.1.
Treatment Discontinuation....................................................................................245
11.2.
Study Discontinuation ..........................................................................................245
12.
EMERGENCY PROCEDURES...........................................................................246
12.1.
Emergency Contact...............................................................................................246
12.2.
Emergency Identification of Investigational Products ...........................................246
13.
REGULATORY CONSIDERATIONS.................................................................247
13.1.
Good Clinical Practice..........................................................................................247
13.2.
Investigator Responsibilities .................................................................................247
13.3.
Subject Information and Informed Consent...........................................................248
13.4.
Confidentiality......................................................................................................248
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LIST OF TABLES
Table 1:
Study Objectives.....................................................................................................46
Table 2:
Study Endpoints .....................................................................................................48
Table 3:
Arm A Dosing Schedule .........................................................................................55
Table 4:
Arm B Dosing Schedule .........................................................................................57
Table 5:
Arm C Dosing Schedule .........................................................................................59
Table 6:
Arm D Dosing Schedule .........................................................................................61
Table 7:
Arm E Dosing Schedule..........................................................................................65
Table 8:
Arm F Dosing Schedule..........................................................................................67
Table 9:
Dose Escalation and De-Escalation Rules Based on BOIN Algorithm.....................71
Table 10:
Table of Events, Arm A Cohort 1 ...........................................................................80
Table 11:
Table of Events, Arm A Cohort 1A-2 .....................................................................87
Table 12:
Table of Events, Arm B Cohort 1............................................................................93
Table 13:
Table of Events, Arm C ........................................................................................100
Table 14:
Table of Events, Arm C Subjects Continuing CC-220 Beyond Day 85..................107
Table 15:
Table of Events, Arm D........................................................................................108
Table 16:
Table of Events, Arm E Cohorts 1A, 1B, 1C.........................................................115
Table 17:
Table of Events, Arm E Cohorts 1A+1, 1B+1, 1C+1 ............................................123
Table 18:
Table of Events, Arm E Cohorts 1A-1, 1B-1, 1C-1...............................................131
Table 19:
Table of Events, Arm E Cohorts 1A+2, 1B+2, 1C+2 ............................................138
Table 20:
Table of Events, Arm F.........................................................................................145
Table 21:
Links to Tables of Events .....................................................................................153
Table 22:
Washout Periods Prior to Leukapheresis...............................................................156
...................................................................182
...................................................................183
................................................................185
...............................188
........................................................................195
........................................................................196
Table 29:
Ibrutinib Dose Modification Levels ......................................................................197
Table 30:
Reporting Periods for Concomitant Medications...................................................204
Table 31:
Recording Periods for Adverse Events..................................................................222
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LIST OF FIGURES
Figure 1:
High Level Study Design........................................................................................52
Figure 2:
Arm A Overview ....................................................................................................54
Figure 3:
Arm B Overview ....................................................................................................57
Figure 4:
Arm C Overview ....................................................................................................58
Figure 5:
Arm D Overview ....................................................................................................61
Figure 6:
Arm E Overview.....................................................................................................64
Figure 7:
Arm F Overview.....................................................................................................66
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1.
INTRODUCTION 
1.1.
Disease Background
1.1.1.
Non-Hodgkin Lymphoma
Non-Hodgkin lymphomas (NHLs) comprise a heterogeneous group of malignancies. Within 
Europe, the incidence of NHL is approximately 49,533 with a mortality of 20,347 (Ferlay, 2015). 
In the United States (US), it is estimated that approximately 72,580 new cases of NHL will be 
diagnosed and approximately 20,150 subjects will die of their disease in 2016 (Siegel, 2016). 
Non-Hodgkin lymphomas are classified according to the current World Health Organization 
(WHO) classification (Swerdlow, 2016) into immature lymphoid neoplasms, mature B-cell 
neoplasms, T cell and natural killer (NK)-cell neoplasms, and post-transplant 
lymphoproliferative disorders. Mature B-cell lymphomas are further classified into indolent 
lymphomas (eg, multiple myeloma (MM), chronic lymphocytic leukemia [CLL]) and aggressive 
lymphomas (eg, diffuse large B-cell lymphoma [DLBCL]). 
DLBCL is the most frequent lymphoma subtype, representing approximately 30% of all NHL. 
DLBCL can develop de novo or secondary to transformation of an indolent NHL. Estimated 
incidence in the European Union (EU) is 3 to 4/100,000/year, increasing with age from 
0.3/100,000/year (35 to 39 years) to 26.6/100,000/year (80 to 84 years) (Tilly, 2012). About 
10,000 deaths per year are due to DLBCL in the US (National Cancer Institute [NCI]). Most 
subjects with localized DLBCL can be cured with conventional combination immuno-chemo- or 
combined-modality therapy (Tilly, 2015). For subjects with advanced-stage disease, the majority 
of subjects can be cured with doxorubicin-based combination chemotherapy and rituximab (eg, 
R-CHOP). Prognosis depends on individual risk factors. The International Prognostic Index (IPI) 
for aggressive NHL includes five significant risk factors prognostic of overall survival (OS): 
Subject age, serum lactate dehydrogenase (LDH) level, Eastern Cooperative Oncology Group 
(ECOG) performance status, disease stage, and extranodal involvement. Subjects with ≥ 2 risk 
factors after age-adjustment have a poor prognosis with a 5-year OS-rate of 21% to 46%. Age-
and stage-adjusted modifications are used for younger subjects with localized disease (Moller, 
2003). 
Despite overall improvement in outcomes of DLBCL, approximately one-third of subjects will 
develop relapsed/refractory (R/R) disease that remains a major cause of mortality. Refractory 
disease is defined as a < 50% decrease in lesion size or the appearance of new lesions. Relapsed 
disease reflects the (re)appearance of lesions after attainment of a partial or complete response 
(PR or CR) (Cheson, 2007). Relapsed/refractory subjects have a poor prognosis, particularly 
those who do not respond to second line chemotherapy with a median OS of 4.4 months (Van 
Den Neste, 2016). 
Diffuse large B-cell lymphoma is a heterogeneous disease with several histological and 
molecular subtypes. The largest subgroup is DLBCL not otherwise specified (NOS). Molecular 
profiling by gene expression profiling (GEP) based on biologic similarity to normal stages of B-
cell development (cell of origin [COO]) helped to further divide DLBCL into germinal center-
like (GCB), activated B-cell-like (ABC) tumors, and primary mediastinal large B-cell lymphoma 
(PMBCL), a distinct clinical entity (Lenz, 2008). Immunohistochemistry (IHC) algorithms are 
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clinically used to identify the COO and helped to identify ABC DLBCL as a high-risk subtype 
less likely to respond to standard immune-chemotherapy.
Within the GCB group a specific high-risk group is defined by concurrent chromosomal 
rearrangements of c-MYC and the anti-apoptotic oncogene BCL2 or BCL6, referred to as 
double-hit lymphomas (DHL). In addition, in some cases there is a concurrent rearrangement of 
c-MYC and both antiapoptotic oncogenes BCL2 and BCL6, which are referred to as triple-hit 
lymphoma. DHL represents approximately 5% of de novo cases of DLBCL with very poor OS of 
≤12 months when treated with R-CHOP (Camicia, 2015). Newer data suggest negative 
prognostic impact of P53 mutations or deletions in DLBCL (Schiefer, 2015).
Despite follicular lymphoma (FL) being an indolent lymphoma type, Grade 3B FL is regarded as 
aggressive lymphoma. Clinical behavior is very similar to DLBCL and FL frequently undergoes 
histological transformation into DLBCL. Consequently, current guidelines recommend to treat 
FL Grade 3B according to the DLBCL treatment algorithm (NCCN, 2016; Dreyling, 2014). 
These subjects are generally treated with an anthracycline-based chemotherapy combined with 
rituximab (eg, R-CHOP) and have a similar prognosis to that of de novo DLBCL. 
1.1.2.
CD19 as a Therapeutic Target 
CD19 is a 95-kDa glycoprotein present on B-cells from early development until differentiation 
into plasma cells (Stamenkovic, 1988). It is a member of the immunoglobulin superfamily and a 
component of a B-cell surface signal transduction complex that positively regulates signal 
transduction through the B-cell receptor (Stamenkovic, 1988; Brentjens, 2011). 
CD19 is an attractive therapeutic target because it is expressed by most B-cell malignancies, 
including B-cell NHL (Li, 1993; Li, 1996; Davila, 2012). Importantly, the CD19 antigen is not 
expressed on hematopoietic stem cells or on any normal tissue apart from those of the B-cell 
lineage. 
1.1.3.
CD19–Targeted Chimeric Antigen Receptors 
CD19-specific chimeric antigen receptors (CARs) are single chain variable fragments (scFv) 
fused to a transmembrane domain and cytoplasmic signaling domains. Expression of the CD19-
CAR in autologous T cells is achieved by ex vivo transduction using a recombinant retroviral or 
lentiviral vector. The CAR is expressed on the T cell surface and redirects the transfected T cells 
to CD19-expressing lymphoma cells, leading to CD19-specific tumor cell recognition, lysis, 
cytokine secretion and T cell proliferation (Sadelain, 2013). In clinical studies, CD19-targeted 
CARs have demonstrated encouraging activity in adult and pediatric subjects with R/R B-cell 
acute lymphoblastic leukemia (ALL) and B-cell NHL (Maude, 2018; Park, 2018; Gardner, 2017;
Turtle, 2016; Schuster, 2017; Neelapu, 2017). 
1.2.
Compound Background 
1.2.1.
JCAR017 Investigational Drug Product
The JCAR017 (lisocabtagene maraleucel; liso-cel) investigational drug product is a novel, 
CD19-targeted, genetically modified, autologous, defined composition, T cell immunotherapy.
JCAR017 is manufactured from autologous peripheral blood mononuclear cells (PBMCs) that 
are obtained via standard leukapheresis collection procedures. The PBMCs undergo sequential 
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positive selection for CD8+ and CD4+ T cells where the CD4 and CD8 purified T cell 
populations derived from the same starting material (leukapheresis) are separated, subsequently 
cryopreserved, transduced with CAR and expanded through parallel processing in order to 
ensure the final product is infused to the subjects in a defined cell composition. The CD19-
specific CAR consists of an scFv binding domain derived from a murine CD19-specific 
monoclonal antibody (mAb; FMC63) and the 4-1BB and CD3ζ signaling domains. The truncated 
human epidermal growth factor receptor (EGFRt) protein is co-expressed with the CD19-specific 
CAR as a cell surface protein for analytical detection of transduced T cells. The JCAR017 drug 
product is provided as two individually formulated CD8+CAR+ and CD4+ CAR+ T cell 
suspensions in media containing dimethyl sulfoxide (DMSO) that are thawed and administered 
separately by intravenous (IV) infusion.
Please refer to the JCAR017 Investigator’s Brochure (IB) for detailed information concerning the 
available pharmacology, toxicology, clinical studies, and adverse event (AE) profile of the 
investigational product (IP).
1.2.2.
Durvalumab (MEDI4736)
Durvalumab (MEDI4736, Durva) is a human immunoglobulin G (IgG)1 kappa monoclonal 
antibody (mAb) directed against human programmed cell death ligand 1 (PD-L1) protein. 
Durvalumab is expressed in Chinese hamster ovary cells and has an overall molecular weight of 
approximately 149 kDa. Durvalumab selectively binds human PD-L1 with high affinity and 
blocks its ability to bind to programmed cell death 1 (PD-1) protein and cluster of differentiation 
(CD)80. The fragment crystallizable (Fc) domain of durvalumab contains a triple mutation in the 
constant domain of the IgG1 heavy chain that reduces binding to the complement component 
C1q and the Fc gamma receptors responsible for mediating antibody-dependent T cell-mediated 
cytotoxicity (ADCC) (Oganesyan, 2008; Ibrahim, 2015).
On 01 May 1, 2017, the US Food and Drug Administration (FDA) granted accelerated approval 
to durvalumab (IMFINZI™) for the treatment of patients with locally advanced or metastatic 
urothelial carcinoma who have disease progression during or following platinum-containing 
chemotherapy or who have disease progression within 12 months of neoadjuvant or adjuvant 
treatment with platinum-containing chemotherapy.
Refer to the durvalumab IB for detailed information concerning the available pharmacology, 
toxicology, drug metabolism, clinical studies, and AE profile of the IP.
1.2.3.
CC-122 (Avadomide)
CC-122 is a nonphthalimide analog of thalidomide that retains binding affinity to a protein called 
cereblon (CRBN) (encoded by the CRBN gene), a member of the Cullin 4-ring ligase complex. 
In T cells, CC-122 binds to cereblon and promotes targeted degradation of the protein Aiolos, a 
transcriptional repressor of T cell activation. It is in part via the degradation of Aiolos that 
CC-122 exerts its T cell activation function.CC-122 has multiple activities, which include: 
immune modulation of several immune cell subsets such as monocytes, T cells, B-cells, and 
natural killer (NK) cells; antiproliferative activity in multiple tumor types including DLBCL, 
mantle cell lymphoma (MCL), FL, CLL, and MM represented by multiple cell lines; antigrowth 
activity in human cancer cells (HCC); and antiangiogenic activity as demonstrated by inhibition 
of endothelial cell sprout formation, growth factor induced endothelial cell migration and 
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Protocol JCAR017-BCM-002 Amendment 6 Final: 27 Jan 2021
Refer to the current ibrutinib package insert (Imbruvica US PI) for detailed information 
concerning the available pharmacology, toxicology, drug metabolism, clinical studies, and AE 
profile of the IP.
1.2.6.
Relatlimab
Relatlimab (BMS-986016) is a fully human lymphocyte activation gene 3 (LAG-3) specific 
antibody that was isolated following immunization of transgenic mice expressing human 
immunoglobulin (Ig) genes. Relatlimab binds to LAG-3 receptors expressed on T-cells with high 
affinity and prevents binding of this receptor to cells bearing its ligands, major histocompatibility 
complex (MHC) Class II (Andrews, 2017) and fibrinogen-like protein 1 (FGL-1) (Wang, 2019).
Relatlimab binding inhibits the negative regulatory function of LAG-3 mediated through its 
interaction with ligands in vitro. By blocking the inhibitory LAG-3 signaling pathway, relatlimab 
enhances the anti-tumor immune response and, thus, has the potential to inhibit the growth of 
multiple malignancies when administered alone or in combination with other therapeutic 
immuno-oncology (IO) agents. 
Refer to the current Relatlimab IB for detailed information concerning the available 
pharmacology, toxicology, drug metabolism, and clinical safety profile of relatlimab.
1.2.7.
Nivolumab 
Nivolumab (also referred to as BMS-936558, MDX1106, or ONO-4538) is a human monoclonal 
antibody (HuMAb; immunoglobulin G4 [IgG4]-S228P) that targets the programmed death-1 
(PD-1) cluster of differentiation 279 (CD279) cell surface membrane receptor. PD-1 is a negative 
regulatory molecule expressed by activated T and B lymphocytes. Binding of PD-1 to its ligands, 
programmed death–ligands 1 (PD-L1) and 2 (PD-L2), results in the down-regulation of 
lymphocyte activation. Inhibition of the interaction between PD-1 and its ligands promotes 
immune responses and antigen-specific T-cell responses to both foreign antigens as well as self-
antigens. Nivolumab is expressed in Chinese hamster ovary (CHO) cells and is produced using 
standard mammalian cell cultivation and chromatographic purification technologies. The clinical 
study product is a sterile solution for parenteral administration. Nivolumab (OPDIVO™) is 
approved for the treatment of several types of cancer in multiple regions including the United 
States (US, Dec-2014), the European Union (EU, Jun-2015), and Japan (Jul-2014). Dual 
checkpoint inhibition with relatlimab and nivolumab results in enhanced T-cell effector function 
that is greater than the effects of either antibody alone in murine syngeneic tumor models.
Refer to the current nivolumab IB for detailed information concerning the available 
pharmacology, toxicology, drug metabolism, and clinical safety profile of nivolumab.
1.2.8.
CC-99282 
CC-99282 is a an oral cereblon-modulating agent (CELMoD) that is initially being developed for 
the treatment of patients with R/R NHL and CLL. Cereblon functions as a substrate receptor for 
a CRL4 ubiquitin E3 ligase (Ito, 2010; Lopez-Girona, 2012; Chamberlain, 2014) and the binding 
of cereblon modulating compounds induces the recruitment, ubiquitination, and destruction of 
key target substrates (eg, Ikaros family zinc finger proteins 1 and 3 [IKZF1 and IKZF3, aka 
Ikaros and Aiolos]) to mediate cellular effects (Gandhi, 2014; Krönke, 2014; Lu, 2014; An, 
2017).
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while higher overall response rates of up to 80 % (CR rate 47% to 60%) have been reported after 
CAR T cell infusion, responses in some are transient and subjects have been shown to relapse in 
the presence of persistent CAR T cells (Neelapu, 2017; Abramson, 2017). Another study 
reported a long term CR rate of 40% (Schuster, 2017). 
Possible explanations for this are (Tran, 2017):

Immunological exhaustion of circulating T cells and/or changes in T lymphocyte 
populations.

An effect of the tumor microenvironment, eg, CAR T cells are suppressed by the 
lymphoma microenvironment and lose their antitumor activity before they are able to 
eliminate all lymphoma cells.
Accordingly, combination of JCAR017 with immune system modifiers such as checkpoint 
inhibitors or immunomodulatory compounds could restore the T cell function, reduce the 
immunosuppressive tumor microenvironment, and improve the response and durability of the 
response to JCAR017. In order to enhance the antitumor activity of JCAR017, this trial will test 
if the combination of JCAR017 with immunomodulatory agents is safe and improves the CRR 
and the durability of responses. 
1.3.2.
Rationale for the Study Design
To test the above assumptions, this trial uses a multi-arm, parallel cohort design to test various 
combinations of JCAR017 with different combination agents. Each combination will be tested in 
a dedicated study arm. Each study arm may test three general sequences of treatment in separate 
cohorts (see Figure 1):

A post-expansion cohort will assess the safety and feasibility of boosting the 
JCAR017 efficacy after peak expansion of JCAR017, ie, after the first efficacy 
assessment around Day 29 post-JCAR017 infusion. 

A post-infusion cohort will assess the safety and feasibility of administering 
combination agents closer to peak expansion of JCAR017 (ie, within the first 2 
weeks) with the intent to increase T cell health, modulate the tumor 
microenvironment and optimize T cell subpopulations following JCAR017 infusion 
and prior to peak expansion of JCAR017. 

A pre-infusion cohort will test the safety and feasibility of initiating treatment with a 
combination agent prior to JCAR017 infusion. This may increase the health of T cells 
in the primary leukapheresis starting material and translate into a healthier JCAR017 
T cell product and potentially modulate the tumor microenvironment to make the 
tumor more susceptible to the JCAR017. Continuing the combination post infusion 
may potentially improve the pharmacodynamics of JCAR017 cells, ultimately 
improving efficacy and safety of JCAR017.
Additional cohorts may be added with the aim to combine approaches to maximize the efficacy 
of JCAR017 pending safety and preliminary efficacy results to further optimize JCAR017 
efficacy. 
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Protocol JCAR017-BCM-002 Amendment 6 Final: 27 Jan 2021
This modular trial design allows parallel testing of different doses and schedules of novel 
combinations to improve clinical efficacy of JCAR017. 
1.3.3.
Rationale for Dose, Schedule and Regimen Selection 
1.3.3.1.
JCAR017 Dose Rationale
JCAR017 has been generally tolerated at doses from 0.5 x 106 to 1 x 106 CAR+ T cells/kg in 
pediatric subjects with ALL conditioned with flu/cy. The maximum tolerated dose (MTD) was 
exceeded in this study in subjects treated after flu/cy LD chemotherapy: at 5 x 106 CAR+ T 
cells/kg in pediatric subjects with ALL (PLAT-02 study). Antitumor activity has been observed 
at all doses of JCAR017 tested. 
The JCAR017 starting dose for Arm A is a dose of 50 x 106 CAR+ T cells (dose level 1 [DL1]), 
which converts in CAR+ T cells per kg to the middle of the dose ranges tolerated with JCAR017: 
50 x 106 CAR+ T cells is equivalent to 0.5 x 106 CAR+ T cells/kg for a 100 kg adult and 
equivalent to 1 x 106 CAR+ T cells/kg for a 50 kg adult. 
Dose level 2 (DL2) (100 x 106 CAR+ T cells) was also identified in Study 017001 to be safe and 
will be tested in this trial in Cohort 1B in Arm A and used as starting dose level for subsequent 
arms.
This trial will employ LD chemotherapy prior to the JCAR017 infusion with flu/cy (see 
Section 7.2.1 for dose details).
1.3.4.
Rationale for Choice of Combination Compounds 
As a monotherapy, CD19-targeted CAR T cells have been tested in adult subjects with 
aggressive B-cell NHL with a high overall response rate (ORR), but a lower than desirable rate 
of durable CR. Checkpoint proteins, inhibitory microenvironment factors and T cell intrinsic 
factors may decrease the function of the modified T cells in subjects with aggressive B-cell 
NHL, thereby limiting CAR T cell-mediated antitumor activity. Compounds that either disrupt 
inhibitory microenvironment factors or enhance the intrinsic biological activity of the JCAR017 
cells offer an opportunity to enhance the potency and persistent efficacy of JCAR017 while 
maintaining acceptable safety and tolerability.
1.3.4.1.
Rationale for JCAR017 in Combination with PD-1 or PD-L1 Blockade
CD8+ cytotoxic T cells recognition of target antigen presented on tumor cells involves formation 
of the immune synapse that induces activation and initiates tumor-cell killing after. Subsequent 
to activation, T cells express PD-1 on their surface and secrete interferons that in turn induce 
expression of checkpoint inhibitors such as PD-L1 and PD-L2 (Garcia Diaz, 2017) on tumor 
cells and bystander cells (Hoekstra, 2020). Binding of PD-L1 and/or PD-L2 on tumor cells
(including lymphoma) and the tumor microenvironment to PD-1 on T cells (including CAR T 
cells) results in inhibitory checkpoint signaling that decreases cytotoxicity and leads to T cell 
exhaustion (Andorsky, 2011). High levels of PD-L1 promote T cell exhaustion, and PD-L1 
blockade reinvigorates T cell function. 
Expression of PD-1 / PD-L1 axis has been detected in various lymphomas. It is well established 
that tumor-infiltrating lymphocytes (TILs) express PD-1, 
 
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2.
STUDY OBJECTIVES AND ENDPOINTS
Table 1:
Study Objectives
Note: “Combination agent” refers to the specific agent being tested in combination with 
JCAR017 within each arm. 
Primary Objectives
The primary objectives of the study are:
Dose finding (Phase 1):

To evaluate the safety and to define the recommended Phase 2 dose and schedule (RP2D) of 
JCAR017 combinations in adult subjects with relapsed/refractory (R/R) aggressive B-cell 
non-Hodgkin lymphoma (NHL)
Dose expansion (Phase 2):

To evaluate the efficacy of JCAR017 combinations in adult subjects with R/R aggressive B-
cell NHL defined as complete response rate (CRR)
Secondary Objectives
The secondary objectives are: 
Dose finding (Phase 1):

To assess the efficacy of JCAR017 combinations 
Dose expansion (Phase 2):

To assess the safety and other efficacy parameters of JCAR017 combinations 

To characterize changes in health-related quality of life (HRQoL) outcome measures for 
subjects treated with JCAR017 combinations
Phase 1/2:

To characterize the pharmacokinetic (PK) profiles of JCAR017

To characterize the PK profile of the respective combination agents
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Table 1:
Study Objectives (Continued)
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Table 2:
Study Endpoints
Endpoint
Name 
Description
Timeframe
Primary:
Dose 
finding 
(Phase 1)
Dose-limiting 
toxicity (DLT) 
rates
Percentage of subjects having a 
DLT 
From first dose of the 
combination agent until 1 
month (28 days) after 
JCAR017 infusion (pre-
JCAR017 cohort) or from 
JCAR017 infusion until 1 
month (28 days) after the 
first dose of combination 
agent (post-JCAR017 
cohort) 
Primary:
Dose 
expansion 
(Phase 2)
Complete response 
rate (CRR)
Percentage of subjects achieving a 
complete response (CR) according 
to the Lugano Classification 
(Cheson, 2014) by local review
At 3 months post-JCAR017 
infusion and subsequently at 
6 months post-JCAR017 
infusion
Secondary: 
Dose 
finding 
(Phase 1)
Complete response 
rate (CRR)
Percentage of subjects achieving a 
complete response (CR) according 
to the Lugano Classification 
(Cheson, 2014) by local review
At 3 months post-JCAR017 
infusion and subsequently at 
6 months post-JCAR017 
infusion
Secondary:
Dose 
expansion 
(Phase 2)
Health-related 
quality of life 
(HRQoL) 
HRQoL parameters assessed by 
European Organisation for 
Research and Treatment of Cancer 
– Quality of Life C30 questionnaire 
(EORTC-QLQ-C30) or European 
Quality of Life-5 Dimensions 
health state classifier to 5 Levels 
(EQ-5D-5L)
Up to 24 months post-
JCAR017 infusion
Secondary 
(Phase 1/2)
Safety 
Type, frequency, and severity of 
adverse events (AEs) and 
laboratory abnormalities 
Up to 3 months after the 
dose of JCAR017 or after 
the last dose of the 
combination agent, 
whichever occurs last
Efficacy:
Progression-free 
survival (PFS)
Time from start of JCAR017, to 
progressive disease (PD) or death 
from any cause
Up to 24 months post-
JCAR017 infusion
Secondary 
(Phase 1/2)
Efficacy:
Overall survival 
(OS)
Time from start of JCAR017 to 
time of death from any cause
Up to last subject last visit 
Efficacy:
Overall response 
rate (ORR)
Percentage of subjects achieving an 
objective response of partial 
response (PR) or better according 
to the Lugano Classification 
(Cheson, 2014) 
At 1, 3, 6, 9, 12, 18 and 24 
months post-JCAR017 
infusion
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Endpoint
Name 
Description
Timeframe
Efficacy:
Duration of 
response (DOR)
Time from first response to disease 
progression or death from any 
cause
Up to 24 months post-
JCAR017 infusion
Table 2:
Study Endpoints (Continued)
Endpoint
Name 
Description
Timeframe
Efficacy:
Event-free 
survival (EFS)
Time from start of JCAR017 to death 
from any cause, disease progression, 
or starting a new anti-lymphoma 
therapy, whichever occurs first
Up to 24 months post-
JCAR017 infusion
Secondary 
and 
Exploratory 
(Phase 1/2)
Pharmacokinetic 
(PK)
Maximum concentration (Cmax), time 
to maximum concentration (Tmax), 
area under the curve (AUC), and 
other relevant PK parameters of 
JCAR017 and the combination agent
Up to 24 months post-
JCAR017 infusion
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3.
OVERALL STUDY DESIGN
3.1.
Study Design
This study is intended to evaluate various drug combinations with JCAR017, as separate arms, 
over the life of the protocol, using the same objectives. Each combination will be evaluated 
separately (ie, the intention is not to compare between combinations) for the purposes of the 
objectives, trial design and statistical analysis. The following combinations will be tested:

Arm A: JCAR017 in combination with durvalumab

Arm B: JCAR017 in combination with CC-122

Arm C: JCAR017 in combination with CC-220

Arm D: JCAR017 in combination with ibrutinib

Arm E: JCAR017 in combination with relatlimab and/or nivolumab

Arm F: JCAR017 in combination with CC-99282 
Additional arms will be added by way of amendment once combination agents have been 
selected. Within each arm, cohorts and subcohorts will test different doses and schedules of the 
combination agent(s).
The study will consist of 2 parts: dose finding (Phase 1) and dose expansion (Phase 2).
3.1.1.
Phase 1 
The study started with one combination arm, Arm A. Arm B was added by protocol 
amendment 2 (28 Feb 2018) and Arms C and D added by protocol amendment 4 (29 Oct 2020). 
Arms E and F are added by protocol amendment 6. Other combination arms may be opened at a 
later stage via a protocol amendment.
Within each combination arm, up to 3 cohorts plus various subcohorts (eg, additional dose levels 
and schedules) may be tested (Figure 1). Subcohorts may test several dose levels of JCAR017 
and the combination agent(s) and the optimal time to start the combination agent(s). Details on 
individual subcohorts will be provided in the respective study arm description.
The post-expansion cohort will assess the safety and feasibility of boosting the JCAR017 
efficacy with combination agent(s) after peak expansion of JCAR017, ie, after the first efficacy 
assessment around Day 29 post-JCAR017 infusion. 
The post-infusion cohort will assess the safety and feasibility of administering combination 
agents closer to peak expansion of JCAR017 with the intent to increase T cell health, modulate 
the tumor microenvironment and optimize T cell subpopulations following JCAR017 infusion
and prior to peak expansion of JCAR017 (ie, within the first 2 weeks). 
The pre-infusion cohort will test the safety and feasibility of initiating treatment with a 
combination agent prior to JCAR017 infusion. This may increase the health of T cells in the 
primary leukapheresis starting material and translate into a healthier JCAR017 T cell product and 
potentially modulate the tumor microenvironment to make the tumor more susceptible to the 
JCAR017. Continuing the combination post infusion may potentially improve the 
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Protocol JCAR017-BCM-002 Amendment 6 Final: 27 Jan 2021
pharmacodynamics of JCAR017 cells, ultimately improving efficacy and safety of the infused 
JCAR017.
Additional cohorts may be added with the aim to combine approaches to maximize the efficacy 
of JCAR017. 
Figure 1:
High Level Study Design 
= combination agent; LD = lymphodepleting.
a One study arm will test a given combination of JCAR017 with an agent. The timing of the combination relative to JCAR017 
infusion may be tested in one or more cohorts.
b Subcohorts may evaluate different dose levels or schedules of JCAR017 or combination agent within a cohort.
The Bayesian Optimal Interval Design (BOIN) (Liu, 2015; Yuan, 2016) will be used for dose 
escalation/de-escalation decision during Phase 1.
Subjects must have elevated disease burden at screening (sum of product of perpendicular 
diameters (SPD) of up to 6 index lesions ≥ 25 cm2 by CT scan). Arms A and B are not subject to 
this requirement. Up to 15% of subjects per subcohort (ie, 1 in Phase 1 and 4 in an expansion 
cohort) may have Richter’s transformation (transformed chronic lymphocytic leukemia/CLL) 
without elevated tumor burden.
Enrollment will be staggered such that the first 6 subjects within a subcohort will enter the dose-
limiting toxicity (DLT) period a minimum of 1 week apart (or longer as specified in the relevant 
arm) to allow appropriate safety monitoring. Dose-limiting toxicities will be assessed during the 
DLT period defined per arm (see Section 9.3.1). A RP2D will be established based on the 
tolerability and preliminary efficacy in the DLT evaluable subjects treated in the respective 
subcohort. The final number of subjects will depend on the number of dose levels and schedules 
tested and the number of DLTs observed within each subcohort. Non-DLT evaluable subjects 
will be replaced.
A safety review committee (SRC) whose members include the medical monitor(s), drug safety 
physician, statistician, and a subset of investigators will determine a RP2D for each combination 
treatment arm based on an integrated assessment of the safety, PK, Pd data, and preliminary 
efficacy information. The SRC may override the BOIN algorithm for safety concerns.
As a general rule, in post-JCAR017 cohorts JCAR017-related severe toxicities must have 
resolved before the combination agent is started. Detailed rules are described in the individual 
study arms. 
Within an arm and cohort, a dose level or schedule (subcohort) shown to be safe in Phase 1 may 
be expanded in Phase 2. The decision to expand a particular subcohort will be made by the 
Sponsor upon recommendation by the SRC after review of all available data. Enrollment will 
stop when approximately 35 subjects are evaluable for safety and response at the dose and 
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schedule chosen as a RP2D (ie, 9 in Phase 1 and 26 in Phase 2). After 6 subjects have been 
treated at the RP2D in the expansion cohort further enrollment rules will be determined by the 
Sponsor considering the recommendation of the SRC.
3.1.2.
All Phases
All subjects from both phases and all cohorts will be followed for AEs (including new 
malignancies) and concomitant medications/ procedures for at least 3 months after JCAR017 
infusion. Safety follow-up for a given combination agent will be detailed in the respective study 
arm description and may increase the safety follow-up period.
All subjects from Phase 1 and Phase 2 will be followed for 24 months following JCAR017 
infusion for disease status, treatment related AEs, and until the last subject last visit for survival. 
Post-study follow-up for survival, relapse, long-term toxicity (including new malignancies), and 
viral vector safety will continue under a separate long-term follow-up (LTFU) protocol for up to 
15 years after the JCAR017 dose as per health authority regulatory guidelines.
The study will be conducted in compliance with the International Council for Harmonisation 
(ICH) of Technical Requirements for Registration of Pharmaceuticals for Human Use/Good 
Clinical Practice (GCP) and applicable regulatory requirements.
3.1.3.
Study Arm A (JCAR017 in Combination with Durvalumab)
Arm A will evaluate the safety and efficacy of JCAR017 in combination with durvalumab. 
Subjects from both phases and all cohorts who reach a PR 3 months after JCAR017 infusion may 
continue durvalumab until progression for a maximum total duration of 12 months. Agreement 
must be obtained from the Sponsor. 
3.1.3.1.
Durvalumab Dose Rationale
The dose levels and treatment schedules for durvalumab are based on a safe dose established in 
Study CD-ON-MEDI4736-1108, a Phase 1/2a study to evaluate the safety, tolerability, and PK 
of durvalumab in subjects with advanced solid tumors and on population PK analyses. 
Population PK analysis indicated only a minor impact of body weight on the PK of durvalumab 
(coefficient of ≤ 0.5). The impact of body weight-based (10 mg/kg every 2 weeks [Q2W]) and 
fixed dosing (750 mg Q2W) of durvalumab was evaluated by comparing predicted steady state 
PK concentrations using the population PK model. A fixed dose of 750 mg and 1500 mg was 
selected to approximate 10 mg/kg and 20 mg/kg, respectively (based on median body weight of 
approximately 75 kg). A total of 1000 subjects were simulated using a body weight distribution 
of 40 to 120 kg. Simulation results demonstrated that body weight-based and fixed dosing 
regimens yield similar median steady state PK concentrations with slightly less overall between-
subject variability with the fixed dosing regimen. Based on these results the dose of 1500 mg 
every 4 weeks (Q4W) is now being explored as a dose that provides continuous plasma 
concentration of antibody above the threshold needed for in vitro activity. The dose of 1500 mg 
Q4W is the RP2D across the durvalumab clinical program (for ongoing or planned studies in 
both solid tumors and hematologic malignancies). Over 1000 subjects with solid tumors and 
myelodysplastic syndrome were treated at a dose schedule equivalent to 1500 mg Q4W (ie, 10 
mg/kg Q2W or 20 mg/kg Q4W which show similar exposure levels based on the area under the 
curves steady state), and available safety data support this as an appropriate dose for durvalumab 
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Protocol JCAR017-BCM-002 Amendment 6 Final: 27 Jan 2021
in this study. Extrapolation from the PK simulations defined a dose of 375 mg every week 
(Q1W) as expected to be equivalent to a dose of 5 mg/kg Q1W, which is believed to be 
comparable to a dose of 10 mg/kg Q2W and 20 mg/kg Q4W. Please refer to the durvalumab IB 
for further information.
Arm A Cohort 1 (post-JCAR017) will evaluate the safety and efficacy of starting durvalumab 
approximately Day 29 after infusion of JCAR017. Durvalumab will be administered at a dose of 
375 mg Q1W for 2 weeks, then one dose of 750 mg Q2W, followed by 1500 mg Q4W. This 
dosing approach is based on PK simulations which show similar biological PD-L1 occupancy 
but shorter half-life at lower doses. See below Figure 2 and Table 3 for arm and cohort details 
and dose schedule. Please refer to for dose escalation/ de-escalation rules.

Cohort 1A will use JCAR017 DL1 (50 x 106 CAR+ T cells) 

Cohort 1B will use JCAR017 DL2 (100 x 106 CAR+ T cells) 

Cohort 1A-1 will use JCAR017 DL1 (50 x 106 CAR+ T cells) and lower doses of 
durvalumab 

Cohort 1A-2 will use JCAR017 DL1 (50 x 106 CAR + T cells) and delayed doses of 
durvalumab 
All subjects will be followed for AEs and concomitant medications/procedures for 3 months 
after the JCAR017 infusion and 3 months after the last dose of durvalumab, whichever occurs 
later. After this period, all subjects will be followed until 24 months after JCAR017 infusion for 
treatment related AEs and concomitant medications/procedures. 
Figure 2:
Arm A Overview
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Abbreviations: D = day; LD chemo = lymphodepleting chemotherapy.
Table 3:
Arm A Dosing Schedule
Cohort
JCAR017 Dose
Durvalumab Dose
Durvalumab Schedulea
1A
50 x 106
CAR+T cells
(Dose level 1)
375 mg
Days 29 and 36 post-JCAR017 infusion
750 mg
Day 43 post-JCAR017 infusion
1500 mg
Days 57 and 85 post-JCAR017 infusion
1B
100 x 106
CAR+T cells
(Dose level 2)
375 mg
Days 29 and 36 post-JCAR017 infusion
750 mg
Day 43 post-JCAR017 infusion
1500 mg
Days 57 and 85 post-JCAR017 infusion
1A-1
50 x 106
CAR+T cells
(Dose level 1)
225 mg
Days 29 and 36 post-JCAR017 infusion
375 mg
Days 43 and 50 post-JCAR017 infusion
750 mg
Days 57 and 71 post-JCAR017 infusion
1500 mg
Day 85 post-JCAR017 infusion
1A-2
50 x 106
CAR+T cells
(Dose level 1)
375 mg
Days 43 and 50 post-JCAR017 infusion
750 mg
Days 57 and 71 post-JCAR017 infusion
1500 mg
Day 85 post-JCAR017 infusion
a Start date of durvalumab can be within 7 days of planned Day 29. In case of an earlier or later start (eg, Day 22), 
the next dosing dates should be rescheduled accordingly: in case durvalumab is started on Day 22 (375 mg), next 
dose (375 mg) would be 7 days after (Day 29), next dose (750 mg) would be 7 days later (Day 36), next dose 
(1500 mg) would be 2 weeks later (Day 50) and the last planned dose would be 4 weeks later (Day 78).
In case treatment with durvalumab is continued beyond Day 85 (see Section 3.1.3 for conditions 
and Section 6.3.1.1 for safety follow-up details), the subsequent doses should be given every 4 
weeks at 1500 mg for a maximum total duration of 12 months. 
3.1.4.
Study Arm B (JCAR017 in Combination with CC-122)
Arm B will evaluate the safety and efficacy of JCAR017 in combination with CC-122. 
Subjects who reach a PR or SD 6 months (Day 180) after JCAR017 infusion may continue 
CC-122 until progression or for up to Month 24, whatever is earlier. Agreement must be 
obtained from the Sponsor. 
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3.1.4.1.
CC-122 Dose Rationale
CC-122 has shown preclinical activity and promising early clinical activity in R/R DLBCL. Dose 
levels selected for evaluation in Phase 1 target efficacious doses of CC-122 evaluated in the R/R 
setting. In addition, a candidate patient selection gene expression-based signature was associated 
with improved response rates in the selected population with R/R DLBCL. Preclinical data 
indicated that CC-122 is about 10 times more potent than lenalidomide in terms of 
immunomodulatory activities in T cells and NK cells (Gandhi, 2012) and is 5 to 10 times more 
potent in terms of anti-proliferative activity in a panel of human CLL cells (Hagner, 2014). 

All Cohorts will use JCAR017 DL 2 (100 x 106 CAR+ T cells) 
Subjects will receive CC-122 continuously on 5 of 7 days until Day 180 (Month 6). All subjects 
will be followed for AEs and concomitant medications/procedures for 3 months after the 
JCAR017 infusion and 28 days after the last dose of CC-122, whichever occurs later. After this 
period, all subjects will be followed until 24 months after JCAR017 infusion for treatment 
related AEs and concomitant medications/procedures. 
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experiencing a DLT after CC-122 administration, the CC-122 will be paused and may be 
resumed after dose adjustment (see Table 27).
According to the BOIN algorithm, escalation to Cohort 1B (CC-122 dose of 3 mg) or de-
escalation to Cohort 1A-1 (CC-122 dose of 1 mg) may occur (see Table 9). The decision will be 
taken based on the results from Cohort 1A by the Sponsor considering the SRC recommendation.
The lower dose of 1 mg may be explored if recommended by the SRC. 
3.1.9.3.
Arm C
Subjects in Arm C will receive JCAR017 at DL2.
In the initial subcohort 1A if no severe toxicities to JCAR017 occur, CC-220 will be started 
around Day 15 (+ 3 days). Delay of first dose of CC-220 of more than 3 days (eg, Day 19 for 
subcohort 1A) necessitates discussion with the Sponsor. Delay of subsequent CC-220 doses also 
needs discussion with the Sponsor. Subjects who do not receive CC-220 within 3 days of their 
scheduled start will not be evaluable for DLT and will be replaced. In subjects experiencing a 
DLT after CC-220 administration, CC-220 will be paused and may be resumed after dose 
adjustment (see Appendix S). In case of severe CRS or NT, CC-220 must be paused until 
resolution.
At Day 29 subjects with Grade 4 neutropenia, Grade 3 neutropenia associated with fever, or 
Grade 4 thrombocytopenia at the scheduled start of CC-220 will not restart until recovered to 
Grade < 3 without fever. If other toxicities to JCAR017 develop, CC-220 will not be started until 
AEs have resolved to baseline. The same rules apply for all other subcohorts.
Based on the results of the combination including safety and laboratory data, and according to 
the BOIN algorithm (see Table 9), escalated or de-escalated starting doses of CC-220 and an
earlier start of combination therapy may be evaluated. The starting CC-220 dose may be 
escalated to 0.6 mg or de-escalated to 0.3 mg and the start of CC-220 may be advanced to Day 8 
(+ 3 days) or Day 1 (+ 3 days). The decision on which subsequent subcohort will be selected will 
be taken by the Sponsor considering the SRC recommendation from the previous subcohort.
3.1.9.4.
Arm D
Subjects in Arm D will receive JCAR017 at DL2.
For subjects in the single subcohort 1A, ibrutinib will start at least 5 days prior to leukapheresis 
and continue until the day before LD chemotherapy and restarted the day after LD chemotherapy 
is completed. Delay of more than 7 days to restarting necessitates discussion with the Sponsor. 
Delays of subsequent ibrutinib doses require discussion with the Sponsor. In case of severe CRS 
or NT, ibrutinib must be paused until resolution.
In subjects experiencing a DLT after ibrutinib administration post-JCAR017, ibrutinib will be 
paused and may be resumed after dose adjustment (see Appendix T).
No additional subcohorts with alternative schedules, dose escalation or dose de-escalation are
planned in Arm D.
3.1.9.5.
Arm E
Subjects in Arm E will receive JCAR017 at DL2.
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In the initial cohort 1A, if no severe toxicities to JCAR017 (ie, Grade ≥3 CRS or NT) occur, 
checkpoint inhibitor therapy with relatlimab and/or nivolumab (CPI) will be started around Day 
8 (+ 4 days). If severe toxicities to JCAR017 develop, CPI will not be started until they have 
resolved to Grade ≤2. Delay of the first infusion of CPI of more than 4 days (ie, Day 12 for the 
initial subcohort) necessitates discussion with the Sponsor prior to administration. Delay of 
subsequent CPI doses also needs discussion with the Sponsor. Subjects who do not receive CPI
within 4 days of their scheduled start will not be evaluable for DLT and will be replaced. In 
subjects experiencing a DLT after CPI infusion, continuation of combination therapy after 
resolution of symptoms depends on the nature and severity of the adverse event (see Appendix C
for details).
In Phase 1 the first 3 subjects in each Arm E subcohort will enter the dose-limiting toxicity 
(DLT) period a minimum of 2 weeks apart; the next 3 subjects in the subcohort will enter the 
dose-limiting toxicity (DLT) period a minimum of 1 week apart. The first 6 subjects treated on 
the arm will be followed for safety to 90 days post JCAR017 before any decision on expansion is 
taken.
In Phase 1, subjects with a planned combination therapy start on Day 8 who do not receive CPI
within 4 days of their scheduled start will instead be treated on the schedule for Day 15 start (eg, 
a subcohort 1A patient would be treated per the 1A-1 schedule). Similarly, for planned start on 
Day 15, if unable to start by Day 19, initiate CPI on Day 22 and continue on Day 36, Day 57 and 
Day 85. These subjects will not be evaluable for DLT in the new subcohort and will be replaced. 
In Phase 2, subjects in subcohorts A+1, B+1 and C+1 (scheduled to start on Day 8 on a Q4W 
dose schedule) who cannot receive CPI within 4 days of their scheduled start will receive a Q2W 
dose on Day 15, or if still unable to start, Day 22. Subjects in subcohorts A+2, B+2 and C+2
(scheduled to start on Day 15 on a Q4W dose schedule) who cannot receive CPI within 4 days of 
their scheduled start will receive a Q2W dose on Day 22 or Day 29. If this occurs, sensitivity 
analyses will be performed to detect the impact on study results. 
Based on the results of the combination including safety and laboratory data, and according to 
the BOIN algorithm (see Table 9), subcohorts with escalated doses of relatlimab or no 
relatlimab, or a later start of combination therapy may be evaluated. The decision on which 
subsequent subcohort will be selected will be taken by the Sponsor considering the SRC 
recommendation from the previous subcohort.
Dose delay criteria apply for all drug-related adverse events regardless of whether the event is 
attributed to nivolumab or relatlimab or both.  Delay administration of both relatlimab (if 
scheduled) and nivolumab if the subject experiences severe toxicity to JCAR017 or if any of the 
delay criteria in Appendix C are met. Delay both relatlimab (if scheduled) and nivolumab dosing 
for any adverse event, laboratory abnormality, or intercurrent illness which, in the judgment of 
the investigator, warrants delaying the dose of study medication. 
For subjects who require delay of CPI, re-evaluate weekly, or more frequently, if clinically 
indicated and resume dosing when criteria to resume treatment are met (see Section 3.1.7). 
Continue tumor assessments per protocol even if dosing is delayed. Continue periodic study 
visits to assess safety and laboratory studies every week or more frequently if clinically indicated 
during such dosing delays.
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Subjects may resume treatment with study drug if they have completed AE management (eg, 
corticosteroid taper) or are on ≤ 20 mg prednisone or equivalent, and meet the requirements per 
Appendix C, and the delay to therapy is within the boundaries specified in Section 3.1.7.
CPI treatment must be permanently discontinued per criteria in Appendix C, Appendix D or
Appendix E.
Discontinue relatlimab and nivolumab for any AE, laboratory abnormality, or intercurrent illness 
which in the judgment of the Investigator, presents a substantial clinical risk to the subject with 
continued CPI dosing. Any event that leads to delay in CPI dosing lasting longer than 6 weeks 
requires discontinuation. 
3.1.9.6.
Arm F
Subjects in Arm F will receive JCAR017 at DL2
In the initial cohort 1A, if no severe toxicities to JCAR017 occur, CC-99282 will be started on 
Day 8 (+ 3 days). Delay of CC-99282 of more than 3 days (eg, after Day 11 for cohort 1A) 
necessitates discussion with the Sponsor. Delay of subsequent CC-99282 doses also requires 
discussion with the Sponsor. Subjects who do not receive CC-99282 within 3 days of their 
scheduled start will not be evaluable for DLT and will be replaced. In subjects experiencing a 
DLT after CC-99282 administration, CC-99282 will be paused and may be resumed after dose 
adjustment (Appendix U). In cases of Grade ≥3 CRS or NT, CC-99282 must be paused until 
resolution to Grade ≤2. 
Subjects with Grade ≥3 CRS or NT at the scheduled start of CC-99282 will be delayed until 
recovered to Grade ≤2. Subjects with uncontrolled infection will also not start CC-99282. If 
other toxicities to JCAR017 develop, CC-99282 will not be started until they have resolved to 
Grade ≤2. The same rules apply for all other sub-cohorts. Administration of growth factor is 
allowed (see Section 8.1.2).
Based on the results of the combination including safety and laboratory data, and according to 
the BOIN algorithm (see Table 9), escalated or de-escalated starting doses of CC-99282 and an 
earlier start of combination therapy may be evaluated. The starting dose of CC-99282 may be 
escalated to 0.4 mg or de-escalated to 0.2 mg and the start of CC-99282 may be advanced to 
Day 1 (+3 days) or adjusted to Day 15 (+3 days). The decision on which subsequent sub-cohort 
will be selected will be taken by the Sponsor considering the SRC recommendation from the 
previous subcohort.
3.1.9.7.
Dose Escalation and De-Escalation Rules
In Phase 1, decisions to move between dose levels (subcohorts) will be based on the BOIN 
algorithm in Table 9.
Expansion of a subcohort to Phase 2 evaluation requires a minimum of 6 subjects to have been 
evaluated for DLT at that dose level. Escalation between Phase 1 subcohorts requires a minimum 
of 3 subjects to have been evaluated for DLT at that dose level. De-escalation may be done with 
any number of prior subjects at that dose level.
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Table 9:
Dose Escalation and De-Escalation Rules Based on BOIN Algorithm
Action
The Number of Subjects Treated at the Current Dose Level
1
2
3
4
5
6
7
8
9
Target DLT rate = 0.3, λe=0.236, λd=0.358
Escalate if number 
of subjects with 
DLT is ≤
0
0
0
0
1
1
1
1
2
De-escalate if 
number of 
subjects with DLT 
is ≥
1
1
2
2
2
3
3
3
4
Eliminate if 
number of 
subjects with DLT 
is ≥
NA
NA
3
3
4
4
5
5
5
Abbreviations: BOIN = Bayesian optimal interval; DLT = dose-limiting toxicity.
3.2.
Stopping Rules
Adverse events and serious adverse events (SAEs) are expected to occur frequently in this study 
based on the subject population being accrued and on the nature of the advanced hematologic 
malignancy under study. Regular systematic review of SAEs will serve as the basis for pausing 
or prematurely stopping the study. Unexpected SAEs that are related to JCAR017 or the 
combination agent will be the primary criteria for pausing or stopping the study. Review of these 
SAEs, and any decision to pause enrollment or terminate the study, will be determined by the 
data safety monitoring board (DSMB), the Sponsor, and the medical monitor(s). Decisions to 
pause enrollment or terminate the study will be communicated promptly to Investigators, to the 
Institutional Review Boards (IRBs)/Independent Ethics Committees (IECs), Institutional 
Biosafety Committees (IBCs) (if applicable), and to the appropriate regulatory authorities.
3.2.1.
Criteria for Pausing or Stopping the Study
1. The following SAEs occurring within 1 month (28 days) of the JCAR017 infusion or the 
start of the combination agent whichever occurs last, will be a criterion for pausing or 
stopping the study or arm if not related to disease progression considering SRC/ DSMB 
recommendation:

Life-threatening (Grade 4) toxicity attributable to protocol therapy that is unexpected, 
unmanageable (ie, does not resolve to Grade 3 or lower within 7 days), and unrelated 
to chemotherapy

Life threatening (Grade 4) toxicity to vital organs in 2 or more subjects

Death 
2. If any of the following occur, the study or a specific arm will be terminated:
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
Any subject develops uncontrolled JCAR017 proliferation that is unresponsive to 
treatment

Any subject develops detectable replication-competent lentivirus (RCL) during the 
study

The Sponsor, IRB/ IEC, or DSMB decides that subject safety may be compromised 
by continuing the study

The Sponsor decides to discontinue the development of JCAR017 and/or the 
combination agent in this indication or the development of JCAR017 and/or the 
combination agent for all indications
Medical monitor(s) will review the events in item 1 and 2 closely, and if any unusual signal is 
detected or a study treatment-related death occurs, the DSMB will be informed immediately. 
3.3.
Safety Monitoring Boundaries
During the Phase 2 portion of the study, besides items 1 and 2 in Section 3.2.1, Bayesian 
framework safety monitoring boundaries (Thall, 1994; Yao, 2013) will be used to help detect 
safety signals that may occur during the course of the study. The boundaries are based on the 
cumulative number of subjects who have received at least one dose of JCAR017 or one dose of 
the combination agent and who experienced either at least one event of the following grades 
within 1 month (28 days) of JCAR017 infusion or start of combination agent whichever occurs 
last:

A Grade 3 treatment-emergent adverse events of special interest (AESIs) that is 
unmanageable or fails to resolve to Grade 2 or better after 21 days

A Grade 4 treatment-emergent AESI that is unmanageable or fails to resolve to Grade 
3 or better after 7 days
Adverse events of special interest (AESI) may include but are not limited to:

Infusion related reaction

Cytokine release syndrome (CRS)

Neurological toxicity (NT)

Macrophage activation syndrome (MAS)

Tumor lysis syndrome (TLS)

Prolonged cytopenia

Hypogammaglobulinemia

Infections Grade ≥ 3

Autoimmune disorders

Secondary malignancy
Whenever the safety boundaries are crossed, enrollment will be paused and an ad hoc DSMB 
meeting will be held to review the data. The data to be reviewed by the DSMB are specified in 
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the DSMB charter and DSMB report template. The DSMB may override the safety stopping 
boundaries to recommend study continuation based on clinical and overall risk benefit 
considerations. Details regarding the Bayesian framework and the safety monitoring boundaries 
will be included in the statistical analysis plan.
The other safety monitoring activity includes periodic DSMB meetings as specified in the 
DSMB charter. 
3.4.
Study Duration for Subjects 
The duration of participation for subjects who complete the study will be approximately 26 
months. All subjects who receive JCAR017 will be eligible and asked to enroll into a separate 
LTFU protocol after completion of this study.
3.5.
End of Trial
The End of Trial is defined as either the date of the last visit of the last subject to complete the 
post-treatment follow-up, or the date when the last subject enters the LTFU study, or the date of 
receipt of the last data point from the last subject that is required for primary, secondary and/or 
exploratory analysis, as prespecified in the protocol, whichever is the later date.
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4.
STUDY POPULATION
4.1.
Number of Subjects 
Approximately 55 subjects with R/R aggressive B-cell NHL in each arm will be enrolled
worldwide to reach up to 18 DLT evaluable subjects in Phase 1 and if the expansion phase is 
opened at least 26 safety and efficacy evaluable subjects in Phase 2, in each arm. In study arms 
where Phase 1 subcohorts may evaluate both different combination doses and different treatment 
schedules the number of subjects treated may be higher (eg, a minimum of 6 and up to 36 
evaluable subjects for Arm C). 
4.2.
Inclusion Criteria
Subjects must satisfy the following criteria to be enrolled in the study:
1. Subject is ≥ 18 years of age at the time of signing the informed consent form (ICF). 
2. Subject must understand and voluntarily sign an ICF prior to any study-related 
assessments/procedures being conducted. 
3. Subject is willing and able to adhere to the study visit schedule and other protocol 
requirements.
4. Subject must have histologically confirmed at last relapse aggressive B-cell NHL 
according to the 2016 revision of the WHO classification of lymphoid neoplasms 
(Swerdlow, 2016) defined as:
a.
DLBCL NOS including transformed indolent NHL
b. Follicular lymphoma Grade 3B
c.
T cell/histiocyte-rich large B-cell lymphoma 
d. EBV positive DLBCL, NOS 
e.
Primary mediastinal (thymic) large B-cell lymphoma 
f.
High grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements 
with DLBCL histology (double/triple-hit lymphoma) 
Note: If archival material is not available from latest relapse, a new tumor biopsy is 
required.
5. Subject´s disease must have relapsed or be refractory to at least 2 prior lines of systemic 
therapy. Previous therapy must have included a CD20-targeted agent and an 
anthracycline.
Note: For subjects with transformed disease, the subject should have had at least 2 lines 
of systemic therapy for his/her transformed disease (ie, the DLBCL) to be eligible. Lines 
of therapy do not include those given for a previously indolent condition (eg, follicular 
lymphoma, CLL). Subjects do not have to have received anthracycline for their DLBCL 
if received for indolent disease.
6. Subject must have:
a.
Positron emission tomography (PET)-positive (Deauville score 4 or 5) and computed 
tomography (CT) measurable disease as per Lugano Classification (Cheson, 2014)
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b. Sum of product of perpendicular diameters (SPD) of up to 6 index lesions ≥ 25 cm2
by CT scan (not applicable to Arm A or B or subjects with Richter’s transformation)
7. ECOG performance status ≤ 1 at screening.
8. Adequate organ function, defined as:

Adequate bone marrow function to receive lymphodepleting chemotherapy defined 
as: absolute neutrophil count (ANC) ≥ 1.0 x 109 cells/L and platelets ≥ 50 x 109
cells/L

Creatinine clearance ≥ 60 mL/min (estimated creatinine clearance by Cockcroft Gault 
see Appendix I for calculation)

Serum alanine transaminase (ALT) ≤ 3.0 x ULN. In the case of documented liver 
involvement by lymphoma, ALT must be ≤ 5.0 x ULN

Serum total bilirubin ≤ 2.0 mg/dL (34 μmol/L). In the case of Gilbert’s syndrome, or 
documented liver or pancreatic involvement by lymphoma, serum total bilirubin must 
be ≤ 3.0 mg/dL (51 μmol/L)

Adequate pulmonary function, defined as ≤ Grade 1 dyspnea according to Common 
Terminology Criteria for Adverse Events (CTCAE version 4.03) and oxygen 
saturation (SaO2) ≥92% on room air

Adequate cardiac function, defined as left ventricular ejection fraction (LVEF) ≥ 40% 
as assessed by echocardiogram (ECHO) or multi-gated acquisition scan (MUGA) 
performed within 4 weeks of leukapheresis

Troponin-T or I (TnT or TnI) value < ULN (Arms B and E) or brain natriuretic 
peptide (BNP) ≤ 300 pg/ml (Arm B). Note: Subjects with baseline troponin-T or I > 
ULN or BNP > 100 pg/mL are eligible but should have cardiologist evaluation prior 
to enrollment in the trial for baseline assessment and optimization of cardioprotective 
therapy after discussion with the sponsor’s medical monitor
Note: If troponin-T cannot be performed locally, troponin-I may be used instead. If BNP 
cannot be performed locally, NT pro-BNP may be used instead.
9. Subjects must agree to not donate blood, organs, sperm or semen, and egg cells for usage 
in other individuals while receiving the combination agent and for at least 12 months 
following lymphodepleting chemotherapy, or 5 months after the last dose of nivolumab 
or relatlimab, whichever is later. There is insufficient exposure data to provide any 
recommendation concerning the duration of refraining from tissue donation following 
treatment with JCAR017. Therefore, subjects treated with JCAR017 should not donate 
blood, organs, tissues or cells for transplantation. 
10. Females of childbearing potential (FCBP) must:
a.
Have 2 or 3 negative pregnancy tests as verified by the Investigator (one negative 
serum beta-human chorionic gonadotropin [ß-hCG] pregnancy test result at screening, 
one prior to Day 1 combination for subjects receiving the combination agent pre-
JCAR017 infusion and one within 7 days prior to the first dose of lymphodepleting 
chemotherapy). She must agree to ongoing pregnancy testing during the course of the 
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study, and after end of study treatment, and for Arms B, C and F as specified in the 
CC-122, CC-220 or CC-99282 Pregnancy Prevention and Risk Management Plan 
(PPRMP) (see Appendix N, Appendix O, Appendix Q). This applies even if the 
subject practices true abstinence* from heterosexual contact.
b. Either commit to true abstinence* from heterosexual contact (which must be 
reviewed on a monthly basis and source documented) or agree to use, and be able to 
comply with, effective contraception without interruption. Contraception methods 
must include 1 highly effective and 1 additional effective (barrier) method of 
contraception, from screening until at least 12 months after lymphodepleting 
chemotherapy or 3 months after the last dose of durvalumab (Arm A), or 28 days 
after the last dose of CC-122 (Arm B), CC-220 (Arm C) or CC-99282 (Arm F) as 
specified in the CC-122, CC-220 and CC-99282 PPRMP (see Appendix N,
Appendix O, Appendix Q), or 28 days after the last dose of ibrutinib (Arm D), or 24 
weeks after the last dose of nivolumab or relatlimab and as described in Appendix P
(Arm E), whichever is later. There is insufficient exposure data to provide any 
recommendation concerning the duration of contraception following treatment with 
JCAR017. Any decision regarding contraception after JCAR017 infusion should be 
discussed with the treating physician.
c.
Agree to abstain from breastfeeding during study participation and for at least 1 year
after lymphodepleting chemotherapy or 3 months after the last dose of durvalumab 
(Arm A) or 28 days after the last dose of CC-122 (Arm B), CC-220 (Arm C), 
ibrutinib (Arm D), or CC-99282 (Arm F). There is insufficient exposure data to 
provide any recommendation concerning the duration of abstaining from 
breastfeeding following treatment with JCAR017. Any decision regarding 
breastfeeding after JCAR017 infusion should be discussed with the treating 
physician.
d. Agree to ongoing pregnancy testing during the course of the study as outlined in the 
CC-122 PPRMP (Arm B) CC-220 PPRMP (Arm C) or CC-99282 PPRMP (Arm F).
Note: Highly effective methods are defined as those that result in a low failure rate (ie, less 
than 1% per year) when used consistently and correctly. The following are examples of 
highly effective and additional effective methods of contraception:
Highly effective methods of contraception:

Intrauterine device (IUD)

Hormonal (birth control pill, injections, implants)

Tubal ligation 

Partner’s vasectomy 
Additional effective methods of contraception:

Male condom 

Diaphragm 

Cervical cap 
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11. Male subjects must:

Practice true abstinence* (which must be reviewed on a monthly basis) or agree to 
use a condom during sexual contact with a pregnant female or a female of 
childbearing potential while participating in the study, during dose interruptions, and 
for 12 months after lymphodepleting chemotherapy or for at least 3 months (33 weeks 
for Arm E) after the last dose of the combination agent even if he has undergone a 
successful vasectomy, whichever occurs last. 
There is insufficient exposure data to provide any recommendation concerning the 
duration of contraception following treatment with JCAR017. Any decision regarding 
contraception after JCAR017 infusion should be discussed with the treating physician.
* True abstinence is acceptable when this is in line with the preferred and usual lifestyle 
of the subject. In contrast, periodic abstinence (eg, calendar, ovulation, symptothermal, 
post-ovulation methods) and withdrawal are not acceptable methods of contraception.
4.3.
Exclusion Criteria
The presence of any of the following will exclude a subject from enrollment:
1. Subject has any significant medical condition, laboratory abnormality, or psychiatric 
illness that would prevent the subject from participating in the study based on 
investigator´s judgment.
2. Subject has any condition including the presence of laboratory abnormalities, which 
places the subject at unacceptable risk if he/she were to participate in the study based on 
investigator´s judgment.
3. Subject has any condition that confounds the ability to interpret data from the study based 
on investigator´s judgment.
4. Subjects with prior history of malignancies, other than aggressive R/R NHL, unless the 
subject has been free of the disease for ≥ 2 years with the exception of the following non-
invasive malignancies:

Basal cell carcinoma of the skin

Squamous cell carcinoma of the skin

Carcinoma in situ of the cervix

Carcinoma in situ of the breast

Incidental histologic finding of prostate cancer (T1a or T1b using the TNM [tumor, 
nodes, metastasis] clinical staging system) or curatively treated prostate cancer 

Other completely resected stage 1 solid tumor with low risk for recurrence
5. Prior treatment with any gene therapy product, including gene therapy with a non-
integrating vector.
6. Prior treatment with any adoptive T cell therapy; prior hematopoietic stem cell transplant 
(HSCT) is allowed.
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7. Prior allogeneic HSCT (Arm E); allogeneic HSCT within 90 days of leukapheresis (all 
other Arms).
8. Prior treatment with the combination agent from the assigned arm:
a.
Anti PD-1 or PD-L1 (Arms A and E)
b. CC-122 (Arm B) 
c.
CC-220 (Arm C)
d. Prior treatment with ibrutinib is not exclusionary for subjects on any study arm 
e.
Anti LAG-3 targeted agent (Arm E)
f.
CC-99282 (Arm F)
9. Removed
10. Presence of acute or chronic graft-versus-host disease (GVHD).
11. History of or active hepatitis B or hepatitis C or human immunodeficiency virus (HIV) 
infection.
12. Uncontrolled bacterial, viral or fungal infection at the time of leukapheresis, 
lymphodepleting chemotherapy or JCAR017 infusion.
13. Any history of myocarditis (Arm E); history any one of the following cardiovascular 
conditions within the past 6 months of signing the ICF: Class III or IV heart failure as 
defined by the New York Heart Association (NYHA), cardiac angioplasty or stenting, 
myocardial infarction, unstable angina, or other clinically significant cardiac disease (all 
Arms)
14. History or presence of clinically relevant central nervous system (CNS) pathology such 
as epilepsy, seizure, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, 
cerebellar disease, organic brain syndrome, or psychosis.
15. Subjects with active CNS or cerebrospinal fluid (CSF) involvement by malignancy.
16. Pregnant or nursing (lactating) women.
17. Subjects with active autoimmune disorders/processes or active neurological or 
inflammatory disorders, including pneumonitis.
18. Treatment with alemtuzumab within 6 months of leukapheresis, or treatment with 
fludarabine or cladribine within 3 months of leukapheresis.
19. Use of the following (see Section 8.2 for full details):

Therapeutic doses of corticosteroids (defined as > 20 mg/day prednisone or 
equivalent) within 7 days of leukapheresis or 72 hours prior to JCAR017 
administration. Physiologic replacement, topical, inhaled, and intranasal steroids are 
permitted 

Chemotherapy given after leukapheresis to maintain disease control must be stopped 
≥ 7 days prior to lymphodepleting chemotherapy

Cytotoxic chemotherapeutic agents that are not considered lymphotoxic (see below) 
within 1 week of leukapheresis. Oral chemotherapeutic agents are allowed if at least 3 
half-lives have elapsed prior to leukapheresis 
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
Lymphotoxic chemotherapeutic agents (eg, cyclophosphamide, ifosfamide, 
bendamustine) within 2 weeks of leukapheresis 

Experimental agents within 4 weeks of leukapheresis unless no response or disease 
progression is documented on the experimental therapy and at least 3 half-lives have 
elapsed prior to leukapheresis 

GVHD therapies within 4 weeks of leukapheresis and JCAR017 administration (eg, 
calcineurin inhibitors, methotrexate or other chemotherapeutics, mycophenolate, 
rapamycin, thalidomide, immunosuppressive antibodies such as anti-tumor necrosis 
factor (anti-tumor necrosis factor [TNF]), anti-IL6, or anti-IL6R) 

Donor lymphocyte infusions (DLI) within 6 weeks of JCAR017 administration 

Radiation within 6 weeks of leukapheresis. Subjects must have progressive disease in 
irradiated lesions or have additional non-irradiated, Positron emission tomography 
(PET)-positive lesions to be eligible. Radiation to a single lesion, if additional non-
irradiated PET-positive lesions are present, is allowed up to 2 weeks prior to 
leukapheresis

Live attenuated vaccines within 90 days prior to leukapheresis
20. For subjects to receive oral combination therapy (Arms B, C, D or F): History of a 
gastrointestinal (GI) condition or procedure that in the opinion of the investigator may 
affect oral drug absorption.
21. Progressive tumor invasion of venous or arterial vessels.
22. Deep venous thrombosis (DVT)/pulmonary embolism (PE) not managed on a stable 
regimen of anticoagulation.
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5.
TABLES OF EVENTS
5.1.
Arm A
Table 10:
Table of Events, Arm A Cohort 1
Please refer to the specified protocol section for further details on each procedure.
Protocol 
Section
Pre-Treatment Period
Treatment Period
Post-Treatment Period
Survi-
val 
fol-
low-
up
Screen-
ing
Leuka-
pheresis
Pre-
lympho-
depletion 
evaluation
Lympho-
depletion 
(start)
Follow-up perioda
Study Day
N/A
-42 to -
28
-42 to -
28
-14 to-7
-10 to-5
1
2
3
4
8
11
15
22b
29b
36b, 
43, 
57
85c 180 270
365
545
730 
EOS
q3m
Study Month
1
3
6
9
12
18
24
Visit Window (days)
+1
±1
±1
±2
±2
±7
±2
±7
±14 ±14
±30
±30
±30
±30
Procedures
Obtain consent
6.1.1
xd
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
I/E criteria 
4.2, 4.3
6.1.2  
6.2.1
x
x
x
x
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
Medical history
6.1.1
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
IPI 
6.1.1
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
ECOG 
6.4.7
x
xe
-
x
x
-
-
-
x
-
x
x
x
xf
x
x
x
x
x
x
-
Height
6.4.4
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
Weight
6.4.4
x
-
x
-
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
Physical examination
6.4.1
xg
-
x
-
x
x
x
x
x
x
x
x
x
xf
x
x
x
x
x
x
-
Routine neurologic 
examination
6.4.5
x
-
x
-
x
x
x
x
x
x
x
x
x
x
x
-
-
-
-
-
-
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Table 10:
Table of Events, Arm A Cohort 1 (Continued)
Protocol 
Section
Pre-Treatment Period
Treatment Period
Post-Treatment Period
Survi
-val 
fol-
low-
up
Screen-
ing
Leuka-
pheresis
Pre-
lympho-
depletion 
evaluation
Lymho-
depletion 
(start)
Follow-up perioda
Study Day
N/A
-42 to -
28
-42 to -
28
-14 to-7
-10 to-5
1
2
3
4
8
11
15
22b
29b
36b, 
43, 
57
85c 180 270
365
545
730 
EOS
q3m
Study Month
1
3
6
9
12
18
24
Visit Window 
(days)
+1
±1
±1
±2
±2
±7
±2
±7 ±14 ±14
±30 ±30
±30
±30
MMSE
6.4.5
-
-
-
-
x
-
-
x
x
-
x
-
x
x
x
-
-
-
-
-
-
Vital signs
6.4.2
x
xe
x
x
x
x
x
x
x
x
x
x
xh
xf,h
xh
x
x
x
x
x
-
Pulse oximetry
6.4.3
x
-
x
x
x
x
x
x
x
x
x
x
x
xf
-
-
-
-
-
-
-
12-lead ECG 
6.4.9
x
-
xi
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
MUGA/ECHO 
6.4.8
xj
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
Viral serology 
6.1.1
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
Serum pregnancy 
6.1
x
-
-
xk
-
-
-
-
-
-
-
-
-
-
x
x
-
-
-
-
-
Urinalysis
6.1
x
-
-
-
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
CSF assessment
6.4.6
6.7.2
xl
-
-
-
if clinically indicated
-
Creatinine clearance
6.1
x
-
-
xk
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
Hematology 
6.4.12
x
xe
x
x
x
x
x
x
x
x
x
x
x
xf
x
x
x
x
x
x
-
Coagulation
6.4.12
x
-
x
-
x
x
x
x
x
x
x
x
x
xf
-
-
-
-
-
-
-
Chemistry
6.4.12
x
xe
x
x
x
x
x
x
x
x
x
x
x
xf
x
x
x
x
x
x
-
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Table 10:
Table of Events, Arm A Cohort 1 (Continued)
Protocol 
Section
Pre-Treatment Period
Treatment Period
Post-Treatment Period
Survi-
val 
fol-
low-
up
Screen-
ing
Leuka-
pheresis
Pre-
lympho-
depletion 
evaluation
Lymho-
depletion 
(start)
Follow-up perioda
Study Day
N/A
-42 to -
28
-42 to -
28
-14 to-7
-10 to-5
1
2
3
4
8
11
15
22b
29b
36b, 
43, 
57
85c 180 270
365
545
730 
EOS
q3m
Study Month
1
3
6
9
12
18
24
Visit Window 
(days)
+1
±1
±1
±2
±2
±7
±2
±7
±14 ±14
±30 ±30
±30
±30
Inflammatory 
markers 
6.4.12
x
-
x
-
x
x
x
x
x
x
x
x
x
x
-
-
-
-
-
-
-
Immunoglobulins
6.4.12
x
-
-
-
-
-
-
-
-
-
x
x
x
x
xm
xm
xm
xm
xm
xm
-
Thyroid function 
tests 
6.4.12
x
-
-
-
x
-
-
-
-
-
x
-
x
x
x
x
x
x
x
x
-
HLA typing (only 
for subjects with 
prior allogeneic 
HSCT)
6.1.1
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
Donor chimerism 
(only for subjects 
with prior allogeneic 
HSCT)
6.1.1
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
Leukapheresis 
6.1.2
-
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
Lymphodepleting 
chemotherapy 
7.2.1
-
-
-
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
JCAR017 
administration 
7.2.2
-
-
-
-
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
Approved
1.0
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Table 10:
Table of Events, Arm A Cohort 1 (Continued)
Protocol 
Section
Pre-Treatment Period
Treatment Period
Post-Treatment Period
Survi
-val 
fol-
low-
up
Screen-
ing
Leuka-
pheresis
Pre-
lympho-
depletion 
evaluation
Lymho-
depletion 
(start)
Follow-up perioda
Study Day
N/A
-42 to -
28
-42 to -
28
-14 to-7
-10 to-5
1
2
3
4
8
11
15
22b
29b
36b, 
43, 
57
85c 180 270
365
545
730 
EOS
q3m
Study Month
1
3
6
9
12
18
24
Visit Window 
(days)
+1
±1
±1
±2
±2
±7
±2
±7 ±14 ±14
±30
±30
±30
±30
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1.0
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Table 10:
Table of Events, Arm A Cohort 1 (Continued)
Protocol 
Section
Pre-Treatment Period
Treatment Period
Post-Treatment Period
Survi-
val 
fol-
low-
up
Screen-
ing
Leuka-
pheresis
Pre-
lympho-
depletion 
evaluation
Lymho-
depletion 
(start)
Follow-up perioda
Study Day
N/A
-42 to -
28
-42 to -28
-14 to-7
-10 to-5
1
2
3
4
8
11
15
22b
29b
36b, 
43, 
57
85c 180 270
365
545
730 
EOS
q3m
Study Month
1
3
6
9
12
18
24
Visit Window (days)
+1
±1
±1
±2
±2
±7
±2
±7
±14 ±14
±30 ±30
±30
±30
Abbreviations: AE = adverse event; BMA = bone marrow aspirate; BMB = bone marrow biopsy; BNP = brain natriuretic peptide; 
; CNS = central nervous 
system; Con = concomitant; Con meds = concomitant medications; CR = complete response; CRS = cytokine release syndrome; CSF = cerebrospinal fluid; CT = computed 
tomography; D = day; diff = differential; ECG = electrocardiogram; ECHO = echocardiogram; ECOG = Eastern Cooperative Oncology Group; EORTC-QLQ-C30 = European 
Organisation for Research and Treatment of Cancer – Quality of Life C30 questionnaire; EOS = end of study; EQ-5D-5L = European Quality of Life-5 Dimensions health state 
classifier to 5 Levels; FU = follow-up; HLA = human leukocyte antigen; HSCT = hematopoietic stem cell transplant; I/E = inclusion and exclusion; IPI = international prognostic 
index; IVIG = intravenous immunoglobulins; LD = lymphodepleting; MMSE = Mini Mental State Examination; MRI= magnetic resonance imaging; MUGA = multi-gated 
Approved
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Table 11:
Table of Events, Arm A Cohort 1A-2
Protocol 
Section
Pre-Treatment Period
Treatment Period
Post-Treatment Period
Sur-
vival 
fol-
low-
up
Screening
Leuk-
apheresis
Pre-
lympho-
depletion 
evaluation
Lympho-
depletion 
(start)
Follow-up perioda
Study Day
N/A
-42 to -28
-42 to -28
-14 to-7
-10 to -5
1
2
3
4
8
11
15
22, 
36
29
43, 50, 
57, 71
85b
180
270
365
545
730 
(EOS) q3m
Study Month
1
3
6
9
12
18
24
Visit Window (days)
+1
± 1
± 1
± 2
± 2
± 7
± 2
± 7
± 14
± 14 ± 30 ± 30
± 30
± 30
Procedures
Obtain consent
6.1.1
xc
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
I/E criteria 
4.2, 4.3
6.1.2
6.2.1
x
x
x
x
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
Medical history
6.1.1
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
IPI 
6.1.1
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
ECOG
6.4.7
x
xd
-
x
x
-
-
-
x
-
x
x
x
x
x
x
x
x
x
x
-
Height
6.4.4
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
Weight
6.4.4
x
-
x
-
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
Physical examination
6.4.1
xe
-
x
-
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
-
Routine neurologic 
examination
6.4.5
x
-
x
-
x
x
x
x
x
x
x
x
x
x
x
-
-
-
-
-
-
MMSE 
6.4.5
-
-
-
-
x
-
-
x
x
-
x
-
x
x
x
-
-
-
-
-
-
Vital signs
6.4.2
x
xd
x
x
x
x
x
x
x
x
x
x
x
xf
xf
x
x
x
x
x
-
Pulse oximetry
6.4.3
x
-
x
x
x
x
x
x
x
x
x
x
x
x
-
-
-
-
-
-
-
12-lead ECG 
6.4.9
x
-
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
Approved
1.0
v

EDMS Doc. Number: 25256661 - 21712569
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Protocol JCAR017-BCM-002 Amendment 6 Final: 27 Jan 2021
Table 11:
Table of Events, Arm A Cohort 1A-2 (Continued)
Protocol 
Section
Pre-Treatment Period
Treatment Period
Post-Treatment Period
Sur-
vival 
fol-
low-
up
Screening
Leuk-
apheresis
Pre-
lympho-
depletion 
evaluation
Lympho-
depletion 
(start)
Follow-up perioda
Study Day
N/A
-42 to -28
-42 to -28
-14 to-7
-10 to -5
1
2
3
4
8
11
15
22, 
36
29
43, 50, 
57, 71
85b
180
270
365
545
730 
(EOS) q3m
Study Month
1
3
6
9
12
18
24
Visit Window (days)
+1
± 1
± 1
± 2
± 2
± 7
± 2
± 7
± 14
± 14 ± 30 ± 30
± 30
± 30
MUGA/ECHO 
6.4.8
xg
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
Viral serology 
6.1.1
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
Serum pregnancy 
6.1
x
-
-
xh
-
-
-
-
-
-
-
-
-
-
x
x
-
-
-
-
-
Urinalysis
6.1
x
-
-
-
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
CSF assessment
6.4.6
6.7.2
xi
-
-
-
if clinically indicated
-
Creatinine clearance
6.1
x
-
-
xh
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
Hematology 
6.4.12
x
xd
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
-
Coagulation
6.4.12
x
-
x
-
x
x
x
x
x
x
x
x
x
x
-
-
-
-
-
-
-
Chemistry
6.4.12
x
xd
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
-
Inflammatory markers 
6.4.12
x
-
x
-
x
x
x
x
x
x
x
x
x
x
-
-
-
-
-
-
-
Immunoglobulins
6.4.12
x
-
-
-
-
-
-
-
-
-
x
x
x
x
xj
xj
xj
xj
xj
xj
-
Thyroid function tests
6.4.12
x
-
-
-
x
-
-
-
-
-
-
-
-
x
x
x
x
x
x
x
-
HLA typing (only for 
subjects with prior 
allogeneic HSCT)
6.1.1
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
Approved
1.0
v

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Table 11:
Table of Events, Arm A Cohort 1A-2 (Continued)
Protocol 
Section
Pre-Treatment Period
Treatment Period
Post-Treatment Period
Sur-
vival 
fol-
low-
up
Screening
Leuk-
apheresis
Pre-
lympho-
depletion 
evaluation
Lympho-
depletion 
(start)
Follow-up perioda
Study Day
N/A
-42 to -28
-42 to -28
-14 to-7
-10 to -5
1
2
3
4
8
11
15
22, 
36
29
43, 50, 
57, 71
85b
180
270
365
545
730 
(EOS) q3m
Study Month
1
3
6
9
12
18
24
Visit Window (days)
+1
± 1
± 1
± 2
± 2
± 7
± 2
± 7
± 14
± 14 ± 30 ± 30
± 30
± 30
Donor chimerism (only 
for subjects with prior 
allogeneic HSCT)
6.1.1
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
Leukapheresis 
6.1.2
-
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
Lymphodepleting 
chemotherapy 
7.2.1
-
-
-
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
JCAR017 administration 7.2.2.1
-
-
-
-
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
Durvalumab administration (Arm A)
Cohort 1A-2
6.2.6
7.1.2
-
x see Table 3
for dosing 
schedule 
details
-
AEs/Con meds/ Con 
procedures
8
10
AEs, con meds and con 
procedures related to protocol 
mandated procedures
All AEs, con meds and con procedurest
AEs related to JCAR017 and 
/or combination agents, 
associated con meds and con 
procedures
-
PET-CT/ MRI
6.5
x
-
xk
-
-
-
-
-
-
-
-
-
x
-
x
xl
xl
xl
xl
xl
-
BMB/BMA 
6.1
xm
-
-
-
-
-
-
-
-
-
-
-
xn
if clinically indicated
-
Tumor biopsy
6.1
xo
-
xk,o
-
-
-
-
-
-
-
-
-
xo
at progressiono, p
-
EORTC-QLQ-C30
6.8
-
-
x
-
x
-
-
-
-
-
-
-
x
x D57
x
x
x
x
x
x
-
EQ-5D-5L
6.8
-
-
x
-
x
-
-
-
-
-
-
-
x
x D57
x
x
x
x
x
x
-
Approved
1.0
v

Approved
1.0
v

Approved
1.0
v

Approved
1.0
v

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5.2.
Arm B
Table 12:
Table of Events, Arm B Cohort 1
Protocol 
Section
Pre-treatment Period
Treatment Period
Post-Treatment Period
Sur-
vival 
Fol-
low-
Up
Screen-
ing
Leuka-
pheresis
Pre-
lympho-
depletion 
Evaluation
LD 
chemo 
(start)
Follow-Up Perioda
Study Day
N/A
-42 
to -28
-42
to -28
-14 to -7
-10
to -5
1
2
3
4
8
11 15 22b
29b
30, 
31, 
32, 
39
36b, 
43, 
57
50, 
64, 
71, 
78
85
113
141,
169
180c 208
270
365
545
730 
EOS
q3m
Study Month
1
3
4
5
6
7
9
12
18
24
Visit Window 
(days)
+1 ±1 ±1 ±2 ±2
±7
±2
±2
±7
±7
±7
±7
±14
±14
±30
±30
±30
±30
Procedures
Obtain consent
6.1.1
xd
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
I/E criteria 
4.2, 4.3
6.1.2  
6.2.1
x
x
x
x
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
Medical history
6.1.1
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
IPI 
6.1.1
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
ECOG 
6.4.7
x
xe
-
x
x
-
-
-
x
-
x
x
x
-
x
x
x
x
x 
D141
x
x
x
x
x
x
-
Height
6.4.4
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
Weight
6.4.4
x
-
x
-
x
-
-
-
-
-
-
-
x
-
x 
D57
-
x
x
x 
D141
x
x
-
-
-
-
-
Physical 
examination
6.4.1
xf
-
x
-
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x 
D141
x
x
x
x
x
x
-
Routine neurologic 
examination
6.4.5
x
-
x
-
x
x
x
x
x
x
x
x
x
x
x
-
x
-
-
-
-
-
-
-
-
-
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Table 12:
Table of Events, Arm B Cohort 1 (Continued)
Protocol 
Section
Pre-treatment Period
Treatment Period
Post-Treatment Period
Sur-
vival 
Fol-
low-
Up
Screen-
ing
Leuka-
pheresis
Pre-
lympho-
depletion 
Evaluation
LD 
chemo 
(start)
Follow-Up Perioda
Study Day
N/A
-42 
to -28
-42
to -28
-14 to -7
-10
to -5
1
2
3
4
8
11 15 22b
29b
30, 
31, 
32, 
39
36b, 
43, 
57
50, 
64, 
71, 
78
85
113
141,
169
180c 208
270
365
545
730 
EOS
q3m
Study Month
1
3
4
5
6
7
9
12
18
24
Visit Window 
(days)
+1 ±1 ±1 ±2 ±2
±7
±2
±2
±7
±7
±7
±7
±14
±14
±30
±30
±30
±30
MMSE
6.4.5
-
-
-
-
x
-
-
x
x
-
x
-
x
x 
D32
x
-
x
-
-
-
-
-
-
-
-
-
Vital signs
6.4.2
x
xe
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
-
Pulse oximetry
6.4.3
x
-
x
x
x
x
x
x
x
x
x
x
x
x
x
x
-
-
-
-
-
-
-
-
-
-
12-lead ECG 
6.4.9
x
-
xg
-
-
-
-
-
-
-
-
-
x
If clinically indicated
-
MUGA/ECHO
6.4.8
xh
-
-
-
-
-
-
-
-
-
-
-
-
If clinically indicated
-
Troponin-T and 
BNP
6.1
x
-
-
-
-
-
-
-
-
-
-
-
x
If clinically indicated
-
Viral serology 
6.1.1
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
Pregnancy testing
6.1
x
-
-
xi
-
-
-
-
-
-
-
xj
xj
-
x
x 
D50
x
x
x
-
xk, l
-
-
-
-
-
Pregnancy 
prevention 
counselling
6.1
x
-
-
-
-
-
-
-
-
-
-
-
x
-
x 
D43, 
D57
-
x
x
x
-
xk, l
-
-
-
-
-
Urinalysis
6.1
x
-
-
-
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
CSF assessment
6.4.6
6.7.2
xm
-
-
-
if clinically indicated
-
Creatinine 
clearance
6.1
x
-
-
xi
-
-
-
-
-
-
-
-
x
-
-
-
-
-
-
-
-
-
-
-
-
-
Approved
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JCAR017
Protocol JCAR017-BCM-002
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Confidential and Proprietary
95
Protocol JCAR017-BCM-002 Amendment 6 Final: 27 Jan 2021
Table 12:
Table of Events, Arm B Cohort 1 (Continued)
Protocol 
Section
Pre-treatment Period
Treatment Period
Post-Treatment Period
Sur-
vival 
Fol-
low-
Up
Screen-
ing
Leuka-
pheresis
Pre-
lympho-
depletion 
Evaluation
LD 
chemo 
(start)
Follow-Up Perioda
Study Day
N/A
-42 
to -28
-42
to -28
-14 to -7
-10
to -5
1
2
3
4
8
11 15 22b
29b
30, 
31, 
32, 
39
36b, 
43, 
57
50, 
64, 
71, 
78
85
113
141,
169
180c 208
270
365
545
730 
EOS
q3m
Study Month
1
3
4
5
6
7
9
12
18
24
Visit Window 
(days)
+1 ±1 ±1 ±2
±2
±7
±2
±2
±7
±7
±7
±7
±14
±14
±30
±30
±30
±30
Hematology
6.4.12
x
xe
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
-
Coagulation
6.4.12
x
-
x
-
x
x
x
x
x
x
x
x
x
x
x
-
-
-
-
-
-
-
-
-
-
-
Chemistry
6.4.12
x
xe
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
-
Inflammatory 
markers 
6.4.12
x
-
x
-
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
-
-
-
-
-
Immunoglobulins
6.4.12
x
-
-
-
-
-
-
-
-
-
x
x
x
-
x
D57
-
xn
-
-
xn
-
xn
xn
xn
xn
-
HLA typing (only 
for subjects with 
prior allogeneic 
HSCT)
6.1.1
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
Donor chimerism 
(only for subjects 
with prior 
allogeneic HSCT)
6.1.1
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
Leukapheresis 
6.1.2
-
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
Lymphodepleting 
chemotherapy 
7.2.1
-
-
-
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
JCAR017 
administration
7.2.2
-
-
-
-
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
Approved
1.0
v

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Protocol JCAR017-BCM-002
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Confidential and Proprietary
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Protocol JCAR017-BCM-002 Amendment 6 Final: 27 Jan 2021
Table 12:
Table of Events, Arm B Cohort 1 (Continued)
Protocol 
Section
Pre-treatment Period
Treatment Period
Post-Treatment Period
Sur-
vival 
Fol-
low-
Up
Screen-
ing
Leuka-
pheresis
Pre-
lympho-
depletion 
Evaluation
LD 
chemo 
(start)
Follow-Up Perioda
Study Day
N/A
-42 
to -28
-42
to -28
-14 to -7
-10
to -5
1
2
3
4
8
11 15 22b
29b
30, 
31, 
32, 
39
36b, 
43, 
57
50, 
64, 
71, 
78
85
113
141,
169
180c 208
270
365
545
730 
EOS
q3m
Study Month
1
3
4
5
6
7
9
12
18
24
Visit Window 
(days)
+1 ±1 ±1 ±2 ±2
±7
±2
±2
±7
±7
±7
±7
±14
±14
±30
±30
±30
±30
CC-122 administration 
Cohort 1
3.1.4
7.2.5
-
x see Table 4 for dosing schedule details
Subjects to enter doses taken in diary
-
VTE prophylaxis
10.6.4.6
-
x
if needed
-
PET-CT/ MRI
6.5
x
-
xg
-
-
-
-
-
-
-
-
-
x
-
-
-
x
-
-
xo
-
xo
xo
xo
xo
-
BMB/BMA 
6.1
xp
-
-
-
-
-
-
-
-
-
-
-
xq
if clinically indicated
-
Tumor biopsy
6.1
xr
-
xg r
-
-
-
-
-
-
-
-
-
xr
at progressionr,s
-
AEs/ Con meds/ 
Con procedures
8
10
AEs, con meds and con 
procedures related to protocol 
mandated procedures
All AEs, con meds and con procedurest
AEs related to JCAR017 
and/or combination agents, 
associated con meds and con 
procedures
-
EORTC-QLQ-C30
6.8
-
-
x
-
x
-
-
-
-
-
-
-
x
-
x 
D57
-
x
-
-
x
-
x
x
x
x
-
EQ-5D-5L
6.8
-
-
x
-
x
-
-
-
-
-
-
-
x
-
x 
D57
-
x
-
-
x
-
x
x
x
x
-
Approved
1.0
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EDMS Doc. Number: 25256661 - 21712569
JCAR017
Protocol JCAR017-BCM-002
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Confidential and Proprietary
98
Protocol JCAR017-BCM-002 Amendment 6 Final: 27 Jan 2021
Table 12:
Table of Events, Arm B Cohort 1 (Continued)
Protocol 
Section
Pre-treatment Period
Treatment Period
Post-Treatment Period
Sur-
vival 
Fol-
low-
Up
Screen-
ing
Leuka-
pheresis
Pre-
lympho-
depletion 
Evaluation
LD 
chemo 
(start)
Follow-Up Perioda
Study Day
N/A
-42 
to -28
-42
to -28
-14 to -7
-10
to -5
1
2
3
4
8
11 15 22b
29b
30, 
31, 
32, 
39
36b, 
43, 
57
50, 
64, 
71, 
78
85
113
141,
169
180c 208
270
365
545
730 
EOS
q3m
Study Month
1
3
4
5
6
7
9
12
18
24
Visit Window 
(days)
+1 ±1 ±1 ±2 ±2
±7
±2
±2
±7
±7
±7
±7
±14
±14
±30
±30
±30
±30
Abbreviations: AE = adverse event; BMA = bone marrow aspirate; BMB = bone marrow biopsy; BNP = brain natriuretic peptide;
; CNS = central nervous 
system; Con = concomitant; Con meds = concomitant medications; CR = complete response; CRS = cytokine release syndrome; CSF = cerebrospinal fluid; CT = computed 
tomography; D = day; ECG = electrocardiogram; ECHO = echocardiogram; ECOG = Eastern Cooperative Oncology Group; EORTC-QLQ-C30 = European Organisation for 
Research and Treatment of Cancer – Quality of Life C30 questionnaire; EOS = end of study; EQ-5D-5L = European Quality of Life-5 Dimensions health state classifier to 5 
Levels; HLA = human leukocyte antigen; HSCT = hematopoietic stem cell transplant; I/E = inclusion and exclusion; IPI = international prognostic index; IVIG = intravenous 
immunoglobulins; LD = lymphodepleting chemotherapy; MMSE = Mini Mental State Examination; MRI= magnetic resonance imaging; MUGA = multi-gated acquisition scan; 
Approved
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Confidential and Proprietary
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Protocol JCAR017-BCM-002 Amendment 6 Final: 27 Jan 2021
5.3.
Arm C
Table 13:
Table of Events, Arm C 
Please refer to the specified protocol section for further details on each procedure.
Protocol 
Section
Pre-JCAR017 period
JCAR017 treatment period
Post-Treatment Period
Survival 
Follow-
up
Screen-
ing
Leuka-
pheresi
s
Pre-
lympho-
depletion 
Evaluatio
n
LD 
chemo 
(start)
Follow-Up Perioda
Study Day
N/A
-42 
to -28
-42
to -28
-14 to -7
-10
to -5
1b
2
3
4
8b
11
15b
22
29
36c, 43c, 
57
85d
113e
180
270
365
545
730 
EOS
q3m
Study Month
1
3
4
6
9
12
18
24
Visit Window 
(days)
+1 ±1
±1
±2
±2
±7
±2
±7
±7
±7
±14
±30 ±30
±30
±30
Obtain consent
6.1.1
xf
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
I/E criteria 
4.2, 4.3
6.1.2  
6.2.1
x
x
x
x
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
IRT registration
7.3
x
x
x
x
x
-
-
-
x
B
-
x
A
-
x
x 
D57
x
-
x
-
-
-
x
-
Medical history
6.1.1
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
IPI 
6.1.1
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
ECOG 
6.4.7
x
xg
-
x
x
-
-
-
x
-
x
x
x
x
x
x
x
x
x
x
x
-
Height
6.4.4
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
Weight
6.4.4
x
-
x
-
x
-
-
-
-
-
-
-
x
x 
D57
x
x
-
-
-
-
-
-
Physical 
examination
6.4.1
xh
-
x
-
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
-
Routine 
neurologic 
examination
6.4.5
x
-
x
-
x
x
x
x
x
x
x
x
x
x
x
-
-
-
-
-
-
-
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Table 13:
Table of Events, Arm C (Continued)
Protocol 
Section
Pre-JCAR017 period
JCAR017 treatment period
Post-Treatment Period
Survival 
Follow-
up
Screen-
ing
Leuka-
pheresi
s
Pre-
lympho-
depletion 
Evaluatio
n
LD 
chemo 
(start)
Follow-Up Perioda
Study Day
N/A
-42 
to -28
-42
to -28
-14 to -7
-10
to -5
1b
2
3
4
8b
11
15b
22
29
36c, 43c, 
57
85d
113e
180
270
365
545
730 
EOS
q3m
Study Month
1
3
4
6
9
12
18
24
Visit Window 
(days)
+1 ±1
±1
±2
±2
±7
±2
±7
±7
±7
±14
±30 ±30
±30
±30
MMSEi
6.4.5
-
-
-
-
x
-
-
x
x
-
x
-
x
x
x
-
-
-
-
-
-
-
Vital signs
6.4.2
x
xg
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
-
Pulse oximetry
6.4.3
x
-
x
x
x
x
x
x
x
x
x
x
x
x 
-
-
-
-
-
-
-
-
12-lead ECG 
6.4.9
x
-
xj
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
MUGA/ECHO
6.4.8
xk
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
Viral serology 
6.1.1
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
Pregnancy testing
6.1
x
-
-
xl,m
x 
B,C
x 
A
-
-
xm
B,C
-
xm
xm
xm
x
D36 
(A,B), 
D43 (A), 
D57
xn,o
xn,o
xo
xo
xo
-
-
-
Pregnancy 
prevention 
counselling
6.1
x
-
-
x
x
C
-
-
-
x
B
-
x 
A
-
x
x 
D57
xn,o
xn,o
-
-
-
-
-
-
Urinalysis
6.1
x
-
-
-
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
CSF assessment
6.4.6
6.7.2
xp
-
-
-
if clinically indicated
-
Creatinine 
clearance
6.1
x
-
-
xl
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
Hematology
6.4.12
x
xg
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
-
Coagulation
6.4.12
x
-
x
-
x
x
x
x
x
x
x
x
x
x
-
-
-
-
-
-
-
-
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Table 13:
Table of Events, Arm C (Continued)
Protocol 
Section
Pre-JCAR017 period
JCAR017 treatment period
Post-Treatment Period
Survival 
Follow-
up
Screen-
ing
Leuka-
pheresi
s
Pre-
lympho-
depletion 
Evaluatio
n
LD 
chemo 
(start)
Follow-Up Perioda
Study Day
N/A
-42 
to -28
-42
to -28
-14 to -7
-10
to -5
1b
2
3
4
8b
11
15b
22
29
36c, 43c, 
57
85d
113e
180
270
365
545
730 
EOS
q3m
Study Month
1
3
4
6
9
12
18
24
Visit Window 
(days)
+1 ±1
±1
±2
±2
±7
±2
±7
±7
±7
±14
±30 ±30
±30
±30
Chemistry
6.4.12
x
xg
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
-
Inflammatory 
markers 
6.4.12
x
-
x
-
x
x
x
x
x
x
x
x
x
x
x
-
-
-
-
-
-
-
Immunoglobulins
6.4.12
x
-
-
-
-
-
-
-
-
-
x
x
x
x
D57
xq
-
xq
xq
xq
xq
xq
-
HLA typing (only 
for subjects with 
prior allogeneic 
HSCT)
6.1.1
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
Donor chimerism 
(only for subjects 
with prior 
allogeneic HSCT)
6.1.1
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
Leukapheresis 
6.1.2  
-
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
Lymphodepleting 
chemotherapy 
7.2.1
-
-
-
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
JCAR017 
administration
7.2.2
-
-
-
-
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
CC-220 
administration
3.1.5
7.2.6  
-
see Table 5 for dosing schedule details
Subjects to enter doses taken in diary
-
-
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Table 13:
Table of Events, Arm C (Continued)
Protocol 
Section
Pre-JCAR017 period
JCAR017 treatment period
Post-Treatment Period
Survival 
Follow-
up
Screen-
ing
Leuka-
pheresi
s
Pre-
lympho-
depletion 
Evaluatio
n
LD 
chemo 
(start)
Follow-Up Perioda
Study Day
N/A
-42 
to -28
-42
to -28
-14 to -7
-10
to -5
1b
2
3
4
8b
11
15b
22
29
36c, 43c, 
57
85d
113e
180
270
365
545
730 
EOS
q3m
Study Month
1
3
4
6
9
12
18
24
Visit Window 
(days)
+1 ±1
±1
±2
±2
±7
±2
±7
±7
±7
±14
±30 ±30
±30
±30
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Table 13:
Table of Events, Arm C (Continued)
Protocol 
Section
Pre-JCAR017 period
JCAR017 treatment period
Post-Treatment Period
Survival 
Follow-
up
Screen-
ing
Leuka-
pheresi
s
Pre-
lympho-
depletion 
Evaluatio
n
LD 
chemo 
(start)
Follow-Up Perioda
Study Day
N/A
-42 
to -28
-42
to -28
-14 to -7
-10
to -5
1b
2
3
4
8b
11
15b
22
29
36c, 43c, 
57
85d
113e
180
270
365
545
730 
EOS
q3m
Study Month
1
3
4
6
9
12
18
24
Visit Window 
(days)
+1 ±1
±1
±2
±2
±7
±2
±7
±7
±7
±14
±30 ±30
±30
±30
Abbreviations: AE = adverse event; BMA = bone marrow aspirate; BMB = bone marrow biopsy; CBC = complete blood count; 
 CNS = central nervous 
system; Con = concomitant; Con meds = concomitant medications; CR = complete response; CRS = cytokine release syndrome; CSF = cerebrospinal fluid; CT = computed 
tomography; D = day; ECG = electrocardiogram; ECHO = echocardiogram; ECOG = Eastern Cooperative Oncology Group; EORTC-QLQ-C30 = European Organisation for 
Research and Treatment of Cancer – Quality of Life C30 questionnaire; EOS = end of study; EQ-5D-5L = European Quality of Life-5 Dimensions health state classifier to 5 
Levels; FCBP = female of childbearing potential; GVHD = graft versus host disease; HLA = human leukocyte antigen; HSCT = hematopoietic stem cell transplant; I/E = inclusion 
and exclusion; IPI = international prognostic index; IRT = interactive response technology; IVIG = intravenous immunoglobulins; LD = lymphodepleting chemotherapy; MMSE = 
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5.3.1.
Arm C – For Subjects Continuing CC-220 Beyond Day 85 
Table 14:
Table of Events, Arm C Subjects Continuing CC-220 Beyond Day 85
Study Day
113
141
169
180a
197
225
253
270a
281
309
337b
Visit Window (days)
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
IRT registration
x
x
x
see 
footnote 
a
x
x
x
see 
footnote 
a
x
x
x
ECOG
x
x
x
x
x
x
x
x
x
Weight
x
x
x
x
x
x
x
x
x
Physical examination
x
x
x
x
x
x
x
x
x
Vital signs
x
x
x
x
x
x
x
x
x
Pregnancy testing
x
x
x
x
x
x
x
x
x
Pregnancy prevention counselling
x
x
x
x
x
x
x
x
x
Hematology
x
x
x
x
x
x
x
x
x
Chemistry
x
x
x
x
x
x
x
x
x
Inflammatory markers 
x
x
x
x
x
x
x
x
x
Immunoglobulins
x
x
x
x
x
x
x
x
x
CC-220 administration
see Table 5 for dosing schedule details
Subjects to enter doses taken in diary
Thromboembolic event prophylaxis
x
BMB/BMA 
if clinically indicated
Tumor biopsy
at progressionc
AEs/ Con meds/ Con procedures
all AEs, con meds and con procedures
a For the list of assessments to be performed refer to table of events for Arm C (Table 13).
b Refer to Table 13 for next visit (Day 365).
c If disease progression is assessed, please refer to Section 6.3.3 for the list of assessments to be performed.
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5.4.
Arm D
Table 15:
Table of Events, Arm D
Please refer to the specified protocol section for further details on each procedure.
Protocol 
Section
Pre-JCAR017 Period
JCAR017 Treatment Period
Post-Treatment Period
Survi-
val 
follow-
up
Screening
Leuk
apher
esis
Pre-
lympho-
depletion 
evaluation
Lympho-
depletion 
(start)
Follow-up perioda
Study Day
N/A
-49 to -35
Min. 5D
before 
apheresis
-49 to 
-28
-14 to -7
-10 to -5
1
2
3
4
8
11
15
22
29
57
85
180
270
365
545
730 
EOS
q3m
Study Month
1
3
6
9
12
18
24
Visit Window 
(days)
+1
±1
±1
±2
±2
±7
±7
±7
±14
±14
±30
±30
±30
±30
Obtain consent
6.1.1
xb
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
I/E criteria 
4.2, 4.3
6.1.2  
6.2.1
x
-
x
x
x
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
IRT registration
7.3
x
x
x
x
x
x
-
-
-
x
-
-
-
x
x
x
x
-
-
-
x
-
Medical history
6.1.1
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
IPI 
6.1.1
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
ECOG 
6.4.7
x
-
xc
-
x
x
-
-
-
x
-
x
x
x
x
x
x
x
x
x
x
-
Height
6.4.4
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
Weight
6.4.4
x
-
-
x
-
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
Physical 
examination
6.4.1
xd
-
-
x
-
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
-
Routine neurologic 
examination
6.4.5
x
-
-
x
-
x
x
x
x
x
x
x
x
x
x
x
-
-
-
-
-
-
MMSEe
6.4.5
-
-
-
-
-
x
-
-
x
x
-
x
-
x
x
x
-
-
-
-
-
-
Vital signs
6.4.2
x
-
xc
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
-
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Table 15:
Table of Events, Arm D (Continued)
Protocol 
Section
Pre-JCAR017 Period
JCAR017 Treatment Period
Post-Treatment Period
Survi-
val 
follow
-up
Screening
Leuk
apher
esis
Pre-
lympho-
depletion 
evaluation
Lympho-
depletion 
(start)
Follow-up perioda
Study Day
N/A
-49 to -35
Min. 5D 
before 
apheresis
-49 to
-28
-14 to -7
-10 to -5
1
2
3
4
8
11
15
22
29
57
85
180
270
365
545
730 
EOS
q3m
Study Month
1
3
6
9
12
18
24
Visit Window 
(days)
+1
±1
±1
±2
±2
±7
±7
±7
±14
±14
±30
±30
±30
±30
Pulse oximetry
6.4.3
x
-
-
x
x
x
x
x
x
x
x
x
x
x
x
-
-
-
-
-
-
-
12-lead ECG 
6.4.9
x
-
-
xf
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
MUGA/ECHO 
6.4.8
xg
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
Viral serology 
6.1.1
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
Serum pregnancy 
6.1
x
-
-
-
xh
-
-
-
-
-
-
-
-
-
-
xh
xh
xh
xh
-
-
-
Urinalysis
6.1
x
-
-
-
-
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
CSF assessment
6.4.6
6.7.2
xi
-
-
-
-
if clinically indicated
-
Creatinine 
clearance
6.1
x
-
-
-
xh
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
Hematology 
6.4.12
x
-
xc
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
-
Coagulation
6.4.12
x
-
-
x
-
x
x
x
x
x
x
x
x
x
x
-
-
-
-
-
-
-
Chemistry
6.4.12
x
-
xc
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
-
Inflammatory 
markers 
6.4.12
x
-
-
x
-
x
x
x
x
x
x
x
x
x
x
x
-
-
-
-
-
-
Immunoglobulins
6.4.12
x
-
-
-
-
-
-
-
-
-
-
x
x
x
x
xj
xj
xj
xj
xj
xj
-
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Table 15:
Table of Events, Arm D (Continued)
Protocol 
Section
Pre-JCAR017 Period
JCAR017 Treatment Period
Post-Treatment Period
Survi-
val 
follow
-up
Screening
Leuk
apher
esis
Pre-
lympho-
depletion 
evaluation
Lympho-
depletion 
(start)
Follow-up perioda
Study Day
N/A
-49 to -35
Min. 5D 
before 
apheresis
-49 to
-28
-14 to -7
-10 to -5
1
2
3
4
8
11
15
22
29
57
85
180
270
365
545
730 
EOS
q3m
Study Month
1
3
6
9
12
18
24
Visit Window 
(days)
+1
±1
±1
±2
±2
±7
±7
±7
±14
±14
±30
±30
±30
±30
HLA typing (only 
for subjects with 
prior allogeneic 
HSCT)
6.1.1
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
Donor chimerism 
(only for subjects 
with prior 
allogeneic HSCT)
6.1.1
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
Leukapheresis 
6.1.2
-
-
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
Lymphodepleting 
chemotherapy 
7.2.1
-
-
-
-
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
JCAR017 
administration 
7.2.2
-
-
-
-
-
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
Ibrutinib 
administration
3.1.6
7.2.7
-
see Table 6 for dosing schedule details
Subjects to enter doses taken in diary
-
PET-CT/ MRI
6.5
x
-
-
xf
-
-
-
-
-
-
-
-
-
x
-
x
xk
xk
xk
xk
xk
-
BMB/BMA 
6.1
xl
-
-
-
-
-
-
-
-
-
-
-
-
xm
if clinically indicated
-
Tumor biopsy
6.1
xn
-
-
xf,n
-
-
-
-
-
-
-
-
-
xn
at progressiono
-
Approved
1.0
v

Approved
1.0
v

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Table 15:
Table of Events, Arm D (Continued)
Protocol 
Section
Pre-JCAR017 Period
JCAR017 Treatment Period
Post-Treatment Period
Survi-
val 
follow
-up
Screening
Leuk
apher
esis
Pre-
lympho-
depletion 
evaluation
Lympho-
depletion 
(start)
Follow-up perioda
Study Day
N/A
-49 to -35
Min. 5D 
before 
apheresis
-49 to 
-28
-14 to -7
-10 to -5
1
2
3
4
8
11
15
22
29
57
85
180
270
365
545
730 
EOS
q3m
Study Month
1
3
6
9
12
18
24
Visit Window 
(days)
+1
±1
±1
±2
±2
±7
±7
±7
±14
±14
±30
±30
±30
±30
Approved
1.0
v

Approved
1.0
v

Approved
1.0
v

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5.5.
Arm E
Table 16:
Table of Events, Arm E Cohorts 1A, 1B, 1C
Please refer to the specified protocol section for further details on each procedure.
Protocol 
Section
Pre-JCAR017 Period
JCAR017 Treatment Period
Post-Treatment Period
Survi-
val 
follow-
up
Screening Leukapheresis
Pre-
lympho-
depletion 
evaluation
Lympho-
depletion 
(start)
Follow-up perioda
Study Day
N/A
-49 to -35
-49 to -28
-14 to -7
-10 to -5
1
2
3
4
8
11
15
22
29
36
57
85 180 270 365 545 730 EOS
q3m
Study Month
1
2
3
6
9
12
18
24
Visit Window 
(days)
+1
+4
-1
±1
±2 +4
-2
±7
±7
±7
±7 ±14 ±14 ±30 ±30
±30
±30
Procedures
Obtain consent
6.1.1
xb
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
I/E criteria 
4.2, 4.3
6.1.2  
6.2.1
x
x
x
x
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
IRT registration
7.3
x
x
x
x
x
-
-
-
x
-
-
-
x
x
x
x
x
-
-
-
x
-
Medical history
6.1.1
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
IPI 
6.1.1
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
ECOG 
6.4.7
x
xc
-
x
x
-
-
-
x
-
x
x
x
x
x
x
x
x
x
x
x
-
Height
6.4.4
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
Weight
6.4.4
x
-
x
-
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
Physical 
examination
6.4.1
xd
-
x
-
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
-
Routine 
neurologic 
examination
6.4.5
x
-
x
-
x
x
x
x
x
x
x
x
x
x
x
x
-
-
-
-
-
-
Approved
1.0
v

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Table 16:
Table of Events, Arm E Cohorts 1A, 1B, 1C (Continued)
Protocol 
Section
Pre-JCAR017 Period
JCAR017 Treatment Period
Post-Treatment Period
Survi-
val 
follow-
up
Screening Leukapheresis
Pre-
lympho-
depletion 
evaluation
Lympho-
depletion 
(start)
Follow-up perioda
Study Day
N/A
-49 to -35
-49 to -28
-14 to -7
-10 to -5
1
2
3
4
8
11
15
22
29
36
57
85 180 270 365 545 730 EOS
q3m
Study Month
1
2
3
6
9
12
18
24
Visit Window 
(days)
+1
+4
-1
±1
±2 +4
-2
±7
±7
±7
±7 ±14 ±14 ±30 ±30
±30
±30
MMSEe
6.4.5
-
-
-
-
x
-
-
x
x
-
x
-
x
x
x
x
-
-
-
-
-
-
Vital signsf
6.4.2
x
xc
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
-
Pulse oximetry
6.4.3
x
-
x
x
x
x
x
x
x
x
x
x
x
x
x
-
-
-
-
-
-
-
12-lead ECG 
6.4.9
x
-
xg
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
MUGA/ECHO 
6.4.8
xh
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
Troponin T or I
6.1
x
-
-
-
-
-
-
x
-
-
-
x
-
x
x
x
x
-
-
-
-
-
Viral serology 
6.1.1
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
Serum pregnancy 
6.1
x
-
-
xi
-
-
-
-
xi
-
-
-
-
x
x
xi
xi
xi
xi
-
-
-
Urinalysis
6.1
x
-
-
-
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
CSF assessment
6.4.6
6.7.2
xj
-
-
-
if clinically indicated
-
Creatinine 
clearance
6.1
x
-
-
xi
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
Hematology 
6.4.12
x
xc
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
-
Coagulation
6.4.12
x
-
x
-
x
x
x
x
x
x
x
x
x
x
x
-
-
-
-
-
-
-
Chemistry
6.4.12
x
xc
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
-
Inflammatory 
markers 
6.4.12
x
-
x
-
x
x
x
x
x
x
x
x
x
x
x
x
-
-
-
-
-
-
Approved
1.0
v

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Table 16:
Table of Events, Arm E Cohorts 1A, 1B, 1C (Continued)
Protocol 
Section
Pre-JCAR017 Period
JCAR017 Treatment Period
Post-Treatment Period
Survi-
val 
follow-
up
Screening Leukapheresis
Pre-
lympho-
depletion 
evaluation
Lympho-
depletion 
(start)
Follow-up perioda
Study Day
N/A
-49 to -35
-49 to -28
-14 to -7
-10 to -5
1
2
3
4
8
11
15
22
29
36
57
85 180 270 365 545 730 EOS
q3m
Study Month
1
2
3
6
9
12
18
24
Visit Window 
(days)
+1
+4
-1
±1
±2 +4
-2
±7
±7
±7
±7 ±14 ±14 ±30 ±30
±30
±30
Immunoglobulins
6.4.12
x
-
-
-
-
-
-
-
-
-
x
x
x
x
x
xk
xk
xk
xk
xk
xk
-
Thyroid function 
tests
6.4.12
x
-
-
-
x
-
-
x
-
-
-
x
-
x
x
x
x
-
-
-
-
-
Leukapheresis 
6.1.2
-
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
Lymphodepleting 
chemotherapy 
7.2.1
-
-
-
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
JCAR017 
administration 
7.2.2
-
-
-
-
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
Nivolumab 
infusion
7.2.8
-
-
-
-
-
-
-
-
x
-
-
x
-
x
x
x
-
-
-
-
-
-
Relatlimab 
infusiont
7.2.8
-
-
-
-
-
-
-
-
x
-
-
x
-
x
x
x
-
-
-
-
-
-
Approved
1.0
v

Approved
1.0
v

EDMS Doc. Number: 25256661 - 21712569
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Confidential and Proprietary
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Protocol JCAR017-BCM-002 Amendment 6 Final: 27 Jan 2021
Table 16:
Table of Events, Arm E Cohorts 1A, 1B, 1C (Continued)
Protocol 
Section
Pre-JCAR017 Period
JCAR017 Treatment Period
Post-Treatment Period
Survi-
val 
follow-
up
Screening Leukapheresis
Pre-
lympho-
depletion 
evaluation
Lympho-
depletion 
(start)
Follow-up perioda
Study Day
N/A
-49 to -35
-49 to -28
-14 to -7
-10 to -5
1
2
3
4
8
11
15
22
29
36
57
85 180 270 365 545 730 EOS
q3m
Study Month
1
2
3
6
9
12
18
24
Visit Window 
(days)
+1
+4
-1
±1
±2 +4
-2
±7
±7
±7
±7 ±14 ±14 ±30 ±30
±30
±30
Approved
1.0
v

EDMS Doc. Number: 25256661 - 21712569
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Protocol JCAR017-BCM-002 Amendment 6 Final: 27 Jan 2021
Table 16:
Table of Events, Arm E Cohorts 1A, 1B, 1C (Continued)
Protocol 
Section
Pre-JCAR017 Period
JCAR017 Treatment Period
Post-Treatment Period
Survi-
val 
follow-
up
Screening Leukapheresis
Pre-
lympho-
depletion 
evaluation
Lympho-
depletion 
(start)
Follow-up perioda
Study Day
N/A
-49 to -35
-49 to -28
-14 to -7
-10 to -5
1
2
3
4
8
11
15
22
29
36
57
85 180 270 365 545 730 EOS
q3m
Study Month
1
2
3
6
9
12
18
24
Visit Window 
(days)
+1
+4
-1
±1
±2 +4
-2
±7
±7
±7
±7 ±14 ±14 ±30 ±30
±30
±30
Approved
1.0
v

Approved
1.0
v

Approved
1.0
v

EDMS Doc. Number: 25256661 - 21712569
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Table 17:
Table of Events, Arm E Cohorts 1A+1, 1B+1, 1C+1
Protocol 
Section
Pre-JCAR017 Period
JCAR017 Treatment Period
Post-Treatment Period
Survi-
val 
follow-
up
Screening Leukapheresis
Pre-
lympho-
depletion 
evaluation
Lympho-
depletion 
(start)
Follow-up perioda
Study Day
N/A
-49 to -35
-49 to -28
-14 to -7
-10 to -5
1
2
3
4
8
11
15 22
29
36
57
85 180 270 365 545 730 EOS
q3m
Study Month
1
2
3
6
9
12
18
24
Visit Window 
(days)
+1
+4
-1
±1
±2 ±2 ±7
±7
±7
±7 ±14 ±14 ±30 ±30
±30
±30
Procedures
Obtain consent
6.1.1
xb
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
I/E criteria 
4.2, 4.3
6.1.2  
6.2.1
x
x
x
x
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
IRT registration
7.3
x
x
x
x
x
-
-
-
x
-
-
-
x
x
x
x
x
-
-
-
x
-
Medical history
6.1.1
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
IPI 
6.1.1
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
ECOG 
6.4.7
x
xc
-
x
x
-
-
-
x
-
x
x
x
x
x
x
x
x
x
x
x
-
Height
6.4.4
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
Weight
6.4.4
x
-
x
-
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
Physical 
examination
6.4.1
xd
-
x
-
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
-
Routine 
neurologic 
examination
6.4.5
x
-
x
-
x
x
x
x
x
x
x
x
x
x
x
x
-
-
-
-
-
-
Approved
1.0
v

EDMS Doc. Number: 25256661 - 21712569
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Table 17:
Table of Events, Arm E Cohorts 1A+1, 1B+1, 1C+1 (Continued)
Protocol 
Section
Pre-JCAR017 Period
JCAR017 Treatment Period
Post-Treatment Period
Survi-
val 
follow-
up
Screening Leukapheresis
Pre-
lympho-
depletion 
evaluation
Lympho-
depletion 
(start)
Follow-up perioda
Study Day
N/A
-49 to -35
-49 to -28
-14 to -7
-10 to -5
1
2
3
4
8
11
15 22
29
36
57
85 180 270 365 545 730 EOS
q3m
Study Month
1
2
3
6
9
12
18
24
Visit Window 
(days)
+1
+4
-1
±1
±2 ±2 ±7
±7
±7
±7 ±14 ±14 ±30 ±30
±30
±30
MMSEe
6.4.5
-
-
-
-
x
-
-
x
x
-
x
-
x
x
x
x
-
-
-
-
-
-
Vital signsf
6.4.2
x
xc
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
-
Pulse oximetry
6.4.3
x
-
x
x
x
x
x
x
x
x
x
x
x
x
x
-
-
-
-
-
-
-
12-lead ECG 
6.4.9
x
-
xg
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
MUGA/ECHO 
6.4.8
xh
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
Troponin T or I
6.1
x
-
-
-
-
-
-
x
-
-
-
-
-
x
x
x
x
-
-
-
-
-
Viral serology 
6.1.1
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
Serum pregnancy 
6.1
x
-
-
xi
-
-
-
-
xi
-
-
-
-
x
x
xi
xi
xi
xi
-
-
-
Urinalysis
6.1
x
-
-
-
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
CSF assessment
6.4.6
6.7.2
xj
-
-
-
if clinically indicated
-
Creatinine 
clearance
6.1
x
-
-
xi
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
Hematology 
6.4.12
x
xc
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
-
Coagulation
6.4.12
x
-
x
-
x
x
x
x
x
x
x
x
x
x
x
-
-
-
-
-
-
-
Chemistry
6.4.12
x
xc
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
-
Inflammatory 
markers 
6.4.12
x
-
x
-
x
x
x
x
x
x
x
x
x
x
x
x
-
-
-
-
-
-
Approved
1.0
v

EDMS Doc. Number: 25256661 - 21712569
JCAR017
Protocol JCAR017-BCM-002
Celgene Corporation
Confidential and Proprietary
125
Protocol JCAR017-BCM-002 Amendment 6 Final: 27 Jan 2021
Table 17:
Table of Events, Arm E Cohorts 1A+1, 1B+1, 1C+1 (Continued)
Protocol 
Section
Pre-JCAR017 Period
JCAR017 Treatment Period
Post-Treatment Period
Survi-
val 
follow-
up
Screening Leukapheresis
Pre-
lympho-
depletion 
evaluation
Lympho-
depletion 
(start)
Follow-up perioda
Study Day
N/A
-49 to -35
-49 to -28
-14 to -7
-10 to -5
1
2
3
4
8
11
15 22
29
36
57
85 180 270 365 545 730 EOS
q3m
Study Month
1
2
3
6
9
12
18
24
Visit Window 
(days)
+1
+4
-1
±1
±2 ±2 ±7
±7
±7
±7 ±14 ±14 ±30 ±30
±30
±30
Immunoglobulins
6.4.12
x
-
-
-
-
-
-
-
-
-
x
x
x
x
x
xk
xk
xk
xk
xk
xk
-
Thyroid function 
tests
6.4.12
x
-
-
-
x
-
-
x
-
-
-
-
-
x
x
x
x
-
-
-
-
-
Leukapheresis 
6.1.2
-
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
Lymphodepleting 
chemotherapy 
7.2.1
-
-
-
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
JCAR017 
administration 
7.2.2
-
-
-
-
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
Nivolumab 
infusion
7.2.8
-
-
-
-
-
-
-
-
x
-
-
-
-
x
x
x
-
-
-
-
-
-
Relatlimab 
infusiont
7.2.8
-
-
-
-
-
-
-
-
x
-
-
-
-
x
x
x
-
-
-
-
-
-
Approved
1.0
v

Approved
1.0
v

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127
Protocol JCAR017-BCM-002 Amendment 6 Final: 27 Jan 2021
Table 17:
Table of Events, Arm E Cohorts 1A+1, 1B+1, 1C+1 (Continued)
Protocol 
Section
Pre-JCAR017 Period
JCAR017 Treatment Period
Post-Treatment Period
Survi-
val 
follow-
up
Screening Leukapheresis
Pre-
lympho-
depletion 
evaluation
Lympho-
depletion 
(start)
Follow-up perioda
Study Day
N/A
-49 to -35
-49 to -28
-14 to -7
-10 to -5
1
2
3
4
8
11
15 22
29
36
57
85 180 270 365 545 730 EOS
q3m
Study Month
1
2
3
6
9
12
18
24
Visit Window 
(days)
+1
+4
-1
±1
±2 ±2 ±7
±7
±7
±7 ±14 ±14 ±30 ±30
±30
±30
Approved
1.0
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128
Protocol JCAR017-BCM-002 Amendment 6 Final: 27 Jan 2021
Table 17:
Table of Events, Arm E Cohorts 1A+1, 1B+1, 1C+1 (Continued)
Protocol 
Section
Pre-JCAR017 Period
JCAR017 Treatment Period
Post-Treatment Period
Survi-
val 
follow-
up
Screening Leukapheresis
Pre-
lympho-
depletion 
evaluation
Lympho-
depletion 
(start)
Follow-up perioda
Study Day
N/A
-49 to -35
-49 to -28
-14 to -7
-10 to -5
1
2
3
4
8
11
15 22
29
36
57
85 180 270 365 545 730 EOS
q3m
Study Month
1
2
3
6
9
12
18
24
Visit Window 
(days)
+1
+4
-1
±1
±2 ±2 ±7
±7
±7
±7 ±14 ±14 ±30 ±30
±30
±30
Approved
1.0
v

Approved
1.0
v

Approved
1.0
v

EDMS Doc. Number: 25256661 - 21712569
JCAR017
Protocol JCAR017-BCM-002
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Confidential and Proprietary
131
Protocol JCAR017-BCM-002 Amendment 6 Final: 27 Jan 2021
Table 18:
Table of Events, Arm E Cohorts 1A-1, 1B-1, 1C-1
Protocol 
Section
Pre-JCAR017 Period
JCAR017 Treatment Period
Post-Treatment Period
Survi-
val 
follow-
up
Screening Leukapheresis
Pre-
lympho-
depletion 
evaluation
Lympho-
depletion 
(start)
Follow-up Perioda
Study Day
N/A
-49 to -35
-49 to -28
-14 to -7
-10 to -5
1
2
3
4
8
11
15
22
29
43
57 85 180 270 365 545 730 EOS
q3m
Study Month
1
2
3
6
9
12
18
24
Visit Window 
(days)
+1
±1
±1
+4
-1
±2
±7
±7
±7 ±7 ±14 ±14 ±30 ±30
±30
±30
Procedures
Obtain consent
6.1.1
xb
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
I/E criteria 
4.2, 4.3
6.1.2  
6.2.1
x
x
x
x
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
IRT registration
7.3
x
x
x
x
x
-
-
-
x
-
-
-
x
x
x
x
x
-
-
-
x
-
Medical history
6.1.1
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
IPI 
6.1.1
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
ECOG 
6.4.7
x
xc
-
x
x
-
-
-
x
-
x
x
x
x
x
x
x
x
x
x
x
-
Height
6.4.4
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
Weight
6.4.4
x
-
x
-
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
Physical 
examination
6.4.1
xd
-
x
-
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
-
Routine 
neurologic 
examination
6.4.5
x
-
x
-
x
x
x
x
x
x
x
x
x
x
x
x
-
-
-
-
-
-
MMSEe
6.4.5
-
-
-
-
x
-
-
x
x
-
x
-
x
x
x
x
-
-
-
-
-
-
Vital signsf
6.4.2
x
xc
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
-
Pulse oximetry
6.4.3
x
-
x
x
x
x
x
x
x
x
x
x
x
x
x
-
-
-
-
-
-
-
Approved
1.0
v

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JCAR017
Protocol JCAR017-BCM-002
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Confidential and Proprietary
132
Protocol JCAR017-BCM-002 Amendment 6 Final: 27 Jan 2021
Table 18:
Table of Events, Arm E Cohorts 1A-1, 1B-1, 1C-1 (Continued)
Protocol 
Section
Pre-JCAR017 Period
JCAR017 Treatment Period
Post-Treatment Period
Survi-
val 
follow
-up
Screening Leukapheresis
Pre-
lympho-
depletion 
evaluatio
n
Lympho-
depletion 
(start)
Follow-up Perioda
Study Day
N/A
-49 to -35
-49 to -28
-14 to -7
-10 to -5
1
2
3
4
8
11
15
22
29
43
57
85
180 270 365 545 730 EOS
q3m
Study Month
1
2
3
6
9
12
18
24
Visit Window 
(days)
+1
±1
±1
+4
-1
±2
±7 ±7
±7
±7 ±14 ±14 ±30 ±30
±30
±30
12-lead ECG 
6.4.9
x
-
xg
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
MUGA/ECHO 
6.4.8
xh
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
Troponin T or I
6.1
x
-
-
-
-
-
-
-
-
x
-
-
x
x
x
x
x
-
-
-
-
-
Viral serology 
6.1.1
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
Serum pregnancy 
6.1
x
-
-
xi
-
-
-
-
-
-
xh
-
-
x
x
xi
xi
xi
xi
-
-
-
Urinalysis
6.1
x
-
-
-
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
CSF assessment
6.4.6
6.7.2
xj
-
-
-
if clinically indicated
-
Creatinine 
clearance
6.1
x
-
-
xi
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
Hematology 
6.4.12
x
xc
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
-
Coagulation
6.4.12
x
-
x
-
x
x
x
x
x
x
x
x
x
x
x
-
-
-
-
-
-
-
Chemistry
6.4.12
x
xc
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
-
Inflammatory 
markers 
6.4.12
x
-
x
-
x
x
x
x
x
x
x
x
x
x
x
x
-
-
-
-
-
-
Immunoglobulins
6.4.12
x
-
-
-
-
-
-
-
-
-
x
x
x
x
x
xk
xk
xk
xk
xk
xk
-
Thyroid function 
tests
6.4.12
x
-
-
-
x
-
-
-
-
x
-
-
x
x
x
x
x
-
-
-
-
-
Approved
1.0
v

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JCAR017
Protocol JCAR017-BCM-002
Celgene Corporation
Confidential and Proprietary
133
Protocol JCAR017-BCM-002 Amendment 6 Final: 27 Jan 2021
Table 18:
Table of Events, Arm E Cohorts 1A-1, 1B-1, 1C-1 (Continued)
Protocol 
Section
Pre-JCAR017 Period
JCAR017 Treatment Period
Post-Treatment Period
Survi-
val 
follow-
up
Screening Leukapheresis
Pre-
lympho-
depletion 
evaluation
Lympho-
depletion 
(start)
Follow-up Perioda
Study Day
N/A
-49 to -35
-49 to -28
-14 to -7
-10 to -5
1
2
3
4
8
11
15
22
29
43
57 85 180 270 365 545 730 EOS
q3m
Study Month
1
2
3
6
9
12
18
24
Visit Window 
(days)
+1
±1
±1
+4
-1
±2
±7
±7 ±7 ±7 ±14 ±14 ±30 ±30
±30
±30
Leukapheresis 
6.1.2
-
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
Lymphodepleting 
chemotherapy 
7.2.1
-
-
-
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
JCAR017 
administration 
7.2.2
-
-
-
-
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
Nivolumab 
infusion
7.2.8
-
-
-
-
-
-
-
-
-
-
x
-
x
x
x
x
-
-
-
-
-
-
Relatlimab 
infusiont
7.2.8
-
-
-
-
-
-
-
-
-
-
x
-
x
x
x
x
-
-
-
-
-
-
PET-CT/ MRI
6.5
x
-
xg
-
-
-
-
-
-
-
-
-
x
-
-
x
xl
xl
xl
xl
xl
-
BMB/BMA 
6.1
xm
-
-
-
-
-
-
-
-
-
-
-
xn
if clinically indicated
-
Tumor biopsy
6.1
xo
-
xg,o
-
-
-
-
-
-
-
-
-
xo
at progressionp
-
Approved
1.0
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EDMS Doc. Number: 25256661 - 21712569
JCAR017
Protocol JCAR017-BCM-002
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Confidential and Proprietary
135
Protocol JCAR017-BCM-002 Amendment 6 Final: 27 Jan 2021
Table 18:
Table of Events, Arm E Cohorts 1A-1, 1B-1, 1C-1 (Continued)
Protocol 
Section
Pre-JCAR017 Period
JCAR017 Treatment Period
Post-Treatment Period
Survi-
val 
follow-
up
Screening Leukapheresis
Pre-
lympho-
depletion 
evaluation
Lympho-
depletion 
(start)
Follow-up Perioda
Study Day
N/A
-49 to -35
-49 to -28
-14 to -7
-10 to -5
1
2
3
4
8
11
15
22
29
43
57
85 180 270 365 545 730 EOS
q3m
Study Month
1
2
3
6
9
12
18
24
Visit Window 
(days)
+1 ±1 ±1 +4
-1
±2
±7
±7
±7 ±7 ±14 ±14 ±30 ±30
±30
±30
Approved
1.0
v

EDMS Doc. Number: 25256661 - 21712569
JCAR017
Protocol JCAR017-BCM-002
Celgene Corporation
Confidential and Proprietary
136
Protocol JCAR017-BCM-002 Amendment 6 Final: 27 Jan 2021
Table 18:
Table of Events, Arm E Cohorts 1A-1, 1B-1, 1C-1 (Continued)
Protocol 
Section
Pre-JCAR017 Period
JCAR017 Treatment Period
Post-Treatment Period
Survi-
val 
follow-
up
Screening Leukapheresis
Pre-
lympho-
depletion 
evaluation
Lympho-
depletion 
(start)
Follow-up Perioda
Study Day
N/A
-49 to -35
-49 to -28
-14 to -7
-10 to -5
1
2
3
4
8
11
15
22
29
43
57
85 180 270 365 545 730 EOS
q3m
Study Month
1
2
3
6
9
12
18
24
Visit Window 
(days)
+1 ±1 ±1 +4
-1
±2
±7
±7
±7 ±7 ±14 ±14 ±30 ±30
±30
±30
Abbreviations: AE = adverse event; BMA = bone marrow aspirate; BMB = bone marrow biopsy; CBC = complete blood count; 
; CNS = central nervous 
system; Con = concomitant; Con meds = concomitant medications; CR = complete response; CRS = cytokine release syndrome; CSF = cerebrospinal fluid; CT = computed 
tomography; D = day; diff = differential; ECG = electrocardiogram; ECHO = echocardiogram; ECOG = Eastern Cooperative Oncology Group; EORTC-QLQ-C30 = European 
Organisation for Research and Treatment of Cancer – Quality of Life C30 questionnaire; EOS = end of study; EQ-5D-5L = European Quality of Life-5 Dimensions health state 
classifier to 5 Levels; FCBP = female of childbearing potential ; GVHD = graft versus host disease; I/E = inclusion and exclusion; IPI = international prognostic index; IRT = 
interactive response technology; IVIG = intravenous immunoglobulins; LD = lymphodepleting; MMSE = Mini Mental State Examination; MRI= magnetic resonance imaging; 
Approved
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EDMS Doc. Number: 25256661 - 21712569
JCAR017
Protocol JCAR017-BCM-002
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Confidential and Proprietary
138
Protocol JCAR017-BCM-002 Amendment 6 Final: 27 Jan 2021
Table 19:
Table of Events, Arm E Cohorts 1A+2, 1B+2, 1C+2
Protocol 
Section
Pre-JCAR017 Period
JCAR017 Treatment Period
Post-Treatment Period
Survi-
val 
follow-
up
Screening Leukapheresis
Pre-
lympho-
depletion 
evaluation
Lympho-
depletion 
(start)
Follow-up perioda
Study Day
N/A
-49 to -35
-49 to -28
-14 to -7
-10 to -5
1
2
3
4
8
11
15
22
29
43
57 85 180 270 365 545 730 EOS
q3m
Study Month
1
2
3
6
9
12
18
24
Visit Window 
(days)
+1
+4
-1
±1
±2
±2
±7
±7
±7 ±7 ±14 ±14 ±30 ±30
±30
±30
Procedure
Obtain consent
6.1.1
xb
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
I/E criteria 
4.2, 4.3
6.1.2  
6.2.1
x
x
x
x
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
IRT registration
7.3
x
x
x
x
x
-
-
-
x
-
-
-
x
x
x
x
x
-
-
-
x
-
Medical history
6.1.1
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
IPI 
6.1.1
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
ECOG 
6.4.7
x
xc
-
x
x
-
-
-
x
-
x
x
x
x
x
x
x
x
x
x
x
-
Height
6.4.4
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
Weight
6.4.4
x
-
x
-
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
Physical 
examination
6.4.1
xd
-
x
-
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
-
Routine 
neurologic 
examination
6.4.5
x
-
x
-
x
x
x
x
x
x
x
x
x
x
x
x
-
-
-
-
-
-
MMSEe
6.4.5
-
-
-
-
x
-
-
x
x
-
x
-
x
x
x
x
-
-
-
-
-
-
Vital signsf
6.4.2
x
xc
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
-
Pulse oximetry
6.4.3
x
-
x
x
x
x
x
x
x
x
x
x
x
x
x
-
-
-
-
-
-
-
Approved
1.0
v

EDMS Doc. Number: 25256661 - 21712569
JCAR017
Protocol JCAR017-BCM-002
Celgene Corporation
Confidential and Proprietary
139
Protocol JCAR017-BCM-002 Amendment 6 Final: 27 Jan 2021
Table 19:
Table of Events, Arm E Cohorts 1A+2, 1B+2, 1C+2 (Continued)
Protocol 
Section
Pre-JCAR017 Period
JCAR017 Treatment Period
Post-Treatment Period
Survi-
val 
follow
-up
Screening Leukaphe-
resis
Pre-lympho-
depletion 
evaluation
Lympho-
depletion 
(start)
Follow-up perioda
Study Day
N/A
-49 to -35
-49 to -28
-14 to -7
-10 to -5
1
2
3
4
8
11
15 22 29 43
57
85 180 270 365 545 730 EOS
q3m
Study Month
1
2
3
6
9
12
18
24
Visit Window 
(days)
+1 +4
-1
±1 ±2 ±2 ±7 ±7 ±7
±7 ±14 ±14 ±30 ±30
±30
±30
12-lead ECG 
6.4.9
x
-
xg
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
MUGA/ECHO 
6.4.8
xh
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
Troponin T or I
6.1
x
-
-
-
-
-
-
-
-
x
-
-
x
x
x
x
x
-
-
-
-
-
Viral serology 
6.1.1
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
Serum pregnancy 
6.1
x
-
-
xi
-
-
-
-
-
-
xi
-
-
x
x
xi
xi
xi
xi
-
-
-
Urinalysis
6.1
x
-
-
-
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
CSF assessment
6.4.6
6.7.2
xj
-
-
-
if clinically indicated
-
Creatinine 
clearance
6.1
x
-
-
xi
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
Hematology 
6.4.12
x
xc
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
-
Coagulation
6.4.12
x
-
x
-
x
x
x
x
x
x
x
x
x
x
x
-
-
-
-
-
-
-
Chemistry
6.4.12
x
xc
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
-
Inflammatory 
markers 
6.4.12
x
-
x
-
x
x
x
x
x
x
x
x
x
x
x
x
-
-
-
-
-
-
Immunoglobulins
6.4.12
x
-
-
-
-
-
-
-
-
-
x
x
x
x
x
xk
xk
xk
xk
xk
xk
-
Thyroid function 
tests
6.4.12
x
-
-
-
x
-
-
-
-
x
-
-
x
-
x
x
x
-
-
-
-
-
Approved
1.0
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Table 19:
Table of Events, Arm E Cohorts 1A+2, 1B+2, 1C+2 (Continued)
Protocol 
Section
Pre-JCAR017 Period
JCAR017 Treatment Period
Post-Treatment Period
Survi-
val 
follow-
up
Screening Leukapheresis
Pre-lympho-
depletion 
evaluation
Lympho-
depletion 
(start)
Follow-up perioda
Study Day
N/A
-49 to -35
-49 to -28
-14 to -7
-10 to -5
1
2
3
4
8
11
15
22
29
43
57 85 180 270 365 545 730 EOS
q3m
Study Month
1
2
3
6
9
12
18
24
Visit Window 
(days)
+1 +4
-1
±1 ±2 ±2 ±7
±7
±7 ±7 ±14 ±14 ±30 ±30
±30
±30
Leukapheresis 
6.1.2
-
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
Lymphodepleting 
chemotherapy 
7.2.1
-
-
-
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
JCAR017 
administration 
7.2.2
-
-
-
-
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
Nivolumab 
infusion
7.2.8
-
-
-
-
-
-
-
-
-
-
x
-
-
-
x
x
-
-
-
-
-
-
Relatlimab 
infusiont
7.2.8
-
-
-
-
-
-
-
-
-
-
x
-
-
-
x
x
-
-
-
-
-
-
PET-CT/ MRI
6.5
x
-
xg
-
-
-
-
-
-
-
-
-
x
-
-
x
xl
xl
xl
xl
xl
-
BMB/BMA 
6.1
xm
-
-
-
-
-
-
-
-
-
-
-
xn
if clinically indicated
-
Tumor biopsy
6.1
xo
-
xg,o
-
-
-
-
-
-
-
-
-
xo
at progressionp
-
Approved
1.0
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Table 19:
Table of Events, Arm E Cohorts 1A+2, 1B+2, 1C+2 (Continued)
Protocol 
Section
Pre-JCAR017 Period
JCAR017 Treatment Period
Post-Treatment Period
Survi-
val 
follow-
up
Screening Leukapheresis
Pre-
lympho-
depletion 
evaluation
Lympho-
depletion 
(start)
Follow-up perioda
Study Day
N/A
-49 to -35
-49 to -28
-14 to -7
-10 to -5
1
2
3
4
8
11 15 22
29
43
57
85 180 270 365 545 730 EOS
q3m
Study Month
1
2
3
6
9
12
18
24
Visit Window 
(days)
+1 +4
-1 ±1 ±2 ±2 ±7
±7
±7 ±7 ±14 ±14 ±30 ±30
±30
±30
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1.0
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Protocol JCAR017-BCM-002 Amendment 6 Final: 27 Jan 2021
Table 19:
Table of Events, Arm E Cohorts 1A+2, 1B+2, 1C+2 (Continued)
Protocol 
Section
Pre-JCAR017 Period
JCAR017 Treatment Period
Post-Treatment Period
Survi-
val 
follow-
up
Screening Leukapheresis
Pre-
lympho-
depletion 
evaluation
Lympho-
depletion 
(start)
Follow-up perioda
Study Day
N/A
-49 to -35
-49 to -28
-14 to -7
-10 to -5
1
2
3
4
8
11
15
22
29
43
57
85 180 270 365 545 730 EOS
q3m
Study Month
1
2
3
6
9
12
18
24
Visit Window 
(days)
+1 +4
-1
±1 ±2 ±2
±7
±7
±7 ±7 ±14 ±14 ±30 ±30
±30
±30
Abbreviations: AE = adverse event; BMA = bone marrow aspirate; BMB = bone marrow biopsy; CBC = complete blood count;
; CNS = central nervous 
system; Con = concomitant; Con meds = concomitant medications; CR = complete response; CRS = cytokine release syndrome; CSF = cerebrospinal fluid; CT = computed 
tomography; D = day; diff = differential; ECG = electrocardiogram; ECHO = echocardiogram; ECOG = Eastern Cooperative Oncology Group; EORTC-QLQ-C30 = European 
Organisation for Research and Treatment of Cancer – Quality of Life C30 questionnaire; EOS = end of study; EQ-5D-5L = European Quality of Life-5 Dimensions health state 
classifier to 5 Levels; FCBP = female of childbearing potential ; GVHD = graft versus host disease; I/E = inclusion and exclusion; IPI = international prognostic index; IRT = 
interactive response technology; IVIG = intravenous immunoglobulins; LD = lymphodepleting; MMSE = Mini Mental State Examination; MRI= magnetic resonance imaging; 
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5.6.
Arm F
Table 20:
Table of Events, Arm F 
Please refer to the specified protocol section for further details on each procedure.
Protocol 
Section
Pre-JCAR017 Period
JCAR017 Treatment Period
Post-Treatment Period
Survival 
follow-up
Screenin
g
Leukapheresi
s
Pre-
lympho-
depletion 
evaluatio
n
Lympho
-
depletio
n (start)
Follow-up perioda
Study Day
N/A
-49 to -35
-49 to -28
-14 to -7
-10 to -5
1
2
3
4
8
11
15
22
29
57
85
180
270
365
545
730 
EOS
q3m
Study Month
1
3
6
9
12
18
24
Visit Window 
(days)
+1
±1
±1
±2
±2
±7
±7
±7
±14
±14
±30
±30
±30
±30
Procedures
Obtain consent
6.1.1
xb
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
I/E criteria 
4.2, 4.3
6.1.2  
6.2.1
x
x
x
x
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
IRT registration
7.3
x
x
x
x
x
-
-
-
x
-
-
-
x
x
x
x
-
-
-
x
-
Medical history
6.1.1
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
IPI 
6.1.1
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
ECOG 
6.4.7
x
xc
-
x
x
-
-
-
x
-
x
x
x
x
x
x
x
x
x
x
-
Height
6.4.4
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
Weight
6.4.4
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
Physical 
examination
6.4.1
xd
-
x
-
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
-
Routine 
neurologic 
examination
6.4.5
x
-
x
-
x
x
x
x
x
x
x
x
x
x
x
-
-
-
-
-
-
MMSEe
6.4.5
-
-
-
-
x
-
-
x
x
-
x
-
x
x
x
-
-
-
-
-
-
Approved
1.0
v

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Table 20:
Table of Events, Arm F (Continued)
Protocol 
Section
Pre-JCAR017 Period
JCAR017 Treatment Period
Post-Treatment Period
Survi-val 
follow-up
Screenin
g
Leukapheresi
s
Pre-
lympho-
depletion 
evaluatio
n
Lympho
-
depletio
n (start)
Follow-up perioda
Study Day
N/A
-49 to -35
-49 to -28
-14 to -7
-10 to -5
1
2
3
4
8
11
15
22
29
57
85
180
270
365
545
730 
EOS
q3m
Study Month
1
3
6
9
12
18
24
Visit Window 
(days)
+1
±1
±1
±2
±2
±7
±7
±7
±14
±14
±30
±30
±30
±30
Vital signs
6.4.2
x
xc
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
-
Pulse oximetry
6.4.3
x
-
x
x
x
x
x
x
x
x
x
x
x
x
-
-
-
-
-
-
-
12-lead ECG 
6.4.9
x
-
xf
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
MUGA/ECHO 
6.4.8
xg
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
Viral serology 
6.1.1
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
Serum 
pregnancy
6.1
xh
-
-
xh
xh
-
-
-
xh
-
xh
-
xh
xh
xh
xh
xh
xh
-
-
-
Pregnancy 
Prevention 
Counselling
6.1
x
-
-
x
x
-
-
-
x
-
x
-
x
x
x
-
-
-
-
-
-
Urinalysis
6.1
x
-
-
-
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
CSF assessment
6.4.6
6.7.2
xi
-
-
-
ici
-
Creatinine 
clearance
6.1
x
-
-
xh
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
Hematology 
6.4.12
x
xc
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
-
Coagulation
6.4.12
x
-
x
-
x
x
x
x
x
x
x
x
x
x
-
-
-
-
-
-
-
Approved
1.0
v

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JCAR017
Protocol JCAR017-BCM-002
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Confidential and Proprietary
147
Protocol JCAR017-BCM-002 Amendment 6 Final: 27 Jan 2021
Table 20:
Table of Events, Arm F (Continued)
Protocol 
Section
Pre-JCAR017 Period
JCAR017 Treatment Period
Post-Treatment Period
Survival 
follow-up
Screenin
g
Leukapheresi
s
Pre-
lympho-
depletion 
evaluatio
n
Lympho
-
depletio
n (start)
Follow-up perioda
Study Day
N/A
-49 to -35
-49 to -28
-14 to -7
-10 to -5
1
2
3
4
8
11
15
22
29
57
85
180
270
365
545
730 
EOS
q3m
Study Month
1
3
6
9
12
18
24
Visit Window 
(days)
+1
±1
±1
±2
±2
±7
±7
±7
±14
±14
±30
±30
±30
±30
Inflammatory 
markers 
6.4.12
x
-
x
-
x
x
x
x
x
x
x
x
x
x
x
-
-
-
-
-
-
Immunoglobulin
s
6.4.12
x
-
-
-
-
-
-
-
-
-
x
x
x
x
xj
xj
xj
xj
xj
xj
-
HLA typing 
(only for 
subjects with 
prior allogeneic 
HSCT)
6.1.1
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
Donor 
chimerism (only 
for subjects with 
prior allogeneic 
HSCT)
6.1.1
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
Leukapheresis 
6.1.2
-
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
Lymphodepletin
g chemotherapy 
7.2.1
-
-
-
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
JCAR017 
administration 
7.2.2
-
-
-
-
x
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
Approved
1.0
v

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1.0
v

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Table 20:
Table of Events, Arm F (Continued)
Protocol 
Section
Pre-JCAR017 Period
JCAR017 Treatment Period
Post-Treatment Period
Surv
ival 
follo
w-up
Screenin
g
Leukapheresis
Pre-
lympho-
depletion 
evaluation
Lympho-
depletion 
(start)
Follow-up perioda
Study Day
N/A
-49 to -35
-49 to -28
-14 to -7
-10 to -5
1
2
3
4
8
11
15
22
29
57
85
180
270
365
545
730 
EOS
q3m
Study Month
1
3
6
9
12
18
24
Visit Window 
(days)
+1
±1
±1
±2
±2
±7
±7
±7
±14
±14
±30
±30
±30
±30
Disease 
therapy since 
study 
treatment 
discontinuati
on
6.3.1
-
-
-
-
Anticancer treatment since JCAR017
Survival 
status
6.3.7
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
x
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Table 20:
Table of Events, Arm F (Continued)
Protocol 
Section
Pre-JCAR017 Period
JCAR017 Treatment Period
Post-Treatment Period
Surv
i-val 
follo
w-up
Screenin
g
Leukapheresis
Pre-
lympho-
depletion 
evaluation
Lympho-
depletion 
(start)
Follow-up perioda
Study Day
N/A
-49 to -
35
-49 to -28
-14 to -7
-10 to -5
1
2
3
4
8
11
15
22
29
57
85
180
270
365
545
730 
EO
S
q3m
Study Month
1
3
6
9
12
18
24
Visit Window 
(days)
+1
±1
±1
±2
±2
±7
±7
±7
±14
±14
±30
±30
±30
±30
Approved
1.0
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Table 20:
Table of Events, Arm F (Continued)
Protocol 
Section
Pre-JCAR017 Period
JCAR017 Treatment Period
Post-Treatment Period
Survi-val 
follow-up
Screenin
g
Leukapheresi
s
Pre-
lympho-
depletion 
evaluatio
n
Lympho
-
depletio
n (start)
Follow-up perioda
Study Day
N/A
-49 to -35
-49 to -28
-14 to -7
-10 to -5
1
2
3
4
8
11
15
22
29
57
85
180
270
365
545
730 
EOS
q3m
Study Month
1
3
6
9
12
18
24
Visit Window 
(days)
+1
±1
±1
±2
±2
±7
±7
±7
±14
±14
±30
±30
±30
±30
Abbreviations: AE = adverse event; BMA = bone marrow aspirate; BMB = bone marrow biopsy; CBC = complete blood count; 
; CNS = central nervous 
system; Con = concomitant; Con meds = concomitant medications; CR = complete response; CRS = cytokine release syndrome; CSF = cerebrospinal fluid; CT = computed 
tomography; D = day; diff = differential; ECG = electrocardiogram; ECHO = echocardiogram; ECOG = Eastern Cooperative Oncology Group; EORTC-QLQ-C30 = European 
Organisation for Research and Treatment of Cancer – Quality of Life C30 questionnaire; EOS = end of study; EQ-5D-5L = European Quality of Life-5 Dimensions health state 
classifier to 5 Levels; FCBP = female of childbearing potential; GVHD = graft versus host disease; HLA = human leukocyte antigen; HSCT = hematopoietic stem cell transplant; 
I/E = inclusion and exclusion; IPI = international prognostic index; IRT = interactive response technology; IVIG = intravenous immunoglobulins; LD = lymphodepleting; MMSE 
= Mini Mental State Examination; MRI= magnetic resonance imaging; MUGA = multi-gated acquisition scan; N/A = not applicable; 
; 
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6.
PROCEDURES
Any questions regarding the protocol should be directed to the Medical Monitor(s) or designee. 
Tables of Events are provided as indicated in Table 21.
Table 21:
Links to Tables of Events
Arm and Cohort
Table of Events
Arm A Cohort 1
Table 10
Arm A Cohort 1A-2
Table 11
Arm B Cohort 1
Table 12
Arm C 
Table 13
Arm C – subjects continuing CC-220 beyond Day 85
Table 14
Arm D 
Table 15
Arm E Cohorts 1A, 1B, 1C
Table 16
Arm E Cohorts 1A+1, 1B+1, 1C+1
Table 17
Arm E Cohorts 1A-1, 1B-1, 1C-1
Table 18
Arm E Cohorts 1A+2, 1B+2, 1C+2
Table 19
Arm F
Table 20
6.1.
Pre-Treatment Period
6.1.1.
Screening (Approximately 1 to 2 Weeks Prior to Leukapheresis)
Screening evaluations will be performed for all subjects to determine study eligibility. These 
evaluations should be completed within approximately 1 to 2 weeks of leukapheresis unless 
noted otherwise below. For Arm D, screening evaluations are to be performed a maximum of
3 weeks prior to leukapheresis in order to allow exposure to ibrutinib for at least 5 days prior to 
leukapheresis.
Waivers to the protocol will not be granted during the conduct of this trial under any 
circumstances.
Safety laboratory analyses and all assessments will be performed locally. Screening laboratory 
values must demonstrate subject eligibility, but may be repeated within the screening window if 
necessary.
The following assessments are to be performed at screening as specified in the Table of Events 
(see Section 5), after informed consent has been obtained:

Assess eligibility per inclusion/exclusion criteria. All inclusion/exclusion criteria 
must be met in order for subjects to enroll in the study
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
Obtain medical history, including: disease diagnosis and history, HSCT history, 
chemotherapy, radiation and surgical history, and history of prior gene therapy. May 
include history of toxicities related to prior treatments and allergies 

Complete physical examination, including height, weight, vital signs (see 
Section 6.4.2), oxygen saturation via pulse oximetry and GVHD assessment (if 
applicable)

Routine neurologic examination 

ECOG performance status assessment and International Prognostic Index (IPI) status

MUGA scan or cardiac ECHO (performed within 4 weeks of leukapheresis) for 
LVEF

12-lead electrocardiogram (ECG) 

Collection of peripheral blood samples for clinical laboratory evaluations:

Chemistry 

Troponin-T or I (Arms B and E) and brain natriuretic peptide (BNP) (Arm B)
Subjects who are found at Screening to have baseline troponin-T > ULN or BNP 
> 100 pg/mL must have baseline evaluation by a cardiologist during Screening to 
optimize cardioprotective therapy.

Hematology 

Coagulation

Inflammatory markers

Thyroid function tests (Arms A and E)

Immunoglobulins

Viral serology 
Note: Subjects with positive hepatitis B surface antibody (HBsAb) but with negative hepatitis B 
core antibody (HBcAb) and hepatitis B surface antigen (HBsAg) or subjects with HBsAg, 
HBcAb and HBsAg negative are eligible for the study.

Serum ß-HCG pregnancy test on women of child-bearing potential 

Determination of creatinine clearance (by Cockcroft-Gault – see Appendix I)

Pregnancy prevention counselling (Arms B, C and F)
 
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
Urinalysis

Lumbar puncture or Ommaya reservoir tap for CSF assessment if CNS involvement 
suspected

Only for subjects with prior allogeneic HSCT:

HLA typing

Donor chimerism

If radiographic scans performed since the last anticancer treatment are not available to 
confirm the presence of PET-positive lymphoma, the Investigator should confirm the 
presence of lymphoma by clinical assessment or by a new PET scan 

Collection of tissue from latest archived tumor biopsy (block or slides) for tumor 
evaluation. If archival sample is before most recent relapse or no or insufficient 
archival sample is available, a new tumor biopsy is required. In case sufficient tumor 
biopsy material is not obtained during screening for Arms A, B and C, tumor biopsy 
may be performed prior to LD chemotherapy.

Bone marrow aspirate and biopsy (archival bone marrow biopsy is allowed if 
performed after last therapy and sufficient archival sample is available)

Record AEs, associated concomitant medications and procedures related to protocol-
mandated procedures. Any clinically significant conditions/events unrelated to study 
procedures should be reported as described in the CRF completion guidelines 
(CCGs).

Administration of European Quality of Life-5 Dimensions health state classifier to 5 
Levels (EQ-5D-5L) and European Organisation for Research and Treatment of 
Cancer-Quality of Life C30 (EORTC-QLQ-C30) questionnaires (Phase 2 only)

6.1.2.
Leukapheresis (Approximately 4 Weeks Prior to JCAR017 Administration)
Following enrollment on the study, subjects on Arm D subcohort A will start ibrutinib a 
minimum of 5 days prior to leukapheresis (see Section 3.1.6). 
Following enrollment on the study, a leukapheresis collection will be performed on each subject 
to obtain a sufficient quantity of peripheral blood mononuclear cells (PBMCs) for the production 
of the JCAR017 investigational product. Prior to leukapheresis, appropriate protocol mandated
washout periods are to be followed (see Table 22).
Should a technical issue arise during the procedure or in the processing of the product such that it 
cannot be used for JCAR017 administration, the subject may have a second collection procedure 
performed. Subjects must continue to meet eligibility requirements for repeat leukapheresis. 
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Table 22:
Washout Periods Prior to Leukapheresis (Continued)
Treatment
Washout
Oral chemotherapeutic agents (eg, lenalidomide 
and ibrutinib)a
3 half-lives
Radiation therapy
Radiation, multiple lesions
6 weeks
Radiation, single lesion, if additional non-
irradiated PET-positive lesions are present
2 weeks
a Subjects on Arm D are expected to continue ibrutinib.
6.1.3.
Pre-Lymphodepletion Evaluation
The following assessments are to be done as close as possible to the start of the lymphodepleting 
chemotherapy prior to any study treatment as specified in the Table of Events (see Table 21). 
In addition, for subjects who receive chemotherapy for disease control (see Section 8.1.1) while 
JCAR017 is being manufactured, the assessments must be performed after completion of the 
chemotherapy:

Assess/ confirm eligibility per inclusion/exclusion criteria:

PET positive disease

Adequate bone marrow function to receive LD chemotherapy as assessed by the 
investigator

Adequate organ function (as defined in Section 4.2)

No uncontrolled bacterial, viral or fungal infection 
In case of suspected infection, subject should be treated and LD chemotherapy postponed until 
the active infection has resolved.

Complete physical examination, including weight, and vital signs (see Section 6.4.2), 
oxygen saturation via pulse oximetry and GVHD assessment (if applicable). 

Routine neurologic examination

12-lead ECG

Collection of peripheral blood samples for clinical laboratory evaluations:

Chemistry 

Hematology 

Coagulation

Inflammatory markers
 
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
Computed tomography (CT)/ magnetic resonance imaging (MRI) of chest, neck, 
abdomen, and pelvis, and PET scan (recommended within 14 days of start of 
lymphodepleting chemotherapy and must be done within 6 weeks of the start of 
lymphodepleting chemotherapy). 

Collection of tissue for tumor evaluation for subjects for whom there was no 
screening biopsy performed, insufficient adequate biopsy material is available, or 
intervening treatment for disease control was received

Record all AEs, associated concomitant medications and procedures related to 
protocol-mandated procedures

Administration of EQ-5D-5L and EORTC-QLQ-C30 questionnaires (Phase 2, 
 

6.2.
Treatment Period
6.2.1.
Lymphodepleting Chemotherapy 
Subjects enrolled on Arm D should stop ibrutinib a minimum of 24 hours prior to the first dose 
of LD chemotherapy. Ibrutinib should be restarted the day after the last dose of LD
chemotherapy. In addition, ibrutinib may be interrupted for invasive procedures per institutional 
standards.
Upon notification from the Sponsor that JCAR017 will be available, LD chemotherapy should be 
initiated so as to be completed 2 to 7 days prior to JCAR017 infusion. For details on LD 
chemotherapy refer to Section 7.2.1.
The following assessments are to be performed on each day before administration of 
lymphodepleting chemotherapy: 

Inclusion/Exclusion criteria assessment: Subjects must be evaluated for evidence of 
active infections prior to the LD chemotherapy to be started. In case of suspected 
infection, subject should be treated accordingly and LD chemotherapy postponed 
until the active infection has resolved. Subjects with rapid deterioration or rapid 
disease progression should not start LD chemotherapy. In the event that a subject 
experiences any of the above, the Sponsor must be contacted and discussion 
regarding delay of treatment must occur.

Vital signs and pulse oximetry

ECOG performance status assessment (only once within 24 hours prior to start of LD 
chemotherapy)

Collection of peripheral blood samples for clinical laboratory evaluations:

Chemistry 
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
Hematology 

Creatinine clearance (CrCl) (by Cockcroft-Gault) (only once within 24 hours prior 
to start of LD chemotherapy – see Appendix I). If CrCl is below the acceptable 
level, direct measurement of renal function may be performed (eg, by 24 hr urine 
collection).

Serum ß-hCG pregnancy test on women of child-bearing potential (only on first 
day, prior to start of LD chemotherapy)

Pregnancy prevention counselling (Arm C and F)

Record all AEs, concomitant medications and procedures

Subjects on Arm D will restart ibrutinib on the day after the last dose of LD chemotherapy as 
described in Section 3.1.6.
6.2.2.
Day 1 (JCAR017 Administration)
Subjects who do not have adequate social support (a full-time caregiver) outside of the hospital 
or do not have reliable transportation to the clinic for scheduled evaluations or emergencies post 
therapy should be considered for hospitalization for the first 14 days of treatment. Subjects with 
high tumor burden are at higher risk of developing CRS and NT.
Subjects on Arm C subcohorts C, C+1 and C-1 will start CC-220 on Day 1 approximately 
2 hours after JCAR017 infusion and once the subject is clinically stable, as described in 
Section 3.1.5.
Subjects on Arm D will take ibrutinib on Day 1 approximately 2 hours after JCAR017 infusion 
and once the subject is clinically stable, as described in Section 3.1.6.
Subjects on Arm F subcohort B will start CC-99282 on Day 1 approximately 2 hours after 
JCAR017 infusion and once the subject is clinically stable, as described in Section 3.1.8.
In case the first dose of the combination agent is not given on the expected date (Day 1 for Arm 
C subcohorts C, C+1, C-1 or Arm D) but within the allowed time window (see Sections 3.1.9.3
and 3.1.9.4), subsequent visit dates should be rescheduled considering the same interval as in the 
original schedule.
The following assessments are to be performed prior to the JCAR017 infusion and combination 
agent (if applicable): 

Inclusion/Exclusion criteria assessment: Subjects should not experience a significant 
worsening in clinical status compared to initial eligibility criteria and/or rapid disease 
progression that would, in the opinion of the treating physician, increase the risk of 
adverse events associated with JCAR017 infusion. Subjects who meet at least one of 
the following criteria on the day of scheduled JCAR017 infusion should have 
JCAR017 administration delayed:
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-
Suspected or active systemic infection
-
Onset of fever ≥ 38°C/100.4°F, not related to underlying disease
-
Presence of progressive radiographic abnormalities on chest x-ray, or 
requirement for supplemental oxygen to keep saturation greater than 91% 
-
Cardiac arrhythmia not controlled with medical management
-
Hypotension requiring vasopressor support
-
New onset or worsening of other non-hematologic organ dysfunction 
≥Grade 3
-
Taking any of the prohibited medications as described in Section 8.2
Subjects with active infection must have JCAR017 infusion postponed until the active 
infection has resolved (subjects with suspected/active infection must have negative 
culture for at least 24 hours on appropriate antibiotics or negative rapid viral panel).
Subjects with organ toxicities may not receive JCAR017 until the organ toxicities have 
recovered to ≤ Grade 2. In case of delayed infusion, lymphodepleting chemotherapy may 
need to be repeated after discussion with the sponsor (see Section 7.2.1). In the event that 
a subject experiences any of the above, the Sponsor must be contacted and discussion 
regarding delay of treatment must occur.

Physical examination 

Weight 

Vital signs including pulse oximetry (measured approximately every 15 minutes 
starting from 15 minutes prior to the first IV administration until one hour after the 
last IV administration, and hourly for the next 2 hours [see Section 6.4.2]. If the 
subject’s vital signs are not stable 3 hours following the final IV administration, vital 
signs should be monitored as clinically indicated until stable).

ECOG performance status assessment 

Routine neurologic examination 

Mini-Mental Status Exam (MMSE) (see Appendix G). If subjects develop neurologic 
symptoms suspicious of and/or diagnosed as neurologic toxicity, subjects will have 
daily MMSE exams until resolution of symptoms, unless the subject is medically 
incapacitated and/or medically unable to complete the MMSE (see Section 6.4.5).

Record all AEs, concomitant medications and procedures

Collection of peripheral blood samples for clinical laboratory evaluations:

Chemistry

Hematology 

Coagulation 

Inflammatory markers 

Thyroid function tests (Arms A and E)
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
Inflammatory markers 

Pregnancy testing (Day 8 only, Arm C subcohorts B, B+1, B-1 and C, C+1, C-1, 
Arm E subcohorts A, B, C, A+1, B+1 and C+1, and Arm F)

Troponin T or I (Day 11 only, Arm E subcohorts A-1, B-1, C-1, A+2, B+2 and 
C+2)

Thyroid function test (Day 11 only: Arm E subcohorts A-1, B-1, C-1, A+2, B+2 
and C+2)

Pregnancy prevention counselling (Day 8 only, Arm C subcohorts B, B+1, B-1 and 
Arm F)

Thromboembolic event prophylaxis (Arm C subcohorts B, B+1, B-1 and C, C+1, C-1
and Arm F if needed) 

 
 
6.2.5.
Days 15 and 22 (± 2 days) 
Subjects on Arm C subcohorts A, A+1 and A-1 will start CC-220 on Day 15 as described in 
Section 3.1.5. In case the first dose of the combination agent is not given on the expected date 
(eg, Day 15 for subcohort A) but within the allowed time window, subsequent visit dates should 
be rescheduled considering the same interval as in the original schedule.
Subjects on Arm E subcohorts A-1, B-1, C-1, A+2, B+2 and C+2 will start nivolumab ± 
relatlimab on Day 15 as described in Section 3.1.7.
Subjects on Arm F subcohort C will start CC-99282 on Day 15 as described in Section 3.1.8. 
.
Arms A and B: The following assessments are to be performed at Days 15 and 22 (in case the 
first dose of the combination agent is administered on Day 22 then see Day 29 section 
[Section 6.2.6] for the assessments to be performed). However, for subjects receiving the 
combination agent post-JCAR017, Day 22 assessments should be performed if combination 
agent is given on Day 29. In case combination agent is given earlier than Day 29 (within the 
allowed time window), Day 29 assessments must be performed prior to start of the combination 
agent (eg, if combination agent is started on Day 22, Day 29 assessments must be performed 
prior to the start of the combination agent). The next regular visit will be Day 29. At this visit, 
only assessments scheduled for Day 36 should be performed. After that, the next subsequent 
protocol visits are to be performed. 
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
Vital signs and pulse oximetry

ECOG performance status assessment

Physical examination 

Routine neurologic examination 

MMSE (Day 15 only, see Appendix G and Section 6.4.5)

Record all AEs, concomitant medications and procedures

Collection of peripheral blood samples for clinical laboratory evaluations:

Chemistry 

Hematology 

Coagulation 

Inflammatory markers 

Thyroid function tests (Day 15: Arm A; Day 22: Arm E subcohorts A, B, C)

Troponin T or I (Day 22, Arm E subcohorts A, B, C)

Immunoglobulins 

Pregnancy testing (within 10 to 14 days prior to the start of CC-122) (Arm B) (Day 
22)

Pregnancy testing (Arm C and Arm F; Day 15 only Arm E subcohort A-1, B-1, C-1 
and A+2, B+2, and C+2)

Pregnancy prevention counselling (Day 15 only, Arm C subcohorts A, A+1, A-1, 
Arm E subcohorts A-1, B-1, C-1, A+2, B+2 and C+2, and Arm F)

Thromboembolic event prophylaxis (Arm C and Arm F is needed) 
 
 

6.2.6.
Day 29 (± 7 days) 
Subjects who do not have adequate social support (a full-time caregiver) outside of the hospital 
or do not have reliable transportation to the clinic for scheduled evaluations or emergencies post 
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therapy should be considered for hospitalization for the first 14 days of treatment. Subjects with 
high tumor burden are at higher risk of developing CRS and NT.
The following assessments are to be performed at Day 29. 
Arms A and B only: 
The assessments described below are to be performed at the above mentioned dates for 
subjects receiving the combination agent post-JCAR017 considering that the combination 
agent is started on the scheduled day (Day 29). If the first dose of the combination agent is 
given earlier or later than scheduled (within the allowed window), the following assessments 
should be shifted by the same number of days. In case the first dose of the combination agent 
is not given on Day 29 but within the allowed time window, the next dose/visit dates should 
be rescheduled accordingly: in case the combination agent is started on Day 22, the next 
dose/visit date would be 7 days after (Day 29), and subsequent dose/visit dates would be 
scheduled: 7 days later (Day 36), 2 weeks later (Day 50) and 4 weeks later (Day 78). For 
subjects who have only received JCAR017 and will not receive the combination agent due to 
any reason, the next visit will be on Day 57.
The following assessments are to be performed prior to the dose of combination agent, if 
scheduled for that day:

Physical examination 

Vital signs and pulse oximetry

Weight (Arm B and Arm C)

ECOG performance status assessment 

12-lead electrocardiogram (ECG) (Arm B)

Pregnancy testing (within 24 hours prior to the (re)start of CC-122 or CC-220) (Arms
B, C and F)

Routine neurologic examination 

Tumor biopsy (for subjects not in CR)

Bone marrow biopsy and aspirate (only for subjects with bone marrow involvement at 
Screening)

MMSE (see Appendix G and Section 6.4.5) 

Administration of EQ-5D-5L and EORTC-QLQ-C30 questionnaires (Phase 2, 


Record all AEs, concomitant medications and procedures 

Response evaluation by CT and PET scan 

Collection of peripheral blood samples for clinical laboratory evaluations:
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
Chemistry 

Troponin-T and BNP (Arm B; Arm E subcohorts A-1, B-1, C-1, A+2, B+2 and 
C+2)

Hematology 

Coagulation 

Inflammatory markers 

Thyroid function tests (Arm A, Arm E subcohorts A-1, B-1, C-1)

Immunoglobulins 

Determination of creatinine clearance (by Cockcroft-Gault – see Appendix I) 
(Arm B)

Pregnancy prevention counselling (Arm B, Arm C, Arm F)

Thromboembolic event prophylaxis (Arm C); if needed (Arm B and Arm F) 
 
 
Combination agent will be started or restarted as per Table 3 for subjects in Arm A, Table 4 for 
subjects in Arm B, or Table 5 for Arm C. 
6.2.7.
Days 30, 31, 32 and 39 (Arm B)
The assessments described below are to be performed at the above mentioned dates for subjects 
receiving the combination agent post-JCAR017 considering that the combination agent is started 
on Day 29. In case the first dose of the combination agent is given earlier or later than Day 29
(within the allowed window), the following assessments should be performed before subsequent 
doses of the combination agent.
The following assessments are to be performed:

Vital signs and pulse oximetry

Routine neurologic examination 

Physical examination 

MMSE (Day 32 only, see Appendix G and Section 6.4.5)

Record all AEs, concomitant medications and procedures
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
Collection of peripheral blood samples for clinical laboratory evaluations:

Chemistry 

Hematology 

Coagulation 

Inflammatory markers 

12-lead ECG, Troponin-T and BNP, MUGA/ECHO: if clinically indicated 
 

6.2.8.
Days 36, 43, and 57 (± 2 days)
Arm A and Arm B only: the assessments described below are to be performed at the above 
mentioned dates for subjects receiving the combination agent post-JCAR017 considering that the 
combination agent is started on Day 29 the first dose of the combination agent is given earlier or 
later than Day 29 (within the allowed window), the following assessments should be performed 
before subsequent doses of the combination agent. 
For subjects who have only received JCAR017 and will not receive the combination agent due to 
any reason, the next visit will be on Day 85.
For subject in Arm A - Cohort 1A-1, some of the following assessments are also to be performed 
on Days 50 and 71 (see Table 10 for the details).
For subjects in Arm A - Cohort 1A-2, please refer to Table 11 for the details of the assessments 
to be performed at the above mentioned visits.
Arm C: Day 36 visit is to be performed for Arm C subcohorts A and B while Day 43 is to be 
performed for Arm C subcohorts B and C.
Arm D: only Day 57 visit is required.
Arm E: Day 36 visit is to be performed for subcohorts A, B, C, A+1, B+1, C+1; Day 43 visit 
performed for subcohorts A-1, B-1, C-1, A+2, B+2, C+2; Day 57 visit is performed for all 
subcohorts.
The following assessments are to be performed, prior to the dose of combination agent, if 
scheduled for that day:

Physical examination 

Vital signs and pulse oximetry

ECOG performance status assessment 

Weight (Arm B and Arm C) (Day 57)
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
Routine neurologic examination 

Bone marrow biopsy and aspirate (if clinically indicated)

MMSE (see Appendix G and Section 6.4.5) 

Administration of EQ-5D-5L and EORTC-QLQ-C30 questionnaires (Day 57) (Phase 
2, 

 

Record all AEs, concomitant medications and procedures

Collection of peripheral blood samples for clinical laboratory evaluations:

Chemistry 

Hematology 

Coagulation 

Inflammatory markers 

Thyroid function tests (Arm A; Day 36: Arm E subcohorts A, B, C, A+1, B+1, 
C+1; Day 43 Arm E subcohorts A-1, B-1, C-1; Day 57 Arm E all subcohorts)

Troponin T or I (Day 36: Arm E subcohorts A, B, C, A+1, B+1 and C+1; Day 43 
Arm E subcohorts A-1, B-1, C-1, A+2, B+2, C+2; Day 57 Arm E all subcohorts)

Immunoglobulins (Day 57 for Arms B, C, D, E and F; Day 36: Arm E subcohorts 
A, B, C, A+1, B+1, C+1; Day 43 Arm E subcohorts A-1, B-1, C-1, A+2, B+2, 
C+2)

Pregnancy testing (Arm B and Arm C; Day 36 Arm E subcohorts A, B, C, 1A+1, 
1B+1, 1C+1; Day 43 Arm E subcohorts A-1, B-1, C-1, A+2, B+2, C+2; Day 57 Arm 
E all subcohorts and Arm F)

Pregnancy prevention counselling (Day 43 Arm B) (Day 57 Arm B, Arm C and Arm 
F)

Thromboembolic event prophylaxis (Arm C); if needed (Arm B and Arm F if needed)

12-lead ECG, Troponin-T and BNP, MUGA/ECHO: if clinically indicated (Arm B)
 
 
 
 
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6.2.9.
Days 50, 64, 71 and 78 (± 2 days) (Arm B)
The assessments described below are to be performed at the above mentioned dates for subjects 
receiving the combination agent post-JCAR017 considering that the combination agent is started 
on the scheduled day (Day 29).
If the first dose of the combination agent is given earlier or later than scheduled (within the 
allowed window), the following assessments should be shifted by the same number of days.
For subjects who have only received JCAR017 and will not receive the combination agent due to 
any reason, the next visit will be on Day 85.
The following assessments are to be performed, prior to the dose of combination agent, if 
scheduled for that day:

Physical examination 

Vital signs and pulse oximetry

VTE prophylaxis if needed; 12-lead ECG, Troponin-T and BNP, MUGA/ECHO: if 
clinically indicated 

 

Record all AEs, concomitant medications and procedures

Collection of peripheral blood samples for clinical laboratory evaluations:

Chemistry 

Hematology 

Inflammatory markers 

Pregnancy testing (Day 50)
6.2.10.
Day 85 (± 7 days)
The assessments described below are to be performed at the above mentioned dates for subjects 
receiving the combination agent post-JCAR017 considering that the combination agent is started 
on the scheduled day (Day 29). If the first dose of the combination agent is given earlier or later 
than scheduled (within the allowed window), the following assessments should be shifted by the 
same number of days. 
Arms A and C: If the combination agent is continued beyond Day 85, see Section 6.3.1.
For subjects who have only received JCAR017 and will not receive the combination agent due to 
any reason, the next visit will be on Day 180.
The following assessments are to be performed, prior to the dose of combination agent, if 
scheduled for that day:

Physical examination 

Vital signs

ECOG performance status assessment 
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
Weight (Arm B and Arm C)

Routine neurologic examination 

Bone marrow biopsy and aspirate (if clinically indicated)

MMSE (see Appendix G and Section 6.4.5) 

Administration of EQ-5D-5L and EORTC-QLQ-C30 questionnaires (Phase 2, 

 

Record all AEs, concomitant medications and procedures

PET scan (not required for subjects in CR, subjects who have progressed, or after 
institution of additional anticancer treatment. A PET scan should be performed to 
verify PD) 

CT/MRI scan (not required after PD or after institution of additional anticancer
treatment)

Collection of peripheral blood samples for clinical laboratory evaluations:

Chemistry 

Hematology 

Thyroid function tests (Arm A and Arm E)

Inflammatory markers 

Immunoglobulins (Not required if B-cell recovery documented without recent 
administration of intravenous immunoglobulin [IVIG]) 

Serum ß-HCG pregnancy test on women of child-bearing potential 

Troponin T or I (Arm E all subcohorts)

Pregnancy prevention counselling (Arm B, Arm C and Arm F)

Thromboembolic event prophylaxis (Arm C); if needed (Arm B)

12-lead ECG, Troponin-T and BNP, MUGA/ECHO: if clinically indicated (Arm B)
 
 
 
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6.2.11.
Day 113 (± 7 days) (Arm B)
The following assessments are to be performed:

Physical examination 

Vital signs

Weight

ECOG performance status assessment

Collection of peripheral blood samples for clinical laboratory evaluations:

Chemistry 

Hematology 

Inflammatory markers 

Bone marrow biopsy and aspirate (if clinically indicated)

Pregnancy testing 

Pregnancy prevention counselling

VTE prophylaxis if needed

12-lead ECG, Troponin-T and BNP, MUGA/ECHO: if clinically indicated

 

Record all AEs, concomitant medications and procedures
6.2.12.
Days 141 and 169 (± 7 days) (Arm B)
The following assessments are to be performed:

Physical examination (Day 141)

Vital signs

Weight (Day 141)

ECOG performance status assessment (Day 141)

Collection of peripheral blood samples for clinical laboratory evaluations:

Chemistry 

Hematology 

Inflammatory markers 

Pregnancy testing

Pregnancy prevention counselling

VTE prophylaxis if needed; 
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
12-lead ECG, Troponin-T and BNP, MUGA/ECHO: if clinically indicated 

 

Record all AEs, concomitant medications and procedures
6.2.13.
Day 180 (± 7 days) (Arm B)
Note: Arm A, C and D Day 180 visits are described in Section 6.3 since they occur after the end 
of treatment.
The following assessments are to be performed:

Vital signs

Weight

Collection of peripheral blood samples for clinical laboratory evaluations:

Chemistry 

Hematology 

Inflammatory markers 
 
 

VTE prophylaxis if needed

12-lead ECG, Troponin-T and BNP, MUGA/ECHO: if clinically indicated

 

Record all AEs, concomitant medications and procedures
6.3.
Post-Treatment Period
6.3.1.
Follow-up
All subjects who received any dose of JCAR017, including subjects who withdraw from 
treatment early and those with progressive disease, should complete the post-treatment follow-up 
visits at approximately Days 113 (Arm C only), 180 (except Arm B), 208 (Arm B), 270 (± 14 
days), 365, 545, and 730 (± 30 days), Months 6 (except Arm B), 7 (Arm B), 9, 12, 18, and 24 or 
end of study [EOS]) after the JCAR017 infusion for disease status and survival. The following 
assessments will be performed in subjects who have not received subsequent anticancer 
treatment: 
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6.3.1.2.
Specific Follow-up for CC-122 After Day 180 in Arm B
In case treatment with CC-122 is continued beyond Day 180 (see Section 3.1.4 for conditions 
where this could occur), the following assessments are to be performed: 
Every 4 weeks: 

Weight

Collection of peripheral blood samples for clinical laboratory evaluations:

Hematology 

Chemistry 

Pregnancy testing 

12-lead ECG, Troponin-T and BNP, MUGA/ECHO: if clinically indicated 
In addition, a serum ß-HCG pregnancy test on women of child-bearing potential should be 
performed 28 days after the last dose of CC-122. Deep vein thrombosis prophylaxis should also 
be performed if needed.
Record all AEs, associated con meds and procedures from start of LD chemo or start of 
combination agent whichever occurs first until 3 months after JCAR017 or 28 days after last 
dose of CC-122, whichever occurs later. After this time, record only AEs related to JCAR017 
and/or lymphodepleting chemotherapy or combination agents and associated concomitant
medications/procedures.
6.3.1.3.
Specific Follow-up for CC-220 After Day 85 in Arm C
In case treatment with CC-220 is continued beyond Day 85 (see Section 3.1.5 for conditions 
where this could occur), the following assessments are to be performed in addition to the 
follow-up schedule (see also Table 14).
After stopping CC-220, the subsequent 2 visits in Table 14 covering the below assessments must 
be performed before returning to the standard follow-up schedule in Section 6.3.1.
Every 4 weeks: 

ECOG

Physical examination

Vital signs

Weight

Pregnancy testing and prevention counselling 
A serum ß-HCG pregnancy test on women of child-bearing potential should be performed 28 
days after the last dose of CC-220.

Collection of peripheral blood samples for clinical laboratory evaluations:

Hematology 

Chemistry 
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6.3.5.
Early Withdrawal 
If a subject voluntarily withdraws prematurely from the study, a visit will be scheduled as soon 
as possible, and all of the assessments listed for the Day 730 (24 months [EOS]) visit will be 
performed. 
6.3.6.
New Malignancies Follow-up Period
New malignancies will be monitored as events of interest and must be reported as serious 
adverse events regardless of the treatment arm and cohort the subject was in. This includes any 
new malignancies, regardless of causal relationship to IP(s), occurring throughout the subject’s 
entire participation in the study. If a subject develops a new malignancy, the Sponsor will request 
a tumor sample (refer to JCAR017-BCM-002 laboratory manual) and blood samples (see also 
Section 6.4.10 and Section 6.4.11).
6.3.7.
Survival Follow-up
All subjects, except screen failures, will be followed for survival every 3 months until last 
subject last visit. Additional survival follow-up information will be collected in the context of the 
LTFU protocol.
6.3.8.
Long-Term Follow-up 
Because this protocol involves gene transfer, long-term follow-up for lentiviral vector safety, 
disease status, and long-term survival will continue on this protocol until 24 months after last 
dose of JCAR017, regardless of disease status, and under a separate LTFU protocol thereafter for 
up to 15 years after the JCAR017 infusion as per health authority regulatory guidelines (Food 
and Drug Administration [FDA], 2006; FDA, 2018; European Medicines Agency [EMA], 2009). 
All subjects who either complete the primary follow-up period specified in this protocol or who 
prematurely withdraw after JCAR017 infusion will be asked to enroll in the LTFU protocol at 
the EOS visit or at the time of withdrawal, respectively. A separate informed consent form will 
be provided for the LTFU protocol. Subjects who do not consent to participate in the LTFU 
protocol will be followed for survival through public record. 
6.4.
Safety Assessments
6.4.1.
Physical Examination
A physical examination should include assessments of the following body parts/systems: 
abdomen, extremities, heart, lungs, and neurological. In addition, symptom-directed exams 
should be performed.
6.4.2.
Vital Signs
Vital signs include temperature, respiratory rate, heart rate, blood pressure. On the day of 
JCAR017, durvalumab and relatlimab/nivolumab administration, special monitoring is to be 
performed, refer respectively to Section 7.2.2.4, Section 7.2.4.3 and Section 7.2.8 for details.
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6.4.3.
Pulse Oximetry
SaO2 will be assessed by pulse oximetry as per the Tables of Events (See Table 21).
6.4.4.
Height and Weight
Height in centimeters (cm) or inches (in) and body weight to the nearest kilogram (kg) or pound 
(lb) in indoor clothing, but without shoes will be measured according to the Tables of Events 
(See Table 21). For subjects receiving CC-122 or CC-220, weight is to be assessed every 4 
weeks.
6.4.5.
Routine Neurologic and Mini Mental State Examinations
A routine neurologic examination should include, at minimum, a physical exam to assess cranial 
nerves, motor and sensory skills, coordination and balance, and the Mini Mental State 
Examination (MMSE; see Appendix G). The MMSE may be administered by an appropriately 
trained provider (ie, physician, nurse); a neurologist is not required. Efforts should be made to 
have the same provider perform the MMSE on a given subject to maintain consistency of 
assessment. If subjects develop neurologic symptoms suspicious of and/or diagnosed as 
neurologic toxicity, subjects will have daily MMSE exams until resolution of symptoms, unless 
the subject is medically incapacitated and/or medically unable to complete the MMSE.
6.4.6.
Cerebrospinal Fluid Assessment
Cerebrospinal fluid (CSF) assessment and CNS imaging should be performed if CNS 
involvement is suspected at screening or at any time during the study as clinically indicated (eg, 
if new CNS symptoms occur, or if clinical signs or suspicion of CNS lymphoma exist). CSF will 
be analyzed for cell count and differential cytology, and for the presence of JCAR017 (see the 
JCAR017-BCM-002 laboratory manual for instructions on sending a sample for JCAR017 
testing). CSF cultures (bacterial, fungal, viral) should be performed as clinically indicated for 
suspicion of infection.
6.4.7.
ECOG Performance Status
ECOG performance status (see Appendix B) will be used to evaluate subject eligibility at 
screening and will be assessed throughout the study at time points specified in the Tables of 
Events (See Table 21).
6.4.8.
Multi-gated Acquisition Scan / Echocardiogram
An assessment of LVEF will be performed by ECHO or MUGA to assess the cardiac function of 
the subject and to confirm study eligibility.
6.4.9.
Electrocardiogram 
A standard 12-lead ECG should be obtained. ECG tracings should be labelled with the study 
number, subject number, date, and Investigator’s signature, and kept in the source documents at 
the study site.
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6.4.12.
Clinical Laboratory Evaluations
Screening and other laboratory evaluations (see Appendix H) will be performed according to the 
Tables of Events (See Table 21). Additional assessments should be performed between 
scheduled study visits as clinically required in order to diagnose and monitor AEs/SAEs or 
expected events.
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6.5.
Efficacy Assessment 
Efficacy response will be assessed according to the “Recommendations for Initial Evaluation, 
Staging, and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma: The Lugano 
Classification” (Cheson, 2014) based on radiographic tumor assessments. Subjects will have 
radiographic disease assessment by PET and/or CT or MRI scans (minimum of chest, neck, 
abdomen, and pelvis) at baseline and approximately 1, 3, 6, 9, 12, 18 and 24 months following 
treatment or until disease progression. Efficacy assessment will be performed by PET/CT until 
Month 3 and afterwards, once PET is negative, only CT is required. Starting from protocol 
Amendment 4 please refer to the Celgene Lugano Classification guidelines (Appendix F).
6.5.1.
Potential Pseudoprogression 
If a subject demonstrates early tumor progression (defined as occurring prior to/at 3 months after 
JCAR017 or start of combination agent, whichever occurs last), the investigator is responsible 
for evaluating whether the subject is experiencing a possible pseudoprogression (ie, tumor flare 
(see Section 10.6.4.3), which is local inflammatory reaction indicating early tumor response at 
sites of disease such as lymph nodes) which has been described in subjects treated with 
checkpoint inhibitors (Cheson, 2016).
6.6.
Pharmacokinetics 
6.6.1.
Pharmacokinetics of JCAR017
Assessment of JCAR017 PK will be determined by qPCR to detect the JCAR017 transgene and/ 
or by flow cytometry to enumerate JCAR017 cells. Peripheral blood and CSF will be collected as 
indicated in the Tables of Events (See Table 21).
Detailed information regarding the collection, handling, and shipment of PK assessment samples 
is provided in the JCAR017-BCM-002 laboratory manual.
6.6.2.
Pharmacokinetics of Durvalumab
PK sampling will be performed for all subjects taking JCAR017 in combination with 
durvalumab (Arm A). The sampling time points will be as follows:

Post-expansion cohort: pre-infusion of durvalumab (-30 to -5 minutes prior to dose) 
and end of infusion (EOI [+ up to 5 mins]) on each infusion day of durvalumab (see 
Section 3.1.3 and Table 3).

If treatment with durvalumab is continued beyond Day 85, PK sampling will be done 
pre-infusion of durvalumab (-30 to -5 minutes prior to dose) and EOI (+ up to 5 mins) 
on each infusion day of durvalumab.
6.6.3.
Pharmacokinetics of CC-122
PK sampling will be performed for all subjects taking JCAR017 in combination with CC-122 
(Arm B). The sampling time points will be as follows:
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
Post-expansion cohort: pre-dose of CC-122 (-30 to -5 minutes prior to dose), 1.5 
hours (± 10 min) and 3 hours post-dose (± 10 min) on Day 29 and Day 36 (see 
Section 3.1.4 and Table 4) and only pre-dose on Days 85 and 180.
6.6.4.
Pharmacokinetics of CC-220
PK sampling will be performed for all subjects taking JCAR017 in combination with CC-220 
(Arm C). 
Pharmacokinetic blood samples will be collected in subjects pre-dose of CC-220 (22 to 26 hours 
after the preceding dose and prior to the next dose), 2 hours (± 10 min) and 4 hours post-dose 
(± 10 min) on Day 36 (see Section 3.1.5 and Table 5) and only pre-dose (or 22 to 26 hours after 
the preceding dose) on Days 22 and 85.
The sampling will allow evaluation of plasma CC-220, and as appropriate, the pharmacologically 
active metabolite, M12, in an exploratory manner. 
6.6.5.
Pharmacokinetics of Ibrutinib
PK sampling will be performed for all subjects taking JCAR017 in combination with ibrutinib 
(Arm D). The sampling time points will be as follows:

Pre-dose of ibrutinib (-4 hours to -5 minutes prior to ibrutinib dose) on Days 1, 15, 
29, and 85
6.6.6.
Pharmacokinetics of Nivolumab and Relatlimab
PK sampling will be performed for all subjects in Arm E. The sampling time points will be as 
follows:
Table 23:
Pharmacokinetic Sampling for Arm E
Cohort
Sub-cohort
Nivolumab ± 
Relatlimab Schedule
Study Day
8
15
22
29
36
43
57
85
Cohort 
1
Post-
infusion
A, B, C
Day 8, 22, 36, 57, 85 
pre/post
-
pre
-
pre
-
pre/post
pre
A+1, B+1, C+1
Day 8, 36, 57, 85
pre/post
-
x
-
pre
-
pre
pre
A-1, B-1, C-1
Day 15, 29, 43, 57, 85
-
pre/post
-
pre
-
pre
pre/post
pre
A+2, B+2, C+2
Day 15, 57, 85
-
pre/post
-
x
-
-
pre
pre
Study Day visit windows are given in Section 5.5.
For subjects receiving relatlimab in combination with nivolumab, post infusion samples for both nivolumab and 
relatlimab if given should be collected after the end of infusion (preferably within 2 minutes prior to the end of 
infusion). If the end of infusion is delayed to beyond the nominal infusion duration, the collection of this sample 
should also be delayed accordingly. Post-infusion samples may not be collected from the same intravenous access as 
drug was administered; refer to the Laboratory Procedures Manual for additional restrictions.
Peripheral blood samples will also be taken pre-dose at the above timepoints for immunogenicity to nivolumab / 
relatlimab.
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6.6.7.
Pharmacokinetics of CC-99282
PK and PD sampling will be performed for all subjects taking JCAR017 in combination with 
CC-99282 (Arm F). The sampling timepoints will be as follows: 
Table 24:
Pharmacokinetic Sampling for Arm F
Cohort 
Sub-
cohort
CC-99282 
Schedule
Study Day
1
2b
3c
8
9b
10c
15
22
29
Cohort 1 
Post-
Infusion
A
Day 8, Q7D
-
-
-
Pre-
dose, 
1, 2, 6 
hr  
x
x
x
-
-
B
Day 1, Q7D
Pre-
dose, 
1, 2, 6 
hr
x
x
x
-
-
-
-
-
Ca
Day 15, Q7D
-
-
-
-
-
-
Pre-
dose, 
1, 2, 6 
hr
x
-
D
Day 8, Q7D
-
-
-
Pre-
dose, 
1, 2, 6
hr
x
x
x
-
-
E
Day 8 Q14D
-
-
-
Pre-
dose, 
1, 2, 6
hr
x
x
x
-
-
F
Day 8 Q7D
-
-
-
Pre-
dose, 
1, 2, 6
hr
x
x
x
-
-
Abbreviations: hr = hour; Q7D = every 7 days
Study Day visit windows are given in Section 5.6.
a Subjects in subcohort C will be discharged at Day 15 and return to the clinic at Day 22.
b 24 hours after CC-99282 dose.
c 48 hours after CC-99282 dose.
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6.8.1.
EORTC QLQ-C30
The EORTC QLQ-C30 questionnaire will be used as a measure of health-related quality of life. 
The QLQ-C30 is composed of both multi-item scales and single item measures. These include 
five functional scales (physical, role, emotional, cognitive and social), three symptom scales 
(fatigue, nausea/vomiting, and pain), a global health status/health-related quality of life (HRQoL) 
scale, and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial 
difficulties). Each of the multi-item scales includes a different set of items – no item occurs in 
more than one scale.
The QLQ-C30 employs a week recall period for all items and a 4-point scale for the functional 
and symptom scales/items with response categories “Not at all”, “A little”, “Quite a bit” and 
“Very much”. The two items assessing global health status/ HRQoL utilize a 7-point scale 
ranging from 1(“Very Poor”) to 7 (“Excellent”) (Aaronson, 1993). 
6.8.2.
EQ-5D-5L
EQ-5D is a standardized measure of health status developed by the EuroQol Group in order to 
provide a simple, generic measure of health for clinical and economic appraisal. The EQ-5D-5L 
consists of the EQ-5D-5L descriptive system and the EQ visual analogue scale (EQ VAS). The 
descriptive system comprises dimensions (mobility, self-care, usual activities, pain/discomfort, 
anxiety/depression). Each dimension has 5 levels (no problems, slight problems, moderate 
problems, severe problems, extreme problems)
In 2005, a Task Force was established within the EuroQol Group to investigate methods to 
improve the instrument’s sensitivity and to reduce ceiling effects. After much discussion, the 
Task Force decided that there should be no change in the number of dimensions for a new 
version of EQ-5D.
However, previously published studies by EuroQol Group members showed that experimental 5-
level versions of EQ-5D could significantly increase reliability and sensitivity (discriminatory 
power) while maintaining feasibility and potentially reducing ceiling effects.
The EQ-5D-5L still consists of 2 pages – the EQ-5D-5L descriptive system (page 2) and the EQ 
Visual Analogue Scale (page 3). The descriptive system comprises the same 5 dimensions as the 
EQ-5D-3L (mobility, self-care, usual activities, pain/discomfort, anxiety/depression).
However, each dimension now has 5 levels: no problems, slight problems, moderate problems, 
severe problems, and extreme problems. The respondent is asked to indicate his/her health state 
by ticking (or placing a cross) in the box against the most appropriate statement in each of the 5 
dimensions. This decision results in a 1-digit number expressing the level selected for that 
dimension. The digits for 5 dimensions can be combined in a 5-digit number describing the 
respondent’s health state. It should be noted that the numerals 1-5 have no arithmetic properties 
and should not be used as a cardinal score.
The EuroQol Group had received feedback over the years that respondents sometimes found it 
difficult to draw a line from the box to the scale. It was also cumbersome for administrators to 
record their scores. The EQ-5D-5L now asks respondents to simply ‘mark an X on the scale to 
indicate how your health is TODAY’ and then to ‘write the number you marked on the scale in 
the box below’.
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This should make the task easier for both respondents and users (Herdman, 2011; EuroQol, 
1990). See Appendix K.
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7.
DESCRIPTION OF STUDY TREATMENTS
7.1.
Description of Investigational Product(s)
7.1.1.
JCAR017 (Lisocabtagene maraleucel; liso-cel)
See Section 1.2.1 for JCAR017 description.
See the JCAR017 Product Administration Manual for details of packaging and labeling, product 
request and shipment, product preparation and administration, and product disposal and 
destruction. 
7.1.2.
Durvalumab (Arm A)
See Section 1.2.2 for durvalumab description. 
7.1.3.
CC-122 (Arm B)
See Section 1.2.3 for CC-122 description.
7.1.4.
CC-220 (Arm C)
See Section 1.2.4 for CC-220 description.
7.1.5.
Ibrutinib (Arm D)
See Section 1.2.5 for ibrutinib description.
7.1.6.
Relatlimab (Arm E)
See Section 1.2.6 for relatlimab description.
7.1.7.
Nivolumab (Arm E)
See Section 1.2.7 for nivolumab description.
7.1.8.
CC-99282 (Arm F)
See Section 1.2.8 for CC-99282 description.
7.2.
Treatment Administration and Schedule
Subject eligibility criteria must be reconfirmed prior to starting lymphodepleting chemotherapy 
and subsequent treatment with JCAR017. 
7.2.1.
Lymphodepleting Chemotherapy
Lymphodepleting chemotherapy will be obtained locally according to local clinical study 
agreement and in accordance with local guidelines.
Subjects will be treated with fludarabine IV (30 mg/m2/day for 3 days) plus cyclophosphamide 
IV (300 mg/m2/day for 3 days) concurrently prior to treatment with JCAR017. Refer to the most 
recent package inserts for further details on administration of these agents.
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LD chemotherapy should be initiated so as to be completed 2 to 7 days before JCAR017 
administration. If side effects from the lymphodepleting chemotherapy occur, JCAR017 infusion 
may be delayed for up to 14 days after lymphodepleting chemotherapy upon discussion with the 
Sponsor. Delay of LD chemotherapy by more than 14 days requires discussion with the Sponsor;
delay of LD doses or JCAR017 may require some screening procedures and/or LD 
chemotherapy to be repeated. Refer to Section 6.2.1 for the assessments that will be performed 
on each day of lymphodepleting chemotherapy.
LD chemotherapy must only be given if the subject has adequate performance and adequate bone 
marrow function to receive LD chemotherapy as assessed by the Investigator. 
The recommended administration is as follows: 

The IV hydration is 1 L of balanced crystalloid (according to institutional guideline)
given at 500 mL/hr starting 2 hours prior to cyclophosphamide 

Fludarabine 30 mg/m2 IV over 30 minutes 

If creatinine clearance 60 to 70 mL/min: Reduce dose by 20% each daily dose of 
fludarabine

If creatinine clearance < 60 mL/min: Withhold dose, subject no longer eligible
Indirect calculation of creatinine clearance should be performed using the Cockcroft-
Gault formula (Appendix I). Direct measurement of creatinine clearance is also 
acceptable.

Cyclophosphamide 300 mg/m2 IV over 60 minutes 

Additional 1 L of balanced crystalloid (according to institutional guidelines) given at 
500 mL/hr 
Antiemetic therapy may be given prior to LD chemotherapy per institutional practice. Mesna 
may be used for subjects with a history of hemorrhagic cystitis per institutional practice.
7.2.2.
JCAR017 Treatment
7.2.2.1.
JCAR017 Dose and Schedule
JCAR017 will be infused at a dose of JCAR017 positive transduced viable T cells (CAR+ 
T cells) at 2 dose levels depending on cohort assignment. JCAR017 will be given on Day 1 (2 to 
7 days after completion of lymphodepleting chemotherapy). 

DL1 : 50 x 106 CAR+ T cells 

DL2 : 100 x 106 CAR+ T cells 
7.2.2.2.
JCAR017 Preparation and Cell Thawing
See the JCAR017-BCM-002 Product Administration Manual for details.
7.2.2.3.
JCAR017 Premedication
Subjects should be pre-medicated with 500 to 650 mg acetaminophen oral (PO) and 25 to 50 mg 
diphenhydramine hydrochloride (PO or IV) 30 to 60 minutes prior to JCAR017 infusion. In case 
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the diphenhydramine is not available in a country, it is acceptable to use another H1 
antihistamine.
These medications may be repeated every 6 hours as needed based on the Investigator’s 
assessment of symptoms. Pre-medication with steroids should be avoided.
7.2.2.4.
JCAR017 Administration
Each JCAR017 dose consists of CD4+ CAR+ T cells and CD8+ CAR+ T cells, administered 
separately via IV. The subject must be continuously monitored during each IV administration of 
JCAR017. Vital signs (temperature, respiratory rate, heart rate, blood pressure, and SaO2 by 
pulse oximetry) will be measured approximately every 15 minutes starting from 15 minutes prior 
to the first IV administration until one hour after the last IV administration, and hourly for the 
next 2 hours. If the subject’s vital signs are not stable 3 hours following the final IV 
administration, vital signs should be monitored as clinically indicated until stable.
See the JCAR017-BCM-002 Product Administration Manual for complete information.
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7.2.4.
Durvalumab Treatment 
Durvalumab will be administered as an IV infusion at the assigned dose. In Arm A Cohort 1, 
continued dosing at an approximately Q4W interval may be allowed after Day 85. Maximal total 
duration of treatment with durvalumab will be 12 months (see Section 3.1.2).
Guidelines for management of durvalumab-related toxicities are presented in Appendix C,
Appendix D and Appendix E. Any subject meeting any of the criteria for withholding therapy on 
the day of their scheduled durvalumab infusion will have the durvalumab infusion withheld until 
the abnormalities improve. 
7.2.4.1.
Durvalumab Drug Product 
Durvalumab (MEDI4736) will be supplied by Celgene in single use vials in single count cartons 
and labeled appropriately as investigational material for this study. Each 10R vial will be 
supplied as a vialed liquid solution containing 500 mg (nominal) of durvalumab at a
concentration of 50 mg/mL. Durvalumab should be stored in accordance with the product label.

Sites will supply IV infusion bags with dilution solution and infusion lines with 
appropriate filters. IV infusion bags of normal saline (0.9% [w/v] sodium chloride or 
5% [w/v] dextrose injection, 250 mL size). Saline or dextrose bags must be latex-free 
and can be made of polypropylene, polyethylene, polyolefin copolymers, or polyvinyl 
chloride. Infusion lines should contain a 0.2 to 0.22 μm in-line filter.
Since the compatibility of durvalumab with other IV medications and solutions than normal 
saline, is not known, the durvalumab solution should not be infused through an IV line in which 
other solutions or medications are being administered.
For additional information on preparation and storage, please refer to the Pharmacy Manual.
7.2.4.2.
Durvalumab Premedication
Subjects should be premedicated with 500 to 650 mg acetaminophen PO and 25 to 50 mg 
diphenhydramine hydrochloride (PO or IV) 30 to 60 minutes prior to durvalumab infusion. 
These medications may be repeated every 6 hours as needed based on the Investigator’s 
assessment of symptoms. Premedication with steroids should be avoided.
7.2.4.3.
Durvalumab Preparation and Administration 
The dose of durvalumab for administration must be prepared by the Investigator’s or site’s 
designated investigational product (IP) manager using aseptic technique. Total time from needle 
puncture of the vial to the start of administration should not exceed: 

24 hours at 2°C to 8°C (36°F to 46°F) 

4 hours at room temperature 
Durvalumab will be administered using an IV bag containing 0.9% (w/v) saline or 5% [w/v] 
dextrose, with a final in-bag concentration ranging from 0.15 mg/mL to 20 mg/mL, and 
delivered through an IV administration set with a 0.2 μm or 0.22 μm in-line filter. 
The IV bag size should be selected such that a final durvalumab in-bag concentration of 0.15 
mg/mL to 20 mg/mL is achieved. Infusions should be given over a period of 60 minutes.
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Note: Special monitoring requirements are associated with each infusion of durvalumab:

Subjects will have their temperature, blood pressure and pulse measured before, 
during and after the infusion at the following times (based on a 60-minute infusion):

At the beginning of the infusion (at 0 minutes)

At 30 minutes during the infusion (±5 minutes)

At the end of the infusion (at 60 minutes ±5 minutes)

In the 2-hour observation period post-infusion: every 30 minutes (±5 minutes) 
after the infusion (ie, 90, 120, 150, and 180 minutes from the start of the infusion)

If the infusion takes longer than 60 minutes, then temperature, blood pressure and 
pulse measurements should be collected every 30 minutes (± 5 minutes) and as 
described above or more frequently if clinically indicated.
7.2.4.4.
Durvalumab Dose Interruptions
Dose interruptions are permitted for appropriate management of AEs. Treatment may be 
interrupted or discontinued or infusion rate may be changed at the discretion of the investigator 
for severe infusion or allergic reactions, or other toxicities.
Dose modifications must be recorded in the Dose Administration CRF.
7.2.4.5.
Durvalumab Dose Modification Guidelines
Subjects will be evaluated for AEs at each visit with the National Cancer Institute CTCAE 
version 4.03 used as a guide for the grading of severity, with the exception of tumor lysis 
syndrome (Cairo, 2004) in Appendix L.
Dose modifications guidelines for immune mediated reactions (Haanen, 2017), non-immune-
mediated reactions and infusion-related reactions should be followed and are detailed 
respectively in Appendix C, Appendix D and Appendix E.
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7.2.7.
Ibrutinib Treatment
7.2.7.1.
Ibrutinib Drug Product
For Phase 1 ibrutinib (IMBRUVICA®; 140-mg formulated capsules) will be sourced locally by 
the clinical site responsible for use in this trial and stored as directed per the package insert. 
Ibrutinib will be labeled by the clinical site as per local regulations.
For Phase 2 ibrutinib will be supplied or obtained according to local clinical study agreement and 
labeled in accordance with local regulations. 
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Please refer to local ibrutinib prescribing information for more details on known precautions, 
warnings, and adverse reactions (see current version of Prescribing Information).
7.2.7.2.
Ibrutinib Administration
Subjects should be instructed to take ibrutinib orally with a glass of water at approximately the 
same time each day.
7.2.7.3.
Ibrutinib Dose Modification
Ibrutinib dose may be modified in a stepwise manner for treatment-related toxicity according to 
the guidance provided in Table 29 or as determined by the Investigator in consultation with the
Medical Monitor. Reintroduction of ibrutinib following interruption may be done in a stepwise 
manner back to the full intended dose. Dose modifications must be recorded in the Dose 
Administration CRF.
Table 29:
Ibrutinib Dose Modification Levels
Starting 
Ibrutinib 
Dose
1st Dose 
Reduction
2nd Dose 
Reduction
3rd Dose 
Reduction
4th Reduction
420 mg 
QD
Pause until 
recovery, restart 
420 mg QD
Pause until 
recovery, reduce to 
280 mg QD
Pause until 
recovery, reduce to 
140 mg QD
Discontinue 
permanently
Abbreviations: QD = once a day.
Please refer to the ibrutinib PI for full details.
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7.2.10.
Definition of Dose-limiting Toxicity 
Dose-limiting toxicities will be evaluated during the DLT evaluation period for the subjects in 
Phase 1. The severity grading of adverse events will be determined according to NCI CTCAE 
Version 4.03 or higher. CRS is graded as per Appendix M.
A DLT will be defined as below: 

Death not related to disease progression

Grade 4 neurotoxicity

Grade 3 neurotoxicity of greater than 7 days’ duration 

Grade 3 neurotoxicity that does not revert to baseline within 28 days of the start date 
of the Grade 3 event
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
Grade 3 seizures that do not resolve to Grade ≤ 2 within 3 days 

Grade 4 CRS 

Grade 3 CRS that does not resolve to Grade ≤ 2 within 7 days 

Febrile neutropenia (defined by temperature ≥ 38.3°C and ANC < 0.5 x 109 /L) that 
does not resolve within 72 hours

Any increase in aspartate aminotransferase (AST) or ALT > 5 x ULN and concurrent 
increase in total bilirubin > 3 x ULN that is unrelated to CRS and has no other 
probable reason to explain the combination of increases 

Any cardiac, dermatologic, gastrointestinal, hepatic, pulmonary, renal/genitourinary, 
or neurologic Grade 3 or 4 event not pre-existing or not due to the underlying 
malignancy

Any other Grade 3 or 4 event deemed unexpected by the Investigator and considered 
a DLT upon evaluation by the SRC

Any AE requiring dose modification of the combination agent required based on a 
related AE or any treatment interruption greater than 2 weeks
For Arm A, the following additional combination treatment-related events will be considered 
DLTs (if occurring after start of durvalumab):

Grade ≥ 3 non-infectious colitis or non-infectious pneumonitis

Grade ≥ 3 immune-related adverse event (irAE) or other Grade ≥ 3 autoimmune 
toxicity (excluding B-cell aplasia) 
For Arm B, the following additional combination treatment-related events will be considered 
DLTs (if occurring after start of CC-122):

Grade 4 neutropenia lasting ≥ 7 days

Grade 3 or 4 thrombocytopenia with clinically significant bleeding

Grade 4 thrombocytopenia lasting > 24 hours
For Arm C, the following additional combination treatment-related events will be considered 
DLTs (if occurring after start of CC-220):

Grade 4 neutropenia lasting ≥ 7 days

Grade 3 or 4 thrombocytopenia with clinically significant bleeding
For Arm D, the following additional combination treatment-related events will be considered 
DLTs (if occurring after start of combination therapy):

Grade 4 neutropenia lasting ≥ 7 days

Grade 3 or 4 thrombocytopenia with clinically significant bleeding
For Arm E, the following additional combination treatment-related events will be considered 
DLTs (if occurring after start of combination therapy):

Grade ≥ 3 non-infectious colitis or non-infectious pneumonitis 
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
Grade ≥ 3 immune-related adverse event (irAE) or other Grade ≥ 3 autoimmune 
toxicity (excluding B-cell aplasia) 

Grade 2 immune-related eye pain or reduction in visual acuity that requires systemic 
treatment

Grade 2 eye pain or reduction in visual acuity that does not respond to topical therapy 
and that does not improve to Grade 1 within 2 weeks of initiation of topical therapy

Grade 4 anemia

Grade 3 hemolysis

Grade 3 or 4 thrombocytopenia with clinically significant bleeding
For Arm F, the following additional combination treatment-related events will be considered 
DLTs (if occurring after start of combination therapy):

Grade 4 anemia

Grade 4 neutropenia lasting ≥ 7 days

Grade 3 or 4 thrombocytopenia with clinically significant bleeding
Should a subject experience a suspected DLT, the treating investigator should contact the 
sponsor’s medical monitor prior to declaring the event a DLT. All DLT cases will also be 
discussed with the SRC during regular calls with sites and their respective investigators aiming 
to review and share all safety related events including but not limited to DLTs. 
Please see Section 10 for further details on AE reporting. 
7.2.11.
Overdose
Overdose, as defined for this protocol, refers to flu/cy (IV), durvalumab (IV), CC-122 (PO), CC-
220 (PO), ibrutinib (PO), nivolumab (IV), relatlimab (IV), CC-99282 (PO) or JCAR017 (IV). On 
a per-dose basis, an overdose is defined as the following amount over the protocol-specified dose 
of these drug(s) assigned to a given subject, regardless of any associated AEs or sequelae:

PO: any amount over the protocol-specified dose

IV:10% over the protocol-specified dose
On a schedule or frequency basis, an overdose is defined as anything more frequent than the 
protocol required schedule or frequency. On an infusion rate basis, an overdose is defined as any 
rate faster than the protocol-specified rate.
In the event of overdose the subject should be observed closely for signs of toxicity. Appropriate 
supportive treatment should be provided if clinically indicated.
Complete data about drug administration, including any overdose, regardless of whether the 
overdose was accidental or intentional, should be reported in the CRF. See Section 10 for the 
reporting of AEs associated with overdose.
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8.
CONCOMITANT MEDICATIONS AND PROCEDURES
8.1.
Permitted Concomitant Medications and Procedures
Medications will be recorded as shown in Table 30. Subjects should be discouraged from use of 
illicit drugs, herbal remedies, self-prescribed drugs, tobacco products, or excessive alcohol at any 
time during the clinical study.
Table 30:
Reporting Periods for Concomitant Medications
Arm
Start
End
Required Reporting
All
Informed Consent
Initiation of LD chemotherapy or first 
dose of combination agent, whichever 
occurs first
Medications taken by the subject 
at the time of an AE related to 
protocol-mandated procedures or 
for active medical history 
conditionsa
A
Start of LD chemotherapy
90 days after last dose of LD 
chemotherapy, JCAR017 infusion, or 
durvalumab (whichever is later)
All medications
B
Start of LD chemotherapy
90 days after last dose of LD 
chemotherapy or JCAR017, or 28 
days after last dose of CC-122 
(whichever is later)
C
Start of LD chemotherapy
90 days after last dose of LD 
chemotherapy or JCAR017, or 28 
days after last dose of CC-220 
(whichever is later)
D
Start of ibrutinib
90 days after last dose of LD 
chemotherapy or JCAR017, or 28 
days after last dose of ibrutinib 
(whichever is later)
E
Start of LD chemotherapy
90 days after last dose of LD 
chemotherapy, JCAR017, nivolumab 
or relatlimab (whichever is later)
F
Start of LD chemotherapy
90 days after last dose of LD 
chemotherapy or JCAR017, or 28 
days after last dose of CC-99282
(whichever is later)
All
End of previous period
End of study
Only medications ongoing at the 
time of AEs related to any study 
procedure or JCAR017 or 
combination agent will be 
collected
Abbreviations: AE = adverse event; CCGs = CRF compliance guidelines; CRF = Case report form; LD = lymphodepleting.
a Medications given, procedures and transfusions performed for a clinically significant condition unrelated to protocol-mandated 
procedures should be reported as described in the CCGs.
Over the course of this study, additional medications may be required to manage aspects of the 
disease state of the subjects (refer to Section 8.1.1), including side effects from trial treatments or 
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disease progression. Supportive care, including, but not limited to antiemetic medications, may 
be administered at the discretion of the Investigator. 
All concomitant treatments, including blood and blood products (see Section 8.1.2), used from 
30 days prior to first dose of any IP must be reported on the CRF. 
For information regarding other drugs that may interact with any IP and affect its metabolism, 
pharmacokinetics, or excretion, please see the IB and/or local package insert.
Vaccination with a killed vaccine is permitted at any time with consultation with the medical 
monitor.
Due to the large amount of data generated during hospitalizations, a targeted concomitant 
medication collection approach will be utilized for the CRF. Therefore, the following 
medications should NOT be entered on the CRF during inpatient and Intensive Care Unit (ICU)
stays:

IV fluids

Heparin flushes

Stool softeners

Vitamins, minerals, health supplements

Saline

Lotions
8.1.1.
Anticancer Treatments between Leukapheresis and Lymphodepleting 
Chemotherapy
If necessary, anticancer treatment is allowed for disease control while JCAR017 is being 
manufactured (ie, after leukapheresis and prior to lymphodepleting chemotherapy). 
Chemotherapy is allowed if completed at least 7 days prior to the start of lymphodepleting 
chemotherapy. If other agents are used, the washout periods noted in the exclusion criteria (see 
Section 4.3) must be met. The use of therapeutic agents with little/no evidence in the scientific 
literature for NHL should be discussed with Celgene. Local radiation is allowed to a single lesion 
or subset of lesions if other un-irradiated PET-positive lymphoma lesions are present. If 
anticancer treatment is necessary during this time, the pre-JCAR017 evaluation PET and 
CT/MRI assessments and other pre JCAR017 study procedures (see Section 6.1.3) must be 
performed after the anticancer treatment has been completed. The subject must continue to have 
PET-positive disease (except Arm D) and meet pre-JCAR017 eligibility criteria pertaining to 
adequate organ function, active infections, pregnancy, and washout of prior therapy before 
initiation of LD chemotherapy.
8.1.2.
Growth Factors and Transfusions of Blood and Blood Products 
Secondary neutropenia prophylaxis with granulocyte colony-stimulating factor (G-CSF) is 
recommended for subjects in Arms B, C and F. Secondary prophylaxis with G-CSF for subjects 
who experienced Grade 4 neutropenia or neutropenic fever from a prior cycle of CC-122 or 
CC-220 (for which primary prophylaxis was not received), or for subjects enrolled in Arm F who 
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experience Grade 4 neutropenia or neutropenic fever lasting 7 days should be initiated after 
discussion with the sponsor. 
If G-CSF is given following lymphodepleting chemotherapy to support hematopoiesis it should 
be stopped at least 2 days before the start of combination therapy where this is dependent on 
ANC or platelet count.  
Other growth factors (eg, erythropoietin) may be prescribed after leukapheresis or at any time 
during the treatment and follow-up periods at the Investigator’s discretion once a subject has 
experienced cytopenic or myelosuppressive events. For all arms, growth factors or transfusions 
of blood or blood products cannot be administered during the Screening period to increase a 
subject’s blood values in order to meet entry criteria (see Section 4).
8.1.3.
Thromboembolic Event Prophylaxis
Subjects and investigators are advised to be observant for the signs and symptoms of 
thromboembolism. Subjects should be instructed to seek medical care if they develop symptoms 
such as shortness of breath, chest pain, or arm or leg swelling. It is recommended that the 
Investigator carefully assess an individual subject’s underlying risk for thromboembolism and 
bleeding and consider prophylactic measures with anti-coagulation or anti-platelet agents as per 
institutional or clinical standards. Thromboembolic event prophylaxis is mandatory for subjects 
enrolled in Arm C.
8.2.
Prohibited Concomitant Medications and Procedures
The following medications are considered exclusionary or should be used with caution during 
the study. The sponsor must be notified if a subject receives any of these during the study.

Any investigational anticancer therapy

Any concurrent chemotherapy, radiation therapy, immunotherapy, biologic or 
hormonal therapy for cancer treatment

Concurrent use of hormones for non-cancer-related conditions (eg, insulin for 
diabetes and hormone replacement therapy) is acceptable

Immunosuppressive medications including, but not limited to systemic corticosteroids 
at doses exceeding 20 mg/day of prednisone or equivalent, methotrexate, 
azathioprine, and tumor necrosis factor alpha (TNF-α) blockers
Note: Use of immunosuppressive medications for the management of IP-related AEs 
or in subjects with contrast allergies is acceptable. In addition, use of inhaled and 
intranasal corticosteroids is permitted.

Herbal and natural remedies are to be avoided

Concurrent use of St John´s wort

Live attenuated vaccines during the study through 30 days after the last dose of 
investigational product (100 days for subjects who have received nivolumab or 
relatlimab on Arm E)
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The following medications are prohibited until lack of response, subsequent therapy for 
lymphoma, or 1 year following JCAR017 treatment, whichever comes first: 

Steroids: therapeutic doses (> 20 mg/day of prednisone or equivalent) unless used for 
treatment of CRS, NT or MAS/HLH. Therapeutic doses may be used in life-
threatening situations and for other medical conditions when indicated, or after loss of 
detectable JCAR017 cells. Pre-treatment containing steroids may be given for 
necessary medications (eg, IVIG) after discussion with the Sponsor. Pre-medication 
with steroids for JCAR017 administration is not allowed. Physiologic replacement 
dosing of steroids is allowed. Topical steroids, inhaled steroids, and intrathecal 
steroids for CNS relapse prophylaxis are permitted.
The following medications are prohibited during the treatment and follow-up periods unless used 
as an anticancer agent after lack of adequate response to JCAR017 or progression of lymphoma: 

Donor lymphocyte infusion (DLI)

GVHD therapies (eg, calcineurin inhibitors, methotrexate or other chemotherapeutics, 
mycophenolate, rapamycin, thalidomide, immunosuppressive antibodies such as anti-
TNF, anti-IL6, or anti-IL6R) 

Anticancer agents, excluding lymphodepleting chemotherapy and agents used for 
treatment of uncontrolled JCAR017 proliferation or sCRS 

Cetuximab, or other anti- epidermal growth factor receptor (EGFR) treatments, unless 
intended for treatment of uncontrolled JCAR017 proliferation or sCRS 

Experimental agents 

Radiation, unless needed for local control of a single tumor lesion in the presence of 
other non-irradiated PET-positive lesions 
8.2.1.
Additional Concomitant Medication Guidance for Arm B 
Based on in vitro studies, CYP3A4/5 and CYP1A2 appear to be the major isozymes involved in 
oxidative metabolism of CC-122, with very minor contributions by other CYP enzymes, 
including CYP2C8 and CYP2C19. Hence, caution should be used when co-administering CC-
122 with drugs that are known strong inducers or inhibitors of CYP3A4/5 or CYP1A2, as these 
may affect the exposure to CC-122. The effects of these compounds on the exposure to CC-122 
have not been evaluated in a clinical setting. Examples of these drugs include the following:

CYP3A4/5 inhibitors: telithromycin, clarithromycin, atazanavir, indinavir,
itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, and saquinavir.

CYP3A4/5 inducers: rifampin, phenytoin and carbamazepine.

CYP1A2 inhibitors: ciprofloxacin, enoxacin and fluvoxamine.
A comprehensive listing of drugs that are CYP3A4 inhibitors can be accessed online at the 
following address: http://medicine.iupui.edu/clinpharm/ddis/table.aspx.
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8.2.2.
Additional Concomitant Medication Guidance for Arm C 
Medications that are strong inhibitors or inducers of CYP3A4/5 are prohibited. Of note, any 
antibiotics/antifungals listed as strong inhibitors or inducers of CYP3A4/5 should be avoided and 
replaced by alternate treatment. In general, azole antifungals such as itraconazole and the 
antibiotics clarithromycin and rifampin should be avoided. Also, grapefruit, St. John’s Wort, and 
related products are prohibited while participating in this study. Please refer to Appendix V for a 
list of medications that are strong inhibitors or inducers of CYP3A4/5. Please note this list is not 
exhaustive. If there are any questions regarding whether a medication is a strong CYP3A4/5 
inhibitor or inducer, please contact the Medical Monitor or designee.
8.2.3.
Additional Concomitant Medication Guidance for Arm D 
The coadministration of ibrutinib with a strong or moderate CYP3A inhibitor may increase 
ibrutinib plasma concentrations. Increased ibrutinib concentrations may increase the risk of drug-
related toxicity. Dose modifications of ibrutinib are recommended when used concomitantly with 
posaconazole, voriconazole and moderate CYP3A inhibitors.
Concomitant use of other strong CYP3A inhibitors should be avoided. Hold ibrutinib if these 
inhibitors will be used short-term (such as anti-infectives for seven days or less).
Grapefruit and Seville oranges during ibrutinib treatment should be avoided, as these contain 
strong or moderate inhibitors of CYP3A.
The coadministration of ibrutinib with strong CYP3A inducers may decrease ibrutinib 
concentrations and therefore should be avoided. Please refer to Appendix V for a list of 
medications that are strong inhibitors or inducers of CYP3A4/5. Please note this list is not 
exhaustive. If there are any questions regarding whether a medication is a strong CYP3A4/5 
inhibitor or inducer, please contact the Medical Monitor or designee.
Please refer to ibrutinib prescribing information for full details.
8.2.4.
Additional Concomitant Medication Guidance for Arm F
It is recommended to initiate growth factor support for neutropenia of Grade 3 or higher while 
subjects are receiving combination therapy with CC-99282. 
CC-99282 is a substrate of CYP3A4/5. Drugs that are strong inhibitors or inducers of CYP3A4/5 
should be avoided. Examples of these drugs include, but are not limited to:

CYP3A4/5 inhibitors: atazanavir, clarithromycin, indinavir, itraconazole, 
ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, and telithromycin.

CYP3A4/5 inducers: carbamazepine, phenytoin, and rifampin.
If use of one of these drugs becomes necessary, the risks and benefits should be discussed with 
the Sponsor’s study physician prior to its concomitant use with CC-99282.
Please refer to the CC-99282 IB for full details.
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8.3.
Required Concomitant Medications and Procedures
Lymphodepleting regimens accompany JCAR017 administration and utilize cyclophosphamide 
and fludarabine. Please refer to the currently approved cyclophosphamide and fludarabine 
phosphate package insert.
Premedication should be given prior to JCAR017 and durvalumab administration. Please refer 
respectively to Section 7.2.2.3 and Section 7.2.4.2 for the details.
Supportive care for the management of CRS is detailed in Appendix M. In some cases, 
tocilizumab, an anti-IL-6R-antibody, may be required to treat toxicities such as severe cytokine 
release syndrome. All JCAR017 global sites (eg, US, EU) must have at least 2 doses of 
tocilizumab available prior to infusion per a given subject. It is recommended to resupply in case 
tocilizumab is given Please refer to the currently approved Actemra®/ RoActemra® package 
insert. The preferred dose to intervene in subjects with CRS is 8 mg/kg.
In some cases, dexamethasone may also be given in combination with tocilizumab. The preferred 
dose for dexamethasone in subjects with CRS is between 10 to 20 mg (see Appendix M). 
An additional anti-IL-6 antagonist, siltuximab, should also be considered in the event of sCRS. 
Please refer to the current approved package insert.
Thromboembolic event prophylaxis will be started on the day CC-220 is started for subjects in 
Arm C and continued until the end of CC-220 treatment.
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9.
STATISTICAL CONSIDERATIONS
9.1.
Overview
This study is a Phase 1/2, multi-center, open-label study of the combination of JCAR017 and 
immunomodulatory agents in subjects with R/R aggressive B-cell NHL. Phase 1 is a dose and 
schedule finding phase and Phase 2 is an expansion phase in which additional subjects will be 
enrolled at the recommended Phase 2 dose and schedule established in Phase 1. Rules for 
enrollment prioritization between arms will be specified each time additional arms will be added.
The primary objective of Phase 1 is to assess the safety and to determine the RP2D of the 
JCAR017 combinations per arm using a BOIN design. The combination agents are as follows:

Arm A: durvalumab

Arm B: CC-122

Arm C: CC-220 (iberdomide)

Arm D: ibrutinib

Arm E: nivolumab ± relatlimab

Arm F: CC-99282
Within an arm, a dose expansion cohort (Phase 2) may be opened at any dose and schedule that 
has been shown to be safe with at least 6 DLT evaluable subjects through the DLT period. The 
primary objective of Phase 2 is to evaluate hierarchically the preliminary efficacy of JCAR017 
first on CR rate (CRR) at 3 months and subsequently on CRR at 6 months when administered in 
combination with checkpoint inhibitors or immunomodulatory compounds. 
The secondary objectives (Phase 1 and Phase 2 in each arm) are to further evaluate safety, other 
efficacy endpoints and to characterize the PKs of JCAR017 and the respective combination 
agent.
9.2.
Study Population Definitions
For each arm in this study, the following analysis populations will be defined for the analysis and 
presentation of the data.
9.2.1.
Screened Set
The Screened set will include all subjects who have signed informed consent.
9.2.2.
Enrolled Set
The Enrolled set will include all subjects who have signed informed consent, who meet all 
eligibility criteria at screening and undergo leukapheresis (Arms A, B, C, E and F) or those who 
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have signed informed consent, meet all eligibility criteria at screening and either receive
combination therapy or undergo leukapheresis (Arm D).
9.2.3.
Leukapheresed Set
The Leukapheresed set will include all subjects who have undergone leukapheresis.
9.2.4.
JCAR017 Treated Set
The JCAR017 Treated set will include all subjects who have received an infusion of conforming 
JCAR017 cell product. 
9.2.5.
Combination Treated Set
The Combination Treated set will include all subjects who have received an infusion of 
conforming JCAR017 cell product and at least one dose of the combination agent.
9.2.6.
Safety Set
The Safety set will include all subjects who have received an infusion of conforming JCAR017 
cell product or at least one dose of the combination agent.
9.2.7.
DLT Evaluable Set
The DLT evaluable set includes all subjects who have either received an infusion of conforming 
JCAR017 cell product and at least one dose of the combination agent and have completed the 
DLT evaluation period (see Section 9.3.1), or who have received an infusion of conforming 
JCAR017 cell product and at least one dose of the combination agent and have experienced at 
least one DLT prior to completion of the DLT evaluation period.
9.2.8.
Efficacy Evaluable Set
The Efficacy Evaluable set includes subjects in the Combination Treated set who have a baseline 
and at least one valid post-baseline tumor response assessment.
9.3.
DLT Related Definitions
9.3.1.
Definition of DLT Evaluation Period
Subjects enrolled in Phase 1 will be observed for DLTs as follows:
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9.3.1.1.
Arms A, B and C
Subjects will be observed for DLT from JCAR017 infusion until 28 days after the first dose of 
the combination agent.
9.3.1.2.
Arm D
Subjects will be observed for DLT from the start of JCAR017 infusion until 28 days after 
JCAR017 infusion.
9.3.1.3.
Arm E
Subjects will be observed for DLT from the start of JCAR017 infusion until 28 days after the 
first dose of the combination agent.
9.3.1.4.
Arm F
Subjects will be observed for DLT from the start of JCAR017 infusion until 28 days after the 
first dose of the combination agent.
9.3.2.
Definition of a Subject Evaluable for DLTs
Subjects enrolled in Phase 1 are considered evaluable for DLTs if they received an infusion of 
conforming JCAR017 cell product and at least one dose of the combination agent and complete 
the specified DLT evaluation period or if they have received an infusion of conforming 
JCAR017 cell product and at least one dose of the combination agent and experience a DLT 
during the DLT evaluation period. Subjects who are unable to start combination therapy within a 
given, subcohort-specific timeframe are not evaluable for DLT. 
Non DLT evaluable subjects will be replaced with another subject at the same dose level. 
Additional subjects within any dose cohort may be enrolled at the discretion of the SRC.
9.4.
Sample Size and Power Considerations
9.4.1.
Phase 1
In each arm, dose escalation or de-escalation within any cohort will be based on the BOIN 
algorithm. With the target DLT rate of 0.30, the BOIN escalation boundary is λe=0.236 and the 
de-escalation boundary is λd=0.358. The BOIN dosing decision table is provided in Table 9. 
The BOIN design is a Bayesian dose-finding method that optimizes subject ethics by minimizing 
the chance of exposing subjects to sub-therapeutic and overly toxic doses. The BOIN design 
yields an average performance comparable to that of the continual reassessment method (CRM) 
in terms of selecting the MTD, but has a lower risk of assigning subjects to sub-therapeutic or 
overly toxic doses (ie, better subject ethics). 
In each arm, enrollment into Phase 1 will be staggered such that the first 6 subjects in each 
subcohort will enter the DLT period at intervals of at least 1 week. A longer interval may be 
specified for a specific arm (see Section 3.1.9). Until a subcohort has 6 subjects with complete 
DLT information and has been shown to be safe, no more than 6 subjects can be in the DLT 
period simultaneously across subcohorts of a given arm. Enrollment to the next dose level will be 
prioritized if open for enrollment. 
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for study treatment but not able to successfully generate a JCAR017 cell product, along with the 
reason(s) for manufacturing failure, will be summarized per cohort and per arm. Summary of 
subjects enrolled by site will be provided. Summary of subjects with protocol deviations and 
violations will be provided per cohort and per arm.
9.6.2.
Phase 2
Summaries of subject disposition will be provided by arm for the Screened set, Enrolled set and 
JCAR017 Treated set. The number and percentage of subjects who are eligible for study 
treatment but not able to successfully generate a JCAR017 cell product, along with the reason(s) 
for manufacturing failure, will be summarized per arm. Summary of subjects enrolled by site will 
be provided. Summary of subjects with protocol deviations and violations will be provided per 
arm.
9.7.
Efficacy Analysis
For each arm, the primary efficacy analysis will be based on the Combination Treated set. 
JCAR017 Treated set, Efficacy Evaluable set and the Leukapheresed set will be used as 
supportive analysis when applicable.
For binary endpoints such as overall response rate (ORR), the frequency distribution (n, %) will 
be provided. The point estimate together with two-sided exact 95% confidence intervals (CI) will 
be provided. 
For time-to-event endpoints such as duration of response (DOR), event-free survival (EFS), 
progression-free survival (PFS) and overall survival (OS), the Kaplan-Meier product limit 
method will be used to estimate the survivorship function. Event rates at specific time points will 
be estimated from the Kaplan-Meier curves. Medians together with two-sided 95% confidence 
intervals will be calculated.
9.7.1.
Primary Efficacy Analysis (Phase 2)
The primary efficacy endpoints of Phase 2 are CRR at 3 months post-JCAR017 infusion and 
subsequently CRR at 6 months post-JCAR017 infusion. The CRR is defined as the proportion of 
subjects achieving a CR according to the Lugano Classification, prior to start of another non-
study anticancer therapy.
For each arm, primary analysis of the proportion of subjects achieving a CR at 3 months and 6 
months post-JCAR017 infusion will be done using an exact binomial test (0.05 two-sided 
significance level) and in a Bayesian framework. Subjects from Phase 1 under RP2D will be 
used during the analysis of the Phase 2 data as prior information during both interim monitoring 
and final analysis (prior for Phase 2 based on a combination of Jeffreys prior and CR numbers 
during Phase 1 in a beta binomial model).
Bayesian posterior and predictive probability of success will be used for the monitoring of 
efficacy on CRR at 3 months after JCAR017 infusion during the dose expansion phase. Phase 2 
will be stopped for futility at interim monitoring if posterior predictive probability of success is 
smaller than 10% after 15 evaluable subjects. 
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9.8.
Safety Analysis
Safety analysis including treatment-emergent adverse events (TEAEs) and laboratory findings 
will be based on both the JCAR017 Treated set and Combination Treated set. Data will be
aggregated for all cohorts per arm as well as separately for each cohort per arm. Literature 
“book” values will be utilized for this study.
TEAEs ≥ Grade 3 in subjects infused with JCAR017 in a clinical trial setting include neurologic 
toxicities, such as encephalopathy, hypotension, cytokine release syndrome, febrile neutropenia,
and hypoxia. 
TEAEs ≥ Grade 3 in subjects treated with durvalumab in a clinical trial setting include irAEs, 
such as pneumonitis, hypersensitivity reactions, cytopenias, infections, venous thromboembolism 
and endocrine disorders. 
The following safety assessments will also be performed:

The timing and length of inpatient hospitalization

Physical exam 

MMSE

Laboratory evaluations to monitor closely for neurologic changes, CRS, and fever 

Expected cytopenias and potential infections attributable to the lymphodepleting 
chemotherapy
9.8.1.
Phase 1 DLT
Dose-limiting toxicity will be listed by cohort and arm using the DLT Evaluable analysis set.
Safety analysis including TEAEs and laboratory findings will be based mainly on the JCAR017
Treated set and Combination Treated set per cohort and per arm.
9.8.2.
Adverse Events
Adverse events will be coded using MedDRA system organ class (SOC) and preferred term 
(PT).
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The severity of each adverse event will be graded by the Investigator using Common 
Terminology Criteria for Adverse Events (CTCAE) version 4.03 or higher, unless otherwise 
specified in the protocol. If CTCAE criteria do not exist for a given event, the Investigator 
should use one of the following: Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), Grade 4 
(life-threatening), or Grade 5 (fatal) to describe the maximum intensity of the adverse event.
Related AEs are those for which the Investigator selects “Related” to JCAR017 or any other 
combination drugs on the AE CRF. Relatedness will always default to the Investigator’s choice, 
not that of the medical monitor. AEs suspected to be related to any study drug, will be tabulated 
as JCAR017 alone, JCAR017 in combination or combination drug alone.
Adverse events will be identified and captured as SAEs if they meet the definition for SAE.
A JCAR017 TEAE is defined as any AE that occurs or worsens after the JCAR017 infusion and 
up to 90 days after the JCAR017 infusion.
A combination TEAE is defined as any AE that occurs or worsens after the first JCAR017 
infusion and up to 90 days after the dose of JCAR017 or 90 days after the last dose of 
durvalumab, 28 days after the last dose of CC-122, ibrutinib or CC-99282, or 90 days after the 
last dose of nivolumab or relatlimab, whichever occurs last.
All AEs will be listed. The focus of AE summarization will be on JCAR017 TEAEs with 
additional combination period (pre-JCAR017 and post-JCAR017).
Adverse event summaries will provide the number and percentage of subjects with TEAEs by 
SOC and PT, based on the JCAR017 Treated set and Combination Treated set as follows (a 
brief-high level summary will also be provided):

All TEAEs;

All TEAEs by severity grade;

Grade ≥ 3 TEAEs;

All treatment related AEs;

Treatment related Grade ≥ 3 AEs;

All SAEs;

All treatment-related SAEs;

All AEs leading to treatment discontinuation;

All AEs leading to death;

AEs leading to study discontinuation
Multiple occurrence of the same events will be counted only once per subject in each summary.
Adverse events will be summarized and listed first by SOC in descending order of incidence and 
then by PT (within each SOC), also in descending order of incidence. In summaries by severity 
grade, the most severe grade will be used for those AEs that occur more than once in an 
individual subject during the study.
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In addition to the above summary tables, all TEAEs and SAEs will be summarized by SOC only 
and by PT only in order of descending incidence.
9.9.
Laboratory Evaluations
The focus of the laboratory data summarization will be on the JCAR017 treatment-emergent and 
combination treatment-emergent laboratory abnormalities using the JCAR017 Treated set and 
Combination Treated set. 
JCAR017 treatment-emergent laboratory abnormalities are defined as an abnormality that, 
compared to baseline, worsens by at least one grade after the JCAR017 infusion and up to 3 
months after the JCAR017 infusion.
Combination treatment-emergent laboratory abnormalities are defined as an abnormality that, 
compared to baseline, worsens by at least one grade after the JCAR017 infusion or after the start 
of the combination, whichever occurs first and up to 3 months after the dose of JCAR017, 3 
months after the last dose of the combination agent, whichever occurs last.
All laboratory data will be listed with a variable indicating whether the event is treatment-
emergent.
9.9.1.
Numeric Laboratory Results
Summaries of laboratory data will be based on observed data and will be reported using 
conventional units. Baseline, raw values, and changes from baseline will be summarized using 
descriptive statistics for each laboratory test specified in the study protocol. 
9.9.2.
Graded Laboratory Values
Applicable hematological and serum biochemistry laboratory data will be programmatically 
graded according to CTCAE (Version 4.03 or higher) severity grade: mild (Grade 1), moderate 
(Grade 2), severe (Grade 3), or life threatening (Grade 4). Grade 0 includes all non-missing 
values that do not meet criteria for an abnormality of at least Grade 1. Some laboratory tests have 
criteria for both increased and decreased levels; analyses for each direction (ie, increased, 
decreased) will be presented separately.
9.9.3.
Summaries of Laboratory Abnormalities
All laboratory data will be listed. The focus of laboratory data summarization will be on 
JCAR017 treatment-emergent laboratory abnormalities. Summaries (number and percentage of 
subjects) of baseline, post-baseline at each visit, and worst post-baseline treatment-emergent 
laboratory abnormalities will be provided. Subjects will be categorized according to the most 
severe abnormality grade. All summaries of laboratory abnormalities will be based on the 
JCAR017 Treated set and Combination Treated set.
Shift tables will be presented by showing the change in CTCAE severity grade from baseline to 
each post-baseline visit and to the maximum post-baseline grade. For parameters for which a 
CTCAE severity scale does not exist, shift tables will be presented showing change in results 
from the baseline value (low, normal, and high) to each post-baseline visit and to the worst post-
baseline value (low, normal, and high).
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9.10.
Interim Analysis
The interim safety and efficacy findings at the end of Phase 1 subcohorts, and the primary and 
updated analysis in Phase 2 may be submitted for public presentation. In general, each subcohort 
with different combination therapies in different subject populations will be analysed separately, 
but subcohorts may be pooled based on the need of analyses. In addition, interim data may also 
be pooled for aggregate safety and efficacy based on analyses performed for regulatory 
authorities (e.g. DSUR) or for presentation to the DSMB.
9.11.
Other Topics
9.11.1.
Safety Review Committee 
During Phase 1, the SRC will be convened to recommend a Phase 2 dose and schedule for each 
combination treatment arm based on an integrated assessment of the safety, PK and Pd data, and 
preliminary efficacy information. The SRC may also override the BOIN algorithm for safety 
concerns.
During Phase 2, the SRC will be convened to evaluate the safety profile and tolerability.
This committee will be composed of the medical monitor, drug safety physician, and statistician 
as well as selected active Investigators to be identified at the start of the study. Operational 
details for the SRC will be detailed in a separate SRC charter.
9.11.2.
Data Safety Monitoring Board 
An independent DSMB will review cumulative study data over the course of the study to 
evaluate safety, protocol conduct, and scientific validity and integrity of the trial. The DSMB, 
composed of a statistician and selected physicians with experience in hematology/oncology 
and/or T cell therapy, will be assembled under a dedicated charter specifically developed for 
safety oversight of the study. DSMB members will not be actively involved in the study design, 
conduct, or subject accrual and must not have financial, proprietary, professional, or other 
interests that may affect impartial, independent decision making.
The DSMB will be convened prior to enrollment of the first subject on the protocol and will 
meet approximately quarterly throughout the trial and as needed to address any safety issues that 
may arise. Subject safety will be evaluated as specified in DSMB charter. The DSMB will 
provide advice to the Sponsor as outlined in the DSMB charter. The effectiveness of the risk 
mitigation plan will be reviewed by the DSMB at each meeting. Operational details for the 
DSMB will be detailed in the DSMB charter.
9.11.3.
Pharmacokinetics
Maximum concentration, time to maximum concentration, area under the curve of JCAR017 will 
be calculated using noncompartmental methods. JCAR017 concentrations and PK parameters 
will be summarized descriptively. Persistence of JCAR017 will be summarized. In addition, 
concentrations of the respective combination agents will be summarized descriptively. Full 
details will be included in the SAP.
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10.
ADVERSE EVENTS
10.1.
Monitoring, Recording and Reporting of Adverse Events
An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen 
in a subject during the course of a study. It may be a new intercurrent illness, a worsening 
concomitant illness, an injury, or any concomitant impairment of the subject’s health, including 
laboratory test values (as specified by the criteria in Section 10.3), regardless of etiology. Any 
worsening (ie, any clinically significant adverse change in the frequency or intensity of a pre-
existing condition) should be considered an AE.
Abuse, withdrawal, sensitivity or toxicity to an investigational product should be reported as an 
AE. Overdose, accidental or intentional, whether or not it is associated with an AE should be 
reported on the overdose CRF (see Section 7.2.11 for the definition of overdose). Any sequela of 
an accidental or intentional overdose of an investigational product should be reported as an AE 
on the AE CRF. If the sequela of an overdose is an SAE, then the sequela must be reported on an 
SAE report form and on the AE CRF. The overdose resulting in the SAE should be identified as 
the cause of the event on the SAE report form and CRF but should not be reported as an SAE 
itself.
In the event of overdose, the subject should be monitored as appropriate and should receive 
supportive measures as necessary. There is no known specific antidote for JCAR017, 
durvalumab, CC-122, CC-220, ibrutinib, nivolumab, relatlimab, CC-99282, or flu/cy overdose. 
Actual treatment should depend on the severity of the clinical situation and the judgment and 
experience of the treating physician.
All subjects will be monitored for AEs during the study. Assessments may include monitoring of 
any or all of the following parameters: the subject’s clinical symptoms, laboratory, pathological, 
radiological or surgical findings, physical examination findings, or findings from other tests 
and/or procedures.
Adverse events must be recorded as shown in Table 31. If they meet the seriousness criteria, they 
will be reported to Drug Safety as provided in Section 10.5.
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Table 31:
Recording Periods for Adverse Events
Arm
Start
End
Required Recording
All
Signing of informed 
consent
Start of LD chemotherapy or 
investigational product, 
whichever is earlier (except 
Arm D which is until start of 
ibrutinib)
AEs related to any protocol-
mandated procedurea
Each AE with a change in toxicity 
grade will be recorded in the CRF 
as a separate AE record
A
Start of LD 
chemotherapy
90 days after JCAR017 infusion 
or last dose of durvalumab 
(whichever is later)
All AEs
Each AE with a change in toxicity 
grade will be recorded in the CRF 
as a separate AE record
B
Start of LD 
chemotherapy
90 days after JCAR017 infusion 
or 28 days after last dose of 
CC-122 (whichever is later)
C
Start of LD 
chemotherapy
90 days after JCAR017 infusion 
or 28 days after last dose of 
CC-220 (whichever is later)
D
Start of ibrutinib 
90 days after JCAR017 infusion 
or 28 days after last dose of 
ibrutinib (whichever is later)
E
Start of LD 
chemotherapy
90 days after JCAR017 infusion 
or last dose of relatlimab or 
nivolumab (whichever is later)
F
Start of LD 
chemotherapy
90 days after JCAR017 infusion 
or 28 days after last dose of 
CC-99282 (whichever is later)
All
End of previous period
End of study
Only AEs related to any study 
procedure or JCAR017 or 
combination agent will be 
collected; changes in toxicity grade 
will be recorded as a single event 
with the highest toxicity grade 
experienced at any time during the 
event recorded
Abbreviations: AE = adverse event; CCGs = CRF compliance guidelines; CRF = Case report form; LD = 
lymphodepleting.
a Any clinically significant conditions/events unrelated to study procedures should be reported either in medical 
history or as an adverse event as described in the CCGs.
If a subject receives lymphodepleting therapy but not JCAR017, all AE/SAEs should be 
recorded/reported for 30 days following the last dose of lymphodepleting chemotherapy.
Serious adverse events made known to the Investigator at any time thereafter that are suspected 
of being related to IP will be recorded as well. Documentation must be supported by an entry in 
the subject’s source document. A diagnosis or syndrome should be recorded on the AE page of 
the CRF rather than the individual signs or symptoms of the diagnosis or syndrome. In addition 
to recording CRS as a diagnosis, the signs and symptoms of CRS will be recorded on a separate 
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CRF. Any medical condition already present prior to first LD chemotherapy should not be 
reported as an AE unless the medical condition is related to any study procedure and increases in 
severity. In this case, it should be reported as an AE and indicated as a worsening event.
Inpatient or ICU stays, while anticipated, are not scheduled protocol-defined visits. In addition, 
inpatient or ICU admissions can generate large amounts of clinical data (eg, multiple 
concomitant medications, frequent concomitant medication dose changes, laboratory values, and 
vital sign assessments). Therefore, targeted collection of data from inpatient or ICU stays, as 
well as a separate CRF for detailing specific adverse events of special interest (AESI; ie, signs 
and symptoms of CRS and neurotoxicity), will be utilized for the purpose of adequately 
describing the expected risks of JCAR017 and the recommendations for managing these risks.
AEs and SAEs will be recorded on the AE page of the CRF and in the subject’s source 
documents. All SAEs meeting the criteria described in Table 31 must be reported to Celgene 
Drug Safety within 24 hours of the Investigator’s knowledge of the event by facsimile, or other 
appropriate method, using the SAE Report Form, or approved equivalent form.
10.2.
Evaluation of Adverse Events
A qualified Investigator will evaluate all adverse events as to: 
10.2.1.
Seriousness 
An SAE is any AE occurring at any dose that:

Results in death;

Is life-threatening (ie, in the opinion of the Investigator, the subject is at immediate 
risk of death from the AE);

Requires inpatient hospitalization or prolongation of existing hospitalization 
(hospitalization is defined as an inpatient admission, regardless of length of stay);

Results in persistent or significant disability/incapacity (a substantial disruption of the 
subject’s ability to conduct normal life functions);

Is a congenital anomaly/birth defect;

Constitutes an important medical event.
Important medical events are defined as those occurrences that may not be immediately life-
threatening or result in death, hospitalization, or disability, but may jeopardize the subject or 
require medical or surgical intervention to prevent one of the other outcomes listed above.
Medical and scientific judgment should be exercised in deciding whether such an AE should be 
considered serious.
Events not considered to be SAEs are hospitalizations for:

a standard procedure for protocol therapy administration. However, hospitalization or 
prolonged hospitalization for a complication of therapy administration will be 
reported as an SAE. 

routine treatment or monitoring of the studied indication not associated with any 
deterioration in condition.
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
the administration of blood or platelet transfusion as routine treatment of studied 
indication. However, hospitalization or prolonged hospitalization for a complication 
of such transfusion remains a reportable SAE.

a procedure for protocol/disease-related investigations (eg, surgery, scans, endoscopy, 
sampling for laboratory tests, bone marrow sampling). However, hospitalization or 
prolonged hospitalization for a complication of such procedures remains a reportable 
SAE.

hospitalization or prolongation of hospitalization for technical, practical, or social 
reasons, in absence of an AE.

a procedure that is planned (ie, planned prior to start of treatment on study); must be 
documented in the source document and the CRF. Hospitalization or prolonged 
hospitalization for a complication remains a reportable SAE.

an elective treatment of or an elective procedure for a pre-existing condition, 
unrelated to the studied indication, that has not worsened from baseline. 

emergency outpatient treatment or observation that does not result in admission, 
unless fulfilling other seriousness criteria above.
If an AE is considered serious, both the AE page/screen of the CRF and the SAE Report Form 
must be completed.
For each SAE, the Investigator will provide information on severity, start and stop dates, 
relationship to the IP, action taken regarding the IP, and outcome.
10.2.2.
Severity/Intensity
For both AEs and SAEs, the Investigator must assess the severity/ intensity of the event. 
The severity/intensity of AEs will be graded based upon the subject’s symptoms according to the 
current active minor version of the Common Terminology Criteria for Adverse Events (CTCAE, 
Version 4.03 or higher); CRS is to be graded as per Appendix M.
AEs that are not defined in the CTCAE should be evaluated for severity/intensity according to 
the following scale or Version 3.0 of NCI CTCAE as in the case of TFR (refer to Table 41):

Grade 1 = Mild – transient or mild discomfort; no limitation in activity; no medical 
intervention/therapy required

Grade 2 = Moderate – mild to moderate limitation in activity, some assistance may be 
needed; no or minimal medical intervention/therapy required

Grade 3 = Severe – marked limitation in activity, some assistance usually required; 
medical intervention/therapy required, hospitalization is possible

Grade 4 = Life-threatening – extreme limitation in activity, significant assistance 
required; significant medical intervention/therapy required, hospitalization or hospice 
care probable

Grade 5 = Death - the event results in death
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The term “severe” is often used to describe the intensity of a specific event (as in mild, moderate 
or severe myocardial infarction); the event itself, however, may be of relatively minor medical 
significance (such as severe headache). This criterion is not the same as “serious” which is based 
on subject/event outcome or action criteria associated with events that pose a threat to a subject’s 
life or functioning.
Seriousness, not severity, serves as a guide for defining regulatory obligations.
10.2.3.
Causality
The Investigator must determine the relationship between the administration of the LD 
chemotherapy, JCAR017 or the combination agent and the occurrence of an AE/SAE as Not 
Suspected or Suspected as defined below:
Not suspected:
a causal relationship of the adverse event to IP administration is 
unlikely or remote, or other medications, therapeutic 
interventions, or underlying conditions provide a sufficient 
explanation for the observed event.
Suspected:
there is a reasonable possibility that the administration of IP 
caused the adverse event. ‘Reasonable possibility’ means there 
is evidence to suggest a causal relationship between the IP and 
the adverse event.
Causality should be assessed and provided for every AE/SAE based on currently available 
information. Causality is to be reassessed and provided as additional information becomes 
available.
If an event is assessed as suspected of being related to a comparator, ancillary or additional IP 
that has not been manufactured or provided by Celgene, please provide the name of the 
manufacturer when reporting the event.
10.2.4.
Duration
For both AEs and SAEs, the Investigator will provide a record of the start and stop dates of the 
event.
10.2.5.
Action Taken
The Investigator will report the action taken with IP as a result of an AE or SAE, as applicable 
(eg, discontinuation, interruption, or dose reduction of IP, as appropriate) and report if 
concomitant and/or additional treatments were given for the event. 
10.2.6.
Outcome
The Investigator will report the outcome of the event for both AEs and SAEs.
Serious adverse events will be followed until they return to baseline, the event stabilizes or is no
longer considered clinically significant by the Investigator; the subject dies or withdraws
consent; or study closure.
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10.3.
Abnormal Laboratory Values
An abnormal laboratory value is considered to be an AE if the abnormality:

results in discontinuation from the study;

requires treatment, modification/ interruption of IP dose, or any other therapeutic 
intervention; or

is judged to be of significant clinical importance, eg, one that indicates a new disease 
process and/or organ toxicity, or is an exacerbation or worsening of an existing 
condition.
Regardless of severity grade, only laboratory abnormalities that fulfill a seriousness criterion 
need to be documented as a serious adverse event.
If a laboratory abnormality is one component of a diagnosis or syndrome, then only the diagnosis 
or syndrome should be recorded on the AE page/screen of the CRF. If the abnormality was not a 
part of a diagnosis or syndrome, then the laboratory abnormality should be recorded as the AE. If 
possible, the laboratory abnormality should be recorded as a medical term and not simply as an 
abnormal laboratory result (eg, record thrombocytopenia rather than decreased platelets).
10.4.
Pregnancy
All pregnancies and suspected pregnancies (including elevated βhCG or positive pregnancy test) 
occurring at any time after receipt of lymphodepleting chemotherapy or infusion of JCAR017 in 
either a female subject of childbearing potential or a partner of childbearing potential of a male 
subject are immediately reportable events. 
Additionally pregnancies and suspected pregnancies in either a female subject of childbearing 
potential or a partner of childbearing potential of a male subject that occur while the subject is 
receiving IP, or within 3 months of the last dose of durvalumab, or within 28 days after the last 
dose of CC-122, CC-220, ibrutinib or CC-99282, or 24 weeks after the last dose of nivolumab or 
relatlimab, are considered immediately reportable events. Investigational product is to be 
discontinued immediately. 
The pregnancy, suspected pregnancy, or positive pregnancy test must be reported to Celgene 
Drug Safety immediately by email, phone or facsimile, or other appropriate method, using the 
Pregnancy Initial Report Form, or approved equivalent form.
10.4.1.
Females of Childbearing Potential
In case of pregnancies and suspected pregnancies in female subjects, the Investigator will follow 
the subject until completion of the pregnancy and afterwards up to 1 year of the newborn baby, 
and must notify Celgene Drug Safety immediately about the outcome of the pregnancy (either 
normal or abnormal outcome) using the Pregnancy Follow-up Report Form, or approved 
equivalent form.
If the outcome of the pregnancy was abnormal (eg, spontaneous abortion), the Investigator 
should report the abnormal outcome as an AE. If the abnormal outcome meets any of the serious 
criteria, it must be reported as an SAE to Celgene Drug Safety by facsimile, or other appropriate 
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as individual SAEs. Any other AEs leading to death should be reported as an SAE according to 
Table 31.
10.6.
Potential Risks and Management of Treatment Toxicities
A summary of potential risks and management of treatment toxicity is provided below. See the 
respective IB (US PI for Arm D) for a complete discussion of potential risks associated with 
JCAR017 and combination agent.
10.6.1.
Management of Toxicities Associated with JCAR017
Cytokine release syndrome (CRS) and neurologic toxicities (NT) are associated with CAR T cell 
therapies. Celgene has developed specific toxicity management guidelines (TMG) for CRS and 
NT associated with Celgene cellular products based on current clinical experience across the 
clinical development programs (Appendix M). These recommendations are based on the CRS 
revised grading system (Lee, 2014) and the Common Toxicity Criteria for Adverse Events 
(CTCAE) and need to be used for grading of CRS and NT to guide management in this trial. 
If available and adopted as per site standard practice, CRS and NT grading according to the 
American Society for Transplantation and Cellular Therapy (ASTCT) Consensus Grading 
System (Lee, 2019) should also be recorded in the eCRF to inform future modifications of the 
management guidelines.
10.6.1.1.
Cytokine Release Syndrome
Administration of JCAR017 is associated with cytokine release syndrome (CRS). Cytokine release 
syndrome is characterized by high fever, fatigue, nausea, headache, dyspnea, tachycardia, rigors, 
hypotension, hypoxia, myalgia/arthralgia, and anorexia. Clinical symptoms and severity of CRS 
are highly variable (Lee, 2014), and management can be complicated by concurrent conditions.
With JCAR017, CRS usually occurs within two weeks after infusion (Abramson, 2017).

Fever, especially high fever (≥ 38.5°C or ≥ 101.3°F), is a commonly-observed 
hallmark of CRS, and many features of CRS mimic infection. Hence, infection must 
be considered in all subjects presenting with CRS symptoms and appropriate cultures 
must be obtained and empiric antibiotic therapy initiated per institution standard of 
care.

Less common symptoms associated with CRS include cardiac dysfunction, adult 
respiratory distress syndrome, renal and/or hepatic failure, coagulopathies, 
disseminated intravascular coagulation, and capillary leak syndrome. 

Neurologic toxicity has been observed concurrently with CRS. 

With CAR T cell products, CRS has been reported in a few cases to be associated 
with findings of macrophage activation syndrome/hemophagocytic 
lymphohistiocytosis (MAS/HLH), and the physiology of the syndromes may overlap. 
Please refer to Appendix M for detailed description of CRS, grading and treatment 
recommendations.
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10.6.1.2.
Fever
The possibility of CRS should be considered for all subjects with fever (≥ 38°C or ≥ 100.4°F) 
following JCAR017 treatment. Subjects should be monitored closely for hemodynamic 
instability and changing neurologic status. Febrile subjects, neutropenic or otherwise, should be 
evaluated promptly for infection and managed per institutional or standard clinical practice.
10.6.1.3.
Cytopenias
Severe cytopenias, including anemia, leukopenia, neutropenia, and thrombocytopenia, can occur 
with both JCAR017 and lymphodepleting chemotherapy, and delayed recovery has been 
observed. Complete blood counts should be monitored after JCAR017 infusion until count 
recovery. Institutional guidelines should be followed in the event of Grade ≥ 3 cytopenias.
10.6.1.4.
Infections
Life-threatening and fatal infections have been observed. Severe infections, may include 
bacterial, fungal (including pneumocystis jirovecii), and viral infections (eg, cytomegalovirus 
[CMV], hepatitis B virus [HBV], respiratory viruses and other viruses). A high index of 
suspicion is warranted in the event of prolonged or recurrent cytopenias, especially in 
conjunction with hypogammaglobulinemia, severe lymphopenia, and/or recent use of 
corticosteroids. Viral reactivation and other serious opportunistic infections should be considered 
in these settings, and prophylactic, pre-emptive, or symptomatic treatment with antimicrobial, 
antifungal, anti-pneumocystic, and/or antiviral therapies should be considered per local 
institutional guidelines.
10.6.1.5.
Neurologic Toxicities
CAR T cell therapy is associated with unique neurologic toxicities. Neurologic symptoms may 
include altered mental status, aphasia, altered level of consciousness, and seizures or seizure-like 
activity. With JCAR017, to date, the start of neurologic symptoms has been noted between 3 to 
23 days (median 10 days) (Abramson, 2017) after CAR T cell infusion and in severe cases may 
require admission to the intensive care unit (ICU) for frequent monitoring, respiratory support, or 
intubation for airway protection. The symptoms are variable generally occur as CRS is resolving 
or after CRS resolution.
Please refer to Appendix M for detailed description of neurologic toxicities, grading and 
treatment recommendations.
10.6.1.6.
Macrophage Activation Syndrome
Macrophage activation syndrome (MAS) is a serious disorder potentially associated with 
uncontrolled activation and proliferation of CAR T cells and subsequent activation of 
macrophages. MAS is typically characterized by high-grade, non-remitting fever, cytopenias, 
and hepatosplenomegaly. Laboratory abnormalities found in MAS include elevated 
inflammatory cytokine levels, serum ferritin, soluble IL-2 receptor (sCD25), triglycerides, and 
decreased circulating NK cells. Other findings include variable levels of transaminases, signs of 
acute liver failure, coagulopathy, and disseminated intravascular coagulopathy. There are no 
definitive diagnostic criteria for MAS; it is typically diagnosed using published criteria for 
hemophagocytic lymphohistiocytosis (Schulert, 2015). While there is considerable overlap in 
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clinical manifestations and laboratory findings between MAS and CRS, other distinguishing 
MAS physical findings such as hepatosplenomegaly and lymphadenopathy are not common in 
adult subjects treated with activated T cell therapies.
Subjects treated with JCAR017 should be monitored for MAS, and cytokine-directed therapy 
should be considered as clinically indicated.
10.6.1.7.
Infusion Reactions
Administration of JCAR017 may cause infusion reactions, such as fever, rigors, rash, urticaria, 
dyspnea, hypotension, and/or nausea.
To minimize the risk of infusion reactions, all subjects should be pre-medicated with 
acetaminophen and diphenhydramine. Mild infusion reactions should be managed expectantly 
with antipyretics, antihistamines, and anti-emetics. Corticosteroids should be avoided because of 
the potential impact on efficacy of infused JCAR017 cells. 
The following guidelines should be followed for infusion reactions:

Grade 1: administer symptomatic treatment; continue JCAR017 administration of 
both CD8+ and CD4+ components at the same dose and rate 

Grade 2: stop administration of JCAR017; administer symptomatic treatment, and 
resume JCAR017 administration of both CD8+ and CD4+ components at a reduced 
rate of administration only after symptoms resolution

Grade 3: stop administration of JCAR017, administer symptomatic treatment, and 
resume at a reduced rate of administration only after symptoms resolve. If Grade 3 
reaction recurs, discontinue JCAR017 administration; no further CD8+ or CD4+ 
components of JCAR017 should be administered

Grade 4: discontinue administration of JCAR017 and administer symptomatic 
treatment as necessary; no further no further CD8+ or CD4+ components of 
JCAR017 should be administered
10.6.1.8.
Tumor Lysis Syndrome
Both lymphodepleting chemotherapy and JCAR017 may cause tumor lysis syndrome (TLS) in 
subjects with high disease burden. Subjects should be closely monitored for laboratory evidence 
of TLS (hyperuricemia, hyperkalemia, hyperphosphatemia, and hypocalcemia) (see 
Appendix L), and subjects at high risk for developing TLS, such as those with high disease 
burden and high cell turnover, should receive prophylactic treatment including administration of 
allopurinol and hydration, per standard clinical practice.
10.6.1.9.
B-cell Aplasia
B-cell aplasia is an expected potential off-tumor, on-target toxicity. Prolonged B-cell aplasia has 
been observed in other CD19-directed CAR T cell programs (Davila, 2013; Grupp, 2013). Serum 
immunoglobulin levels will be obtained from all subjects prior to and at various time points 
following JCAR017 treatment. Hypogammaglobulinemic subjects (serum immunoglobulin G 
(IgG) < 500 mg/dL) should be considered for intravenous immunoglobulin replacement therapy 
per institutional guidelines.
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10.6.3.
Risks Associated with Durvalumab
Based on the mechanism of action of durvalumab leading to T cell activation and proliferation, 
there is the possibility of observing irAEs during the conduct of this study for subjects treated in 
Arm A. Potential irAEs may be similar to those seen with the use of ipilimumab, nivolumab 
(BMS-936558), and BMS-936559 and may include immune-mediated enterocolitis, dermatitis, 
hepatitis, endocrinopathies, vasculitis, non-infectious meningitis and non-infectious encephalitis
(Hodi, 2010; Brahmer, 2012; Topalian, 2013). Subjects should be monitored for signs and 
symptoms of irAEs. In the absence of an alternate etiology (eg, infection or disease progression), 
an immune-related etiology should be considered for signs or symptoms of enterocolitis, 
dermatitis, hepatitis, and endocrinopathy.
In addition to the dose modifications shown in Appendix C, it is recommended that management 
of irAEs follow the guidelines outlined for ipilimumab (Weber, 2012). These guidelines 
recommend the following:

Subjects should be evaluated to identify any alternative etiology

In the absence of clear alternative etiology, all events of an inflammatory nature 
should be considered to be immune-related

Symptomatic and topical therapy should be considered for low-grade events

Systemic corticosteroids should be considered for a persistent low-grade event or for 
a severe event

More potent immunosuppressives should be considered for events not responding to 
systemic steroids (eg, infliximab, mycophenolate, etc).
If the investigator has any question in regard to an AE being an irAE, the investigator should 
immediately contact the Sponsor’s medical monitor.
Dose modifications (ie, dose interruption, dose hold, or infusion rate modification) of 
durvalumab may be required in the event of treatment related toxicity. See Appendix C,
Appendix D and Appendix E for detailed instructions for durvalumab dose modifications and 
toxicity management.
Administration of durvalumab may cause infusion reactions, such as fever, rigors, rash, urticaria, 
dyspnea, hypotension, and/or nausea.
To minimize the risk of infusion reactions, all subjects should be pre-medicated with 
acetaminophen and diphenhydramine. Mild infusion reactions should be managed expectantly 
with antipyretics, antihistamines, and anti-emetics. Rigors may be treated with meperidine. 
The following guidelines should be followed for infusion reactions:

Grade 1: administer symptomatic treatment; continue durvalumab administration at 
the same dose and rate

Grade 2: stop administration of durvalumab; administer symptomatic treatment, and 
resume durvalumab administration at a reduced rate of administration only after 
symptoms resolution
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
Grade 3: stop administration of durvalumab, administer symptomatic treatment, and 
resume at a reduced rate of administration only after symptoms resolve. If Grade 3 
reaction recurs, discontinue durvalumab administration 

Grade 4: discontinue administration of durvalumab and administer symptomatic 
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10.6.6.
Risks Associated with Ibrutinib
10.6.6.1.
Hemorrhage
Fatal bleeding events have occurred in subjects treated with ibrutinib. The mechanism for the 
bleeding events is not well understood. Ibrutinib may increase the risk of hemorrhage in subjects 
receiving antiplatelet or anticoagulant therapies and subjects should be monitored for signs of 
bleeding.
Consider the benefit-risk of withholding ibrutinib for at least 3 to 7 days pre and post-surgery 
depending upon the type of surgery and the risk of bleeding. 
10.6.6.2.
Infections
Fatal and non-fatal infections (including bacterial, viral, or fungal) have occurred with ibrutinib 
therapy. Cases of progressive multifocal leukoencephalopathy (PML) and pneumocystis jirovecii
pneumonia (PJP) have occurred in subjects treated with ibrutinib. Prophylaxis should be 
considered according to standard of care in subjects who are at increased risk for opportunistic 
infections. Subjects should be monitored and evaluated for fever and infections and treated
appropriately.
10.6.6.3.
Cytopenias
Treatment-emergent Grade 3 or 4 cytopenias including neutropenia, thrombocytopenia, and 
anemia based on laboratory measurements occurred in subjects with B-cell malignancies treated 
with single agent ibrutinib. Subjects should be monitored monthly with complete blood counts.
10.6.6.4.
Cardiac Arrhythmias
Fatal and serious cardiac arrhythmias (ventricular tachyarrhythmias, atrial fibrillation and atrial 
flutter) have occurred with ibrutinib therapy. These events have occurred particularly in subjects 
with cardiac risk factors, hypertension, acute infections, and a previous history of cardiac 
arrhythmias.
Subjects should be periodically monitored clinically for cardiac arrhythmias. An ECG should be
performed for subjects who develop arrhythmic symptoms (eg, palpitations, lightheadedness, 
syncope, chest pain) or new onset dyspnea. Cardiac arrhythmias should be managed 
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appropriately, and if it persists, consider the risks and benefits of ibrutinib treatment and follow 
dose modification guidelines.
10.6.6.5.
Hypertension
Hypertension has occurred in subjects treated with ibrutinib with a median time to onset of 
4.6 months. Subjects should be monitored for new onset hypertension or hypertension that is not 
adequately controlled after starting ibrutinib. Existing anti-hypertensive medications should be 
adjusted and/or anti-hypertensive treatment initiated as appropriate.
10.6.6.6.
Tumor Lysis Syndrome
Tumor lysis syndrome has been infrequently reported with ibrutinib therapy. Assess the baseline 
risk (eg, high tumor burden) and take appropriate precautions. Subjects should be monitored 
closely and treated as appropriate.
10.6.6.7.
Embryo-Fetal Toxicity
Based on findings in animals, ibrutinib can cause fetal harm when administered to a pregnant 
woman. Administration of ibrutinib to pregnant rats and rabbits during the period of 
organogenesis caused embryo-fetal toxicity including malformations at exposures that were 
2-20 times higher than those reported in subjects with hematologic malignancies. Women should 
avoid becoming pregnant while taking ibrutinib and for 1 month after stopping the treatment. If 
ibrutinib is used during pregnancy or if the subject becomes pregnant while taking ibrutinib, the 
subject should be apprised of the potential hazard to a fetus.
For a comprehensive list of risks of ibrutinib refer to the package insert.
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10.6.7.2.
Clinical Safety of Nivolumab Monotherapy
Overall, the safety profile of nivolumab monotherapy is manageable and generally consistent 
across completed and ongoing clinical trials with no MTD reached at any dose tested up to 10 
mg/kg. Most AEs were low-grade (Grade 1 to 2) with relatively few related high-grade (Grade 3 
to 4) AEs. There was no pattern in the incidence, severity, or causality of AEs with respect to 
nivolumab dose level.
Additional details on the safety profile of nivolumab, including results from other clinical 
studies, are also available in the nivolumab IB.
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10.6.7.5.
Complications of Allogeneic Hematopoietic Stem Cell Transplantation
Complications of allogeneic HSCT after treatment with PD-1/PD-L1 inhibitors including 
nivolumab, administered before allogeneic HSCT, may be associated with an increased risk of 
transplant-related complications, including GVHD. Fatal cases have been reported in clinical 
studies. Study subjects who receive allogeneic HSCT after relatlimab and/or nivolumab should 
be monitored closely for early evidence of transplant-related complications and prompt 
interventions should be implemented. 
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10.7.
Expedited Reporting of Adverse Events
For the purpose of regulatory reporting, Celgene Drug Safety will determine the expectedness of 
events suspected of being related to JCAR017, or to the combination agent based on the 
respective IBs for durvalumab, CC-122, CC-220, CC-99282, nivolumab, relatlimab, or PI for 
ibrutinib.
In the United States, all suspected unexpected serious adverse reactions (SUSARs) will be 
reported in an expedited manner in accordance with 21 CFR 312.32.
For countries within the European Economic Area (EEA), Celgene or its authorized 
representative will report in an expedited manner to Regulatory Authorities and Ethics 
Committees concerned, suspected unexpected serious adverse reactions (SUSARs) in accordance 
with Directive 2001/20/EC and the Detailed Guidance on collection, verification and 
presentation of adverse reaction reports arising from clinical trials on investigational products for 
human use (ENTR/CT3) and also in accordance with country-specific requirements.
Celgene or its authorized representative shall notify the Investigator of the following 
information: 
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11.
DISCONTINUATIONS
11.1.
Treatment Discontinuation
The following events are considered sufficient reasons for discontinuing a subject from the 
investigational product(s):

Adverse event

Withdrawal by subject

Death

Lost to follow-up

Other (to be specified on the CRF)
The reason for discontinuation of treatment should be recorded in the CRF and in the source 
documents.
The decision to discontinue a subject from treatment remains the responsibility of the treating 
physician, which will not be delayed or refused by the Sponsor. However, prior to discontinuing 
a subject, the Investigator may contact the Medical Monitor and forward appropriate supporting 
documents for review and discussion.
11.2.
Study Discontinuation
The following events are considered sufficient reasons for discontinuing a subject from the 
study:

Screen failure

Adverse event

Manufacturing failure

Withdrawal by subject

Death

Lost to follow-up

Other (to be specified on the CRF)
The reason for study discontinuation should be recorded in the CRF and in the source 
documents.
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12.
EMERGENCY PROCEDURES
12.1.
Emergency Contact
In emergency situations, the Investigator should contact the responsible Clinical Research 
Physician/Medical Monitor or designee by telephone at the number(s) listed on the Emergency 
Contact Information page of the protocol (after title page).
In the unlikely event that the Clinical Research Physician/Medical Monitor or designee cannot be 
reached, please contact the global Emergency Call Center by telephone at the number listed on 
the Emergency Contact Information page of the protocol (after title page). This global 
Emergency Call Center is available 24 hours a day and 7 days a week. The representatives are 
responsible for obtaining your call-back information and contacting the on-call Celgene/contract 
research organization Medical Monitor, who will then contact you promptly.
Note: The back-up 24-hour global emergency contact call center should only be used if you are 
not able to reach the Clinical Research Physician(s) or Medical Monitor or designee for 
emergency calls. 
12.2.
Emergency Identification of Investigational Products
This is an open-label study; therefore, IP will be identified on the package labeling.
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13.
REGULATORY CONSIDERATIONS
13.1.
Good Clinical Practice
The procedures set out in this study protocol pertaining to the conduct, evaluation, and 
documentation of this study are designed to ensure that Celgene, its authorized representative, 
and Investigator abide by Good Clinical Practice (GCP), as described in International Council for 
Harmonisation (ICH) Guideline E6 and in accordance with the general ethical principles outlined 
in the Declaration of Helsinki. The study will receive approval from an IRB/EC prior to 
commencement. The Investigator will conduct all aspects of this study in accordance with 
applicable national, state, and local laws of the pertinent regulatory authorities.
13.2.
Investigator Responsibilities
Investigator responsibilities are set out in the ICH Guideline for Good Clinical Practice and in 
the local regulations. Celgene staff or an authorized representative will evaluate and approve all 
Investigators who in turn will select their staff.
The Investigator should ensure that all persons assisting with the study are adequately informed 
about the protocol, amendments, study treatments, as well as study-related duties and functions, 
including obligations of confidentiality of Celgene information. The Investigator should maintain 
a list of Sub-investigators and other appropriately qualified persons to whom he or she has 
delegated significant study-related duties.
The Investigator is responsible for keeping a record of all subjects who sign an informed consent 
form (ICF) and are screened for entry into the study. Subjects who fail screening must have the 
reason(s) recorded in the subject’s source documents.
The Investigator, or a designated member of the Investigator’s staff, must be available during 
monitoring visits to review data, resolve queries and allow direct access to subject records (eg, 
medical records, office charts, hospital charts, and study-related charts) for source data 
verification. The Investigator must ensure timely and accurate completion of CRFs and queries.
The information contained in the protocol and amendments (with the exception of the 
information provided by Celgene on public registry websites) is considered Celgene confidential 
information. Only information that is previously disclosed by Celgene on a public registry 
website may be freely disclosed by the Investigator or its institution, or as outlined in the Clinical 
Trial Agreement. Celgene protocol, amendment and IB information is not to be made publicly 
available (for example on the Investigator’s or their institution’s website) without express written 
approval from Celgene. Information proposed for posting on the Investigator’s or their 
institution’s website must be submitted to Celgene for review and approval, providing at least 5 
business days for review.
At the time results of this study are made available to the public, Celgene will provide 
Investigators with a summary of the results that is written for the lay person. The Investigator is 
responsible for sharing these results with the subject and/or their caregiver as agreed by the 
subject.
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13.3.
Subject Information and Informed Consent
The Investigator must obtain informed consent of a subject and/or a subject’s legal representative 
prior to any study related procedures.
Documentation that informed consent occurred prior to the study subject’s entry into the study 
and of the informed consent process should be recorded in the study subject’s source documents 
including the date. The original ICF signed and dated by the study subject and by the person 
consenting the study subject prior to the study subject’s entry into the study, must be maintained 
in the Investigator’s study files and a copy given to the study subject. In addition, if a protocol is 
amended and it impacts on the content of the informed consent, the ICF must be revised. Study 
subjects participating in the study when the amended protocol is implemented must be re-
consented with the revised version of the ICF. The revised ICF signed and dated by the study 
subject and by the person consenting the study subject must be maintained in the Investigator’s 
study files and a copy given to the study subject.
13.4.
Confidentiality
Celgene affirms the subject's right to protection against invasion of privacy and to be in 
compliance with ICH and other local regulations (whichever is most stringent). Celgene requires 
the Investigator to permit Celgene's representatives and, when necessary, representatives from 
regulatory authorities, to review and/or copy any medical records relevant to the study in 
accordance with local laws.
Should direct access to medical records require a waiver or authorization separate from the 
subject’s signed ICF, it is the responsibility of the Investigator to obtain such permission in 
writing from the appropriate individual.
13.5.
Protocol Amendments
Any amendment to this protocol must be approved by the Celgene Clinical Research 
Physician/Medical Monitor. Amendments will be submitted to the IRB/EC for written approval.
Written approval must be obtained before implementation of the amended version occurs. The 
written signed approval from the IRB/EC should specifically reference the Investigator name, 
protocol number, study title and amendment number(s) that is applicable. Amendments that are 
administrative in nature do not require IRB/IEC approval but will be submitted to the IRB/IEC 
for information purposes.
13.6.
Institutional Review Board/Independent Ethics Committee Review 
and Approval
Before the start of the study, the study protocol, ICF, and any other appropriate documents will 
be submitted to the IRB/EC with a cover letter or a form listing the documents submitted, their 
dates of issue, and the site (or region or area of jurisdiction, as applicable) for which approval is 
sought. If applicable, the documents will also be submitted to the authorities in accordance with 
local legal requirements.
IP can only be supplied to an Investigator by Celgene or its authorized representative after 
documentation on all ethical and legal requirements for starting the study has been received by 
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Celgene or its authorized representative. This documentation must also include a list of the 
members of the IRB/EC and their occupation and qualifications. If the IRB/EC will not disclose 
the names, occupations and qualifications of the committee members, it should be asked to issue 
a statement confirming that the composition of the committee is in accordance with GCP. For 
example, the IRB General Assurance Number may be accepted as a substitute for this list. 
Formal approval by the IRB/EC should mention the protocol title, number, amendment number 
(if applicable), study site (or region or area of jurisdiction, as applicable), and any other 
documents reviewed. It must mention the date on which the decision was made and must be 
officially signed by a committee member. Before the first subject is enrolled in the study, all 
ethical and legal requirements must be met.
The IRB/EC and, if applicable, the authorities, must be informed of all subsequent protocol 
amendments in accordance with local legal requirements. Amendments must be evaluated to 
determine whether formal approval must be sought and whether the ICF should also be revised.
The Investigator must keep a record of all communication with the IRB/EC and, if applicable, 
between a Coordinating Investigator and the IRB/EC. This statement also applies to any 
communication between the Investigator (or Coordinating Investigator, if applicable) and 
regulatory authorities.
Any advertisements used to recruit subjects for the study must be reviewed by Celgene and the 
IRB/EC prior to use.
13.7.
Ongoing Information for Institutional Review Board/ Ethics 
Committee
If required by legislation or the IRB/EC, the Investigator must submit to the IRB/EC:

Information on serious or unexpected adverse events as soon as possible; 

Periodic reports on the progress of the study;

Deviations from the protocol or anything that may involve added risk to subjects.
13.8.
Termination of the Study
Celgene reserves the right to terminate this study prematurely at any time for reasonable medical 
or administrative reasons. Any premature discontinuation will be appropriately documented 
according to local requirements (eg, IRB/EC, regulatory authorities, etc).
In addition, the Investigator or Celgene has the right to discontinue a single site at any time 
during the study for medical or administrative reasons such as:

Unsatisfactory enrollment;

GCP noncompliance;

Inaccurate or incomplete data collection;

Falsification of records;

Failure to adhere to the study protocol.
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14.
DATA HANDLING AND RECORDKEEPING 
14.1.
Data/Documents
The Investigator must ensure that the records and documents pertaining to the conduct of the 
study and the distribution of the investigational product are complete, accurate, filed and 
retained. Examples of source documents include: hospital records; clinic and office charts; 
laboratory notes; memoranda; subject’s diaries or evaluation checklists; dispensing records; 
recorded data from automated instruments; copies or transcriptions certified after verification as 
being accurate copies; microfiche; x-ray film and reports; and records kept at the pharmacy, and 
the laboratories, as well as copies of CRFs or CD-ROM.
14.2.
Data Management
Data will be collected via CRF and entered into the clinical database per Celgene standard 
operating procedures (SOPs). These data will be electronically verified through use of 
programmed edit checks specified by the clinical team. Discrepancies in the data will be brought 
to the attention of the clinical team, and investigational site personnel, if necessary. Resolutions 
to these issues will be reflected in the database. An audit trail within the system will track all 
changes made to the data.
14.3.
Record Retention
Essential documents must be retained by the Investigator according to the period of time outlined 
in the clinical trial agreement. The Investigator must retain these documents for the time period 
described above or according to local laws or requirements, whichever is longer. Essential 
documents include, but are not limited to, the following:

Signed ICFs for all subjects;

Subject identification code list, screening log (if applicable), and enrollment log;

Record of all communications between the Investigator and the IRB/EC;

Composition of the IRB/EC;

Record of all communications between the Investigator, Celgene, and their authorized 
representative(s);

List of Sub-investigators and other appropriately qualified persons to whom the 
Investigator has delegated significant study-related duties, together with their roles in 
the study, curriculum vitae, and their signatures;

Copies of CRFs (if paper) and of documentation of corrections for all subjects;

IP accountability records;

Record of any body fluids or tissue samples retained;

All other source documents (subject records, hospital records, laboratory records, 
etc.); 
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
All other documents as listed in Section 8 of the ICH consolidated guideline on GCP 
(Essential Documents for the Conduct of a Clinical Trial).
The Investigator must notify Celgene if he/she wishes to assign the essential documents to 
someone else, remove them to another location or is unable to retain them for a specified period.
The Investigator must obtain approval in writing from Celgene prior to destruction of any 
records. If the Investigator is unable to meet this obligation, the Investigator must ask Celgene 
for permission to make alternative arrangements. Details of these arrangements should be 
documented. 
All study documents should be made available if required by relevant health authorities. 
Investigator or institution should take measures to prevent accidental or premature destruction of 
these documents.
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15.
QUALITY CONTROL AND QUALITY ASSURANCE
All aspects of the study will be carefully monitored by Celgene or its authorized representative 
for compliance with applicable government regulations with respect to current GCP and SOPs.
15.1.
Study Monitoring and Source Data Verification
Celgene ensures that appropriate monitoring procedures are performed before, during and after 
the study. All aspects of the study are reviewed with the Investigator and the staff at a study 
initiation visit and/or at an Investigators’ Meeting. Prior to enrolling subjects into the study, a 
Celgene representative will review the protocol, CRFs, procedures for obtaining informed 
consent, record keeping, and reporting of AEs/SAEs with the Investigator. Monitoring will 
include on-site visits with the Investigator and his/her staff as well as any appropriate 
communications by mail, email, fax, or telephone. During monitoring visits, the facilities, 
investigational product storage area, CRFs, subject’s source documents, and all other study 
documentation will be inspected/reviewed by the Celgene representative in accordance with the 
Study Monitoring Plan.
Accuracy will be checked by performing source data verification that is a direct comparison of 
the entries made onto the CRFs against the appropriate source documentation. Any resulting 
discrepancies will be reviewed with the Investigator and/or his/her staff. Any necessary 
corrections will be made directly to the CRFs or via queries by the Investigator and/or his/her 
staff. Monitoring procedures require that informed consents, adherence to inclusion/exclusion 
criteria and documentation of SAEs and their proper recording be verified. Additional 
monitoring activities may be outlined in a study-specific monitoring plan.
15.2.
Audits and Inspections
In addition to the routine monitoring procedures, a Good Clinical Practice Quality Assurance 
unit exists within Celgene. Representatives of this unit will conduct audits of clinical research 
activities in accordance with Celgene SOPs to evaluate compliance with Good Clinical Practice 
guidelines and regulations.
The Investigator is required to permit direct access to the facilities where the study took place, 
source documents, CRFs and applicable supporting records of study subject participation for 
audits and inspections by IRB/ECs, regulatory authorities (eg, Food and Drug Administration 
(FDA), European Medicines Agency (EMA), Health Canada) and company authorized 
representatives. The Investigator should make every effort to be available for the audits and/or 
inspections. If the Investigator is contacted by any regulatory authority regarding an inspection, 
he/she should contact Celgene immediately.
15.3.
Product Quality Compliant
A Product Quality Complaint (PQC) is any written, electronic, or oral communication that 
alleges deficiencies related to the identity, quality, durability, reliability, safety, effectiveness, 
purity, or performance of any drug product manufactured by or on behalf of Celgene Corporation 
after it is released for distribution. Product Quality Complaints may reduce the usability of the 
product for its intended function or affect performance of the product and therefore pose a 
significant risk to the subject. Examples of PQCs include (but are not limited to): mixed product, 
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16.
PUBLICATIONS
As described in Section 13.2, all protocol- and amendment-related information, with the 
exception of the information provided by Celgene on public registry websites, is considered 
Celgene confidential information and is not to be used in any publications. Celgene protocol-
related information proposed for use in a publication must be submitted to Celgene for review 
and approval, and should not be utilized in a publication without express written approval from 
Celgene, or as described in the Clinical Trial Agreement.
Celgene will ensure Celgene-sponsored studies are considered for publication in the scientific 
literature in a peer-reviewed journal, irrespective of the results. At a minimum, this applies to 
results from all Phase 3 clinical studies, and any other study results of significant medical 
importance. This also includes results relating to investigational medicines whose development 
programs have been discontinued.
Study results may also be presented at one or more medical congresses, and may be used for 
scientific exchange and teaching purposes. Additionally, this study and its results may be 
submitted for inclusion in all appropriate health authority study registries, as well as publication 
on health authority study registry websites, as required by local health authority regulations.
Eligibility for external authorship, as well as selection of first authorship, will be based on 
several considerations, including, but not limited to, contribution to protocol development, study 
recruitment, data quality, participation in data analysis, participation in study steering committee 
(when applicable) and contribution to abstract, presentation and/or publication development.
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Fraietta JA, Nobles CL, Sammons MA, Lundh S, Carty SA, Reich TJ, et al. Disruption of TET2 
promotes the therapeutic efficacy of CD19-targeted T cells. Nature. 2018a Jun;558(7709):307-
12.
Fraietta JA, Beckwith KA, Patel PR, Ruella M, Zheng Z, Barrett, DM et al. Ibrutinib enhances 
chimeric antigen receptor T-cell engraftment and efficacy in leukemia. Blood. 2016; 127 :1117-
27.
Gandhi AK, Kang J, Havens CG, Conklin T, Ning Y, Wu L, et al. Immunomodulatory agents 
lenalidomide and pomalidomide co-stimulate T cells by inducing degradation of T cell repressors 
Ikaros and Aiolos via modulation of the E3 ubiquitin ligase complex CRL4(CRBN). Br J 
Haematol. 2014 Mar;164(6):811-21. 
Gandhi AK, Mendy D, Parton A, Wu L, Kosek J, Zhang LH, et al. CC-122 is a novel pleiotropic 
pathway modifier with potent in vitro immunomodulatory and anti-angiogenic properties and in 
vivo anti-tumor activity in hematological cancers. Blood. 2012;120:2963.
Garcia-Diaz A, Shin DS, Moreno BH, Saco J, Escuin-Ordinas H, Rodriguez GA, et al. Interferon 
Receptor Signaling Pathways Regulating PD-L1 and PD-L2 Expression. Cell Rep. 2017 May 
9;19(6):1189-1201.
Gardner RA, Finney O, Annesley C, Brakke H, Summers C, Leger K, et al. Intent-to-treat 
leukemia remission by CD19 CAR T cells of defined formulation and dose in children and 
young adults. Blood. 2017 Jun 22;129(25):3322-3331. 
Gauthier J, Hirayama AV, Hay KA, Li D, Lymp J, Sheih A. Comparison of efficacy and toxicity 
of CD19-specific chimeric antigen receptor T-cells alone or in combination with ibrutinib for 
relapsed and/or refractory CLL. Blood. 2018;132:299.
Gill SI, Vides V, Frey NV, Metzger S, O'Brien M, Hexner E, et al. Prospective clinical trial of 
anti-CD19 CAR T cells in combination with ibrutinib for the treatment of chronic lymphocytic 
leukemia shows a high response rate. Blood. 2018;132:298.
Grupp SA, Kalos M, Barrett D, Aplenc R, Porter DL, Rheingold SR, et al. Chimeric antigen 
receptor-modified T cells for acute lymphoid leukemia. N Engl J Med. 2013 Apr 
18;368(16):1509-18.
Gunderson AJ, Kaneda MM, Tsujikawa T, Nguyen AV, Affara NI, Ruffell B, et al. Bruton 
kinase-dependent immune cell cross-talk drives pancreas cancer. Cancer Discov 2016; 6: 270-85.
Gust J, Hay KA, Hanafi L-A, Li D, Myerson D, Gonzalez-Cuyar LF, et al. Endothelial activation 
and blood–brain barrier disruption in neurotoxicity after adoptive immunotherapy with CD19 
CAR-T cells. Cancer Disc. 2017 Oct; doi: 10.1158/2159-8290.CD-17-0698.
Haanen JBAG, Carbonnel F, Robert C, Kerr KM, Peters S, Larkin J, et al. Management of 
toxicities from immunotherapy: ESMO clinical practice guidelines for diagnosis, treatment and 
follow-up. Annals of Oncology. 2017 Jan 01; 28:iv119-iv142.
Hacein-Bey-Abina S, Von Kalle C, Schmidt M, McCormack MP, Wulffraat N, Leboulch P, et al. 
LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1. 
Science. 2003 Oct 17;302(5644):415-9.
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18.
APPENDICES
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APPENDIX A. TABLE OF ABBREVIATIONS
Table 33:
Abbreviations and Specialist Terms
Abbreviation or Specialist 
Term
Explanation
ABC
Activated B-cell like
ADCC
Antibody dependent T cell mediated toxicity
ADL
Activity of daily life
AE
Adverse event
AED
Antiepileptic drug
AESI
Adverse event of special interest
ALL
Acute lymphoblastic leukemia
ALT
Alanine aminotransferase (SGPT)
AST
Aspartate aminotransferase (SGOT)
ATA
Anti-therapeutic antibody
β-hCG
Beta-human chorionic gonadotropin
BCR
B-cell receptor
BMA
Bone marrow aspirate
BMB
Bone marrow biopsy
BNP
Brain natriuretic peptide
BOIN
Bayesian Optimal Interval Design
BTK
Bruton’s tyrosine kinase
CAR
Chimeric antigen receptor
CBC
Complete blood count
CCGs
CRF completion guidelines
CD
Cluster of differentiation
CELMoD
Cereblon E3 ligase modulator
Chemo
Chemotherapy
cHL
Classical Hodgkin lymphoma
CHO
Chinese hamster ovary
CI
Confidence intervals
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Abbreviation or Specialist 
Term
Explanation
CLL
Chronic lymphocytic leukemia
Cmax
Maximum concentration
CMV
Cytomegalovirus
CNS
Central nervous system
COO
Cell of origin
CR
Complete response
CRBN
Cereblon
CRC
Colorectal cancer
CrCl
Creatinine clearance
CRF
Case report form
CRP
C-reactive protein
CRR
Complete response rate
CRS
Cytokine release syndrome
CSF
Cerebrospinal fluid
CT
Computed tomography
CTCAE
Common terminology criteria for adverse events
DHL
Double-hit lymphoma
DL
Dose level
DLBCL
Diffuse large B-cell lymphoma 
DLI
Donor lymphocyte infusion
DLT
Dose-limiting toxicity
DMSO
Dimethyl sulfoxide
DOR
Duration of response
DSMB
Data safety monitoring board
DVT
Deep venous thrombosis
EBV
Epstein-Barr virus
EC
Ethics Committee
ECG
Electrocardiogram
ECHO
Echocardiogram
ECOG
Eastern Cooperative Oncology Group
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Abbreviation or Specialist 
Term
Explanation
EEA
European Economic Area
EEG
Electroencephalogram
EFS
Event-free survival
EGFR
Epidermal growth factor receptor
EMA
European Medicines Agency
EOI
End of infusion
EORTC -QLQ-C30
European Organisation for Research and Treatment of Cancer –
Quality of Life C30 Questionnaire
EOS
End of study
EQ-5D-5L
European Quality of Life-5 Dimensions health state classifier to 5 
Levels
EU
European Union
Fc
Fragment crystallizable
FCBP
Female of child bearing potential
FDA
Food and Drug Administration
FGL-1
Fibrinogen-like protein 1
FL
Follicular lymphoma
flu/ cy
Fludarabine/ cyclophosphamide 
GCB
Germinal center-like
GCP
Good Clinical Practice
GI
Gastrointestinal
GM-CSF
Granulocyte-macrophage colony stimulating factor
GVHD
Graft versus host disease
HBcAB
Hepatitis B core antibody
HBsAb
Hepatitis B surface antibody
HBsAg
Hepatitis B surface antigen
HBV
Hepatitis B virus
HCC
Human cancer cells
HIF
Hypoxia-inducible factor
HIV
Human immunodeficiency virus
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Abbreviation or Specialist 
Term
Explanation
HLA
Human leukocyte antigen
HRQoL
Health-related quality of life
HSCT
Hematopoietic stem cell transplant
IB
Investigator’s brochure
IBC
Institutional biosafety committee
ICF
Informed consent form
ICH
International council for harmonisation
ICU
Intensive care unit
IEC
Independent ethics committee
IFN-γ
Interferon gamma
Ig
Immunoglobulin
IHC
Immunohistochemistry
IKZF1
Ikaros family zinc finger proteins 1
IL
Interleukin
IND
Investigational New Drug
IO
Immuno-oncology
IP
Investigational product
IPI
International Prognostic Index
irAE
Immune-related adverse event
IRB
Institutional review board
IRT
Interactive response technology
ITK
IL-2 inducible T cell kinase
IUD
Intrauterine device
IV
Intravenous
IVIG
Intravenous immunoglobulins
LAG-3
Lymphocyte activation gene 3
LD
Lymphodepleting
LDH
Lactate dehydrogenase
LTFU
Long-term follow-up
LVEF
Left ventricular ejection fraction
mAb
Monoclonal antibody
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Abbreviation or Specialist 
Term
Explanation
MAS
Macrophage activation syndrome
MCL
Mantle cell lymphoma
MedDRA
Medical Dictionary for Regulatory Activities
MHC
Major histocompatibility complex
MM
Multiple myeloma
MRI
Magnetic resonance imaging
MTD
Maximum tolerated dose
MUGA
Multi-gated acquisition scan
NaCl
Sodium chloride
NCI
National Cancer Institute
NHL
Non-Hodgkin lymphoma
NK
Natural killer
NOS
Not otherwise specified
NSAIDs
Nonsteroidal anti-inflammatory drugs
NSCLC
Non-small-cell lung cancer
NT
Neurotoxicity
NYHA
New York Heart Association
ORR
Overall response rate
OS
Overall survival
PBMC
Peripheral blood mononuclear cells
Pd
Pharmacodynamics
PD
Progressive disease
PD1
Programmed cell death 1
PD-L
Programmed cell death ligand 
PE
Pulmonary embolism
PET
Positron emission tomography
PFS
Progression-free survival
PI
Package insert / Prescribing information
PK
Pharmacokinetics
PLCγ
Phosphoinositide phospholipase C-γ
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Abbreviation or Specialist 
Term
Explanation
PMBCL
Primary mediastinal large B-cell lymphoma
PO
Per os (oral)
PPDP
Protocol product deviation plan
PPK
Population pharmacokinetics
PPRMP
Pregnancy prevention and risk management plan
PQC
Product quality complaint
PR
Partial response
PT
Preferred term
q3m
Every 3 months
Q2W
Every 2 weeks
Q4W
Every 4 weeks
QD
Every day
RCC
Renal cell carcinoma
R-CHOP
Rituximab- cyclophosphamide, doxorubicin hydrochloride, vincristine 
sulfate, prednisone
RP2D
Recommended Phase 2 dose and schedule
R/R
Relapsed or refractory
SAE
Serious adverse event
SaO2
Oxygen saturation
SAP
Statistical analysis plan
SCCHN
Squamous cell carcinoma of the head and neck
scFv
Single chain variable fragment
sCRS
Severe cytokine release syndrome
SD
Stable disease
SGOT
Serum glutamic oxaloacetic transaminase 
SGPT
Serum glutamic pyruvic transaminase
SLE
Systemic lupus erythematosus
SLL
Small lymphocytic lymphoma
SOC
System organ class
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Abbreviation or Specialist 
Term
Explanation
SOP
Standard operating procedure
SPD
Sum of product of perpendicular diameters
SRC
Safety review committee 
SUSAR
Suspected unexpected serious adverse reaction
TCR
T cell receptor
TEAE
Treatment-emergent adverse events
TFR
Tumor flare reaction
THL
Triple-hit lymphoma
TIL
Tumor-infiltrating lymphocytes
TLS
Tumor lysis syndrome
TNF
Tumor necrosis factor
TnI
Troponin I
TNM
Tumor, nodes, metastasis
TnT
Troponin T
Treg
Regulatory T cell
ULN
Upper limit of normal
URTI
Upper respiratory tract infection
US/ USA
United States/ United States of America
VTE
Venous thromboembolism
WHO
World Health Organization
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APPENDIX B. PERFORMANCE STATUS BY EASTERN 
COOPERATIVE ONCOLOGY GROUP SCALE
Table 34:
Performance Status by Eastern Cooperative Oncology Group Scale 
Score
Description
0
Fully active, able to carry on all predisease performance without restriction.
1
Restricted in physically strenuous activity but ambulatory and able to carry out work 
of a light or sedentary nature, eg, light housework, office work.
2
Ambulatory and capable of all self-care but unable to carry out any work activities. 
Up and about more than 50% of waking hours.
3
Capable of only limited self-care, confined to bed or chair more than 50% of waking 
hours.
4
Completely disabled. Cannot carry on any self-care. Totally confined to bed or 
chair.
5
Dead.
Oken, 1982.
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APPENDIX H. LOCAL CLINICAL LABORATORY EVALUATIONS
Table 35:
Local Clinical Laboratory Evaluations
Laboratory Panel
Analytes
Chemistry
Glucose, BUN, creatinine, sodium, potassium, chloride, calcium, total protein, 
albumin, total bilirubin, direct bilirubin, alkaline phosphatase, ALT (SGPT), AST 
(SGOT), magnesium, phosphate, bicarbonate, LDH, β2-microglobulin, uric acid, 
triglycerides, troponin-Ta (or troponin-I if unavailable), BNP a
Hematology
CBC with differential
Coagulation
PT, aPTT, INR, fibrinogen, and D-dimer
Urinalysis
Appearance, pH, specific gravity, protein
Glucose, ketones, RBCs, WBCs
Casts, crystals, or other components
Pregnancy
ß-HCG (serum or urinea)
Viral serology
HIV
Hepatitis B (HBsAb, HBsAg, and HBcAb), Hepatitis C (Hep C Ab)
HLA typing
HLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DQB1
Inflammatory markers 
CRP, ferritin
Thyroid function tests
TSH, fT4, fT3
Donor chimerism
% stem cell donor
Disease characterization
Histology, cell of origin, immunochemistry, cytogenetics, molecular sub-typing
Cerebrospinal fluid
RBCs, WBCs with differential, glucose, protein
Immunoglobulins
IgG, IgM, IgA
Abbreviations: ALT (SGPT) = alanine aminotransferase (serum glutamic pyruvic transaminase); aPTT = activated 
partial thromboplastin time; AST (SGOT) = aspartate aminotransferase (serum glutamic oxaloacetic transaminase); 
BNP = brain natriuretic peptide; BUN = blood urea nitrogen; CBC = complete blood count; CRP = C-reactive protein; 
FISH = fluorescence in situ hybridization; fT3= free triiodothyronine; fT4= free thyroxine; HIV= Human 
Immunodeficiency Virus; HLA = human leukocyte antigen; Ig = immunoglobulin; INR = international normalized 
ratio; LDH = lactate dehydrogenase; PT = prothrombin time; RBC = red blood cell; TSH = Thyroid stimulating 
hormone; WBC = white blood cell.
a Only to be performed at the timepoints as specified in the schedule of evaluations. See Section 4.2 for permitted 
substitutions.
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APPENDIX I.
COCKCROFT-GAULT EQUATION FOR CALCULATING 
ESTIMATED CREATININE CLEARANCE
Table 36:
Cockcroft-Gault Equation for Calculating Estimated Creatinine Clearance
Serum creatinine 
units
Gender
Estimated Creatinine Clearance (mL/min)
mg/dL
Male
(140 − subject age [years]) × subject weight (kg)
72 × subject serum creatinine (mg/dL)
Female
(140 − subject age [years]) × subject weight (kg) × 0.85
72 × subject serum creatinine (mg/dL)
μM/dL
Male
(140 − subject age [years]) × subject weight (kg) × 1.23
Subject serum creatinine (μM/dL)
Female
(140 − subject age [years]) × subject weight (kg) × 1.04
Subject serum creatinine (μM/dL)
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APPENDIX V. MEDICATIONS THAT ARE CYP3A4/5 STRONG 
INHIBITORS AND INDUCERS
A comprehensive listing of drugs that are CYP3A4 inhibitors can be accessed online at the 
following address: http://medicine.iupui.edu/clinpharm/ddis/table.aspx.
Table 48:
Medications that are CYP3A4/5 Strong Inhibitors
Drug Class
Generic Name
Human Immunodeficiency Virus (HIV) 
Protease Inhibitor
Atazanavir
Indinavir
Darunavir
Lopinavir
Saquinavir
Nelfinavir
Ritonavir and ritonavir containing coformulations
Antihepaciviral (NS 3/4A) Protease 
Inhibitor 
Boceprevir
Telaprevir
Ombitasvir-paritaprevir- ritonavir
Ombitasvir-paritaprevir- ritonavir plus dasabuvir
CYP450 Inhibitor 
Cobicistat and cobicistat containing coformulations
Azole Antifungal
Itraconazole
Ketoconazole
Posaconazole
Voriconazole
Macrolide antibiotic 
Telithromycin
Clarithromycin
Antiprogestin
Mifepristone
Serotonin Reuptake Inhibitor
Nefazodone
Phosphatidylinositol 3-kinase inhibitor 
Idelalisib
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Table 49:
Medications that are CYP3A4/5 Strong Inducers 
Drug Class
Generic Name
Anticonvulsant 
Carbamazepine
Fosphenytoin
Phenytoin
Phenobarbital
Primidone
Antineoplastic/Antiandrogen 
Enzalutamide
Apalutamide
Antineoplastic agent
Mitotane
Cystic fibrosis agent 
Lumacaftor
Antitubercular 
Rifampin (rifampicin)
Herbal
St. John’s wort
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