Chimeric Antigen Receptor (CAR)-T Cell Therapy for Patients With Hematologic Malignancies
Phase: PHASE2
Conditions: Acute Lymphoblastic Leukemia, Large B-cell Lymphoma
Sponsor: Masonic Cancer Center, University of Minnesota

June 30, 2023 
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Masonic Cancer Center, University of Minnesota 
Blood and Marrow Transplantation Program 
 
 
 
Chimeric Antigen Receptor (CAR)-T Cell Therapy for Patients with B-cell 
Hematologic Malignancies 
MT2017-45 
CPRC #2017LS118 
 
Principal Investigator: 
Veronika Bachanova, MD, PhD 
 
Pediatric Principal Investigator: 
Margaret MacMillan, MD 
 
Collaborators:  
Joseph Maakaron, MD 
Mark Juckett, MD 
 
 
Biostatistician: 
Qing Cao, MS 
 
 
Version Date: 
June 30, 2023  
 
 
 
 
Confidential 
 
 

June 30, 2023 
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Revision History 
Revision # 
Version 
Date 
Detail of Changes 
Consent 
change? 
(Y/N) 
 
6/06/2018 
Original for review 
 
 
07/10/2018 
Updated per CPRC Stipulations: clarified objectives and endpoints and 
statistics for Arms A and C; edited wording and punctuation of eligibility 
criteria for clarity; additional minor edits throughout for consistency 
NA 
 
05/23/2019 
Updated study committee 
Updated Event Reporting Guidelines 
Minor edits to eligibility criteria and  study calendar to align with 
current SOPs 
Section 6.5 clarified patient evaluation may be performed by a 
designated health care provider 
Corrected spelling and grammatical errors 
No 
 
10/07/2020 
Updated Study committee 
Clarified Eligibility Criteria 
Deleted eligibility checklists from protocol – eligibility checklists are 
now kept in Oncore 
Arm C – Added bendamustine back as alternative lymphodepleting 
regimen 
Throughout protocol added Tecartus CAR-T product for MCL (Arm D) 
Removed recommended collection target dose  
Increased window around Yescarta infusion timing 
Updated management of expected AEs to current literature 
Added 9 month clinical care follow up visit 
Yes 
 
11/13/2020 
Minor edits to synopsis, section 3.0 and section 11 per CPRC 
Stipulations 
Yes 
(redated) 
 
02/11/2021  
Schema – removed recommendation for 7 days inpatient monitoring, 
as decision will be made by clinical team 
Section 4 minor edits to inclusion/ exclusion criteria per current 
institutional guidelines; edited typographical errors 
Section 6.1 and 6.2 removed concomitant medications – replaced by 
new appendix VI Tisagenlecleucel washout instructions 
Section 6.4 removed infusion dose guidelines. Dose will be determined 
by will be based on data at the time of infusion. 
Section 8. Updated clinical care activities to current institutional 
guidelines 
Throughout document fixed numbering on headers, appendices, 
corrected typographical errors 
No 
 
05/26/2021 
Updated study committee 
Throughout protocol (synopsis, schema, section 1.1, section 1.2, 
section 2,section 3, section 4.5, section 4.6, section 6, section 9.3 
Yes 

June 30, 2023 
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Revision # 
Version 
Date 
Detail of Changes 
Consent 
change? 
(Y/N) 
section 11) – added arms (eligibility, treatment, and statistics) for 
newly approved CAR-T products Arm E Breyanzi and Arm F Abecma. 
Rationale – these CAR-T products have received FDA approval. This 
protocol was designed to be amended as new CAR-T products are 
approved. 
Synopsis, section 4.2, section 2,  added follicular lymphoma to Arm B, 
rationale -  recent FDA approval for this indication 
Synopsis, section 1.2, Section 11 – clarified that secondary endpoints 
for large cell lymphoma and follicular lymphoma will be evaluated 
separately. Rationale – to keep datapoints separate for different 
indications 
Section 4.0 – minor edits to eligibility criteria for clarity and consistency 
Section 4.8 – updated contraception methods from “highly effective” 
to “effective.” Rationale: guidance from current product package 
inserts 
Section 6 – clarified that the washout guidance for Tisagenlecleucel is 
applicable to all CAR-T products. Rationale – to avoid confusion 
Section 6 – removed prohibited medications table – this was replaced 
by Appendix VI in previous amendment. Rationale – table mistakenly 
not removed in prior amendment 
Section 6.2 – updated leukapheresis instructions to conform to current 
SOPs 
Section 6.4 – updated Peds Kymriah dosing per current manufacturer 
instructions – clarification 
New section 6.8 – added language on follow-up to include guidance for 
patients who are withdrawn from treatment. Rationale – clarification 
per coordinator request 
Section 7.0 – Updated Expected toxicities. Rationale – per new study 
product package inserts 
Section 8 – Updated clinical care activities calendar. Rationale – to 
conform to current BMT program order sets and SOPs 
 
11/03/2021 
Updated study committee 
Updated protocol title to clarify that product is for B-cell malignancies 
Throughout protocol (synopsis, schema, section 1.1, section 1.2, 
section 2,section 3, section 4.5, section 4.6, section 6, section 9.3 
section 11) – added arms (eligibility, treatment, and statistics) for 
newly approved indication Arm G Tecartus for B-Cell ALL. Rationale – 
these CAR-T products have received FDA approval. This protocol was 
designed to be amended as new CAR-T products and indications are 
approved. 
Synopsis, section 1.2, Section 11 – clarified which objectives and 
endpoints are for which indications and products. Rationale – to clarify 
datapoints for different indications 
Synopsis, Section 11 – updated enrollment goal. Rationale – to account 
for new approvals and indications 
Y 
(updated 
study title) 

June 30, 2023 
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2017LS118 
Revision # 
Version 
Date 
Detail of Changes 
Consent 
change? 
(Y/N) 
Section 2 – Updated background to include new research results 
Section 4.0 – minor edits to eligibility criteria for clarity and consistency 
Section 6.5 – Updated product infusion instructions to current standard 
of care 
Section 7.13 – Updated HLH/ MAS risk per new package insert 
Section 8 – Updated clinical care activities calendar. Rationale – to 
conform to current BMT program order sets and SOPs 
Section 9.2 – Specified that CARTOX screening assessments will be 
performed through at least day 14. Rationale – in order to standardize 
procedure and reduce protocol deviations 
 
12/14/2021 
Section 11.4 Edited typographical error per CPRC Stipulation 
No 
 
06/30/2023 
Title page – updated collaborators 
Study synopisis, -  
Section 4.1.1. – removed ‘pediatric’ from diagnosis per admin memo 
3/30/2022,  
Section 4.1.3, section 4.2.3, section 4.4.3,  section 4.4.3, section 4.5.3, 
section 4 6.3 and section 4.7.3 - updated acceptable platelet parameter 
to >30,000 to better reflect current clinical practice 
Section 4.1.5, section 4.2.5, section 4.3.5, section 4.4.5, section 4.5.5, 
section 4.6.5 - removed CNS disease as an exclusion criteria to better 
reflect current clinical practice 
Appendix I, II, V, VI, VII, VIII – removed package insert information per 
admin memo 3/30/2022 
Throughout protocol: updated references to CAR-T product package 
inserts in appendixes to simply refer to package inserts 
Appendix III – renumbered to Appendix I 
Appendix IV – renumbered to Appendix II 
Y (per 
continuing 
review 
updated 
contact 
information 
per most 
recent 
template) 
 
 
 
 

June 30, 2023 
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Table of Contents 
 
Abbreviations ................................................................................................................................................ 9 
Study Synopsis ............................................................................................................................................ 11 
Study Schema .............................................................................................................................................. 13 
1 
Study Objectives ................................................................................................................................. 14 
1.1 
Primary Objective........................................................................................................................ 14 
1.2 
Secondary Objectives .................................................................................................................. 14 
1.3 
Correlative Objective .................................................................................................................. 15 
2 
Background and Rationale .................................................................................................................. 15 
3 
Study Design........................................................................................................................................ 25 
4 
Patient Selection ................................................................................................................................. 26 
4.1 
ARM A (Kymriah) and Arm G (Tecartus) :Refractory/relapsed  B-cell acute lymphoblastic 
leukemia expressing CD19 ...................................................................................................................... 26 
4.1.1 
Age and Disease Status ....................................................................................................... 26 
4.1.2 
Performance Status ............................................................................................................. 26 
4.1.3 
Organ Function .................................................................................................................... 26 
4.1.4 
Other Inclusion Criteria ....................................................................................................... 27 
4.1.5 
Exclusion Criteria ................................................................................................................. 27 
4.2 
ARM B: Yescarta for Relapsed or Refractory diffuse large B cell lymphoma and Follicular 
lymphoma ............................................................................................................................................... 28 
4.2.1 
Age and Disease Status ....................................................................................................... 28 
4.2.2 
Performance Status ............................................................................................................. 28 
4.2.3 
Organ Function .................................................................................................................... 28 
4.2.4 
Other Inclusion Criteria ....................................................................................................... 29 
4.2.5 
Exclusion Criteria ................................................................................................................. 29 
4.3 
ARM C:  Kymriah for relapsed or refractory diffuse large B cell lymphoma Inclusion Criteria ... 30 
4.3.1 
Age and Disease Status ....................................................................................................... 30 
4.3.2 
Performance Status ............................................................................................................. 30 
4.3.3 
Organ Function .................................................................................................................... 30 
4.3.4 
Other Inclusion Criteria ....................................................................................................... 31 
4.3.5 
Exclusion Criteria ................................................................................................................. 31 

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4.4 
ARM D:  Tecartus (Brexucabtagene Autoleucel) for relapsed or refractory mantle cell 
lymphoma ............................................................................................................................................... 32 
4.4.1 
Age and Disease Status ....................................................................................................... 32 
4.4.2 
Performance Status ............................................................................................................. 32 
4.4.3 
Organ Function .................................................................................................................... 32 
4.4.4 
Other Inclusion Criteria ....................................................................................................... 33 
4.4.5 
Exclusion Criteria ................................................................................................................. 33 
4.5 
ARM E:  Breyanzi “lisocabtagene maraleucel” for relapsed or refractory large B-cell lymphoma
 
34 
4.5.1 
Age and Disease Status ....................................................................................................... 34 
4.5.2 
Performance Status ............................................................................................................. 34 
4.5.3 
Organ Function .................................................................................................................... 34 
4.5.4 
Other Inclusion Criteria ....................................................................................................... 35 
4.5.5 
Exclusion Criteria ................................................................................................................. 35 
4.6 
ARM F:  Abecma “Idecabtagene Vicleucel” for relapsed or refractory multiple myeloma ........ 36 
4.6.1 
Age and Disease Status ....................................................................................................... 36 
4.6.2 
Performance Status ECOG 0-1 (2 is permitted if due to effects of myeloma) .................... 36 
4.6.3 
Organ Function .................................................................................................................... 36 
4.6.4 
Other Inclusion Criteria ....................................................................................................... 36 
4.6.5 
Exclusion Criteria ................................................................................................................. 37 
4.7 
Criteria for Females ..................................................................................................................... 37 
4.8 
Methods of contraception .......................................................................................................... 38 
5 
Patient Registration In OnCore ........................................................................................................... 38 
6 
Treatment Plan (as per package insert for FDA approved agents) ..................................................... 39 
6.1 
Prohibited Concomitant Medications and Therapy .................................................................... 39 
6.2 
Leukapheresis ............................................................................................................................. 40 
6.3 
Lymphodepleting chemotherapy ................................................................................................ 41 
6.4 
CAR-T Infusion Eligibility ............................................................................................................. 43 
6.5 
CAR-T Infusion ............................................................................................................................. 44 
6.6 
Supportive Care Guidelines ......................................................................................................... 48 
6.7 
Post CAR-T Adverse Reactions .................................................................................................... 49 
6.8 
Follow Up .................................................................................................................................... 50 

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7 
Management of Selected Expected Toxicities (guided by package insert and not considered 
investigational) ............................................................................................................................................ 50 
7.1 
Acute Infusion reaction ............................................................................................................... 51 
7.2 
Febrile reaction ........................................................................................................................... 51 
7.3 
Cytokine Release Syndrome (CRS) / Macrophage Activation Syndrome (MAS) ......................... 51 
7.4 
Neurologic Toxicities (Immune Effectors Associated Neurotoxicity Syndrome (ICANS) ............ 53 
7.5 
Tumor  lysis syndrome ................................................................................................................ 53 
7.6 
Graft-Versus-Host Disease (GVHD) ............................................................................................. 54 
7.7 
Infection ...................................................................................................................................... 54 
7.8 
B cell depletion ........................................................................................................................... 54 
7.9 
New or secondary malignancies ................................................................................................. 55 
7.10 
Replication-competent lentivirus (RCL) testing .......................................................................... 55 
7.11 
Clonality and insertional oncogenesis ........................................................................................ 56 
7.12 
Liver safety monitoring ............................................................................................................... 56 
7.13 
Hemophagocytic Lymphohistiocytosis (HLH)/ Macrophage activation syndrome (MAS) .......... 56 
7.14 
Effects on Ability to Drive and Use Machines ............................................................................. 57 
7.15 
Side Effects of CAR-T ................................................................................................................... 57 
8 
Clinical Care Activities ......................................................................................................................... 58 
8.1 
Optional Research Samples ........................................................................................................ 62 
9 
Adverse Event Monitoring, Documentation, and Reporting .............................................................. 62 
9.1 
Event Monitoring ........................................................................................................................ 62 
9.2 
Event Documentation ................................................................................................................. 62 
9.3 
Event Reporting .......................................................................................................................... 63 
10 
Study Data Collection and Monitoring ............................................................................................ 64 
10.1 
Data Collection ............................................................................................................................ 64 
10.2 
Data and Safety Monitoring ........................................................................................................ 65 
10.3 
Study Related Monitoring ........................................................................................................... 65 
10.4 
Record Retention ........................................................................................................................ 66 
11 
Statistical Consideration ................................................................................................................. 66 
11.1 
Primary  Endpoint ....................................................................................................................... 67 
11.2 
Secondary Endpoints .................................................................................................................. 67 
11.3 
Analysis of Primary and Secondary Endpoints ............................................................................ 68 

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11.4 
Sample Justification and Accrual ................................................................................................ 68 
11.5 
Early Stopping Rule for Excessive Toxicity during Expansion Component ................................. 69 
12 
Conduct of the Study ...................................................................................................................... 69 
12.1 
Good Clinical Practice ................................................................................................................. 69 
12.2 
Ethical Considerations ................................................................................................................. 69 
12.3 
Informed Consent ....................................................................................................................... 69 
13 
References ...................................................................................................................................... 70 
APPENDIX  - Performance Status Scales ..................................................................................................... 71 
APPENDIX II - Management Of Adverse Events .......................................................................................... 73 
 
PI Contact Information: 
Veronika Bachanova MD, PhD 
Medicine Hematology Office 
MMC 480  
420 Delaware Street SE 
Minneapolis, MN 55455 
phone:  612-625-5469 
email:  bach0173@umn.edu 
Pediatric Principal Investigator: 
Margaret L. MacMillan, MD, MSc, FRCPC 
Professor of Pediatrics 
Blood and Marrow Transplantation & Cellular Therapy 
Program  
University of Minnesota  
MMC 484   
420 Delaware Street SE 
Minneapolis, MN 55455 
612 626-2961 (phone) 
612-626-2815 (fax) 
macmi002@umn.edu (email) 
 
 

June 30, 2023 
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Abbreviations 
AE 
Adverse Event 
ALC 
Absolute Lymphocyte Count 
ALL 
Acute Lymphoblastic Leukemia 
ALT 
Alanine Aminotransferase/Glutamic Pyruvic Transaminase/SGPT  
AST 
Aspartate Aminotransferase/Glutamic Oxaloacetic Transaminase/SGOT  
ATG 
Anti-thymocyte globulin 
B-ALL 
B-cell precursor acute lymphoblastic leukemia 
BM 
Bone Marrow 
BMT 
Bone Marrow Transplantation 
CAR 
Chimeric Antigen Receptor 
CBC 
Complete Blood Count 
CD137 
4-1BB costimulatory molecule 
CNS 
Central Nervous System 
CR 
Complete remission 
CRF 
Case Report/Record Form 
CRi 
Complete remission with incomplete blood count recovery  
CRS 
Cytokine Release Syndrome 
CSF 
Cerebral Spinal Fluid 
CT 
Computed Tomography 
CTCAE 
Common Terminology Criteria for Adverse Events  
CTL019 cells 
CD 19 redirected autologous T cells (also called CART19 T cells)  
DLI 
Donor Lymphocyte Infusion 
DLBCL 
Diffuse Large B Cell Lymphoma 
DOR 
Duration of Remission 
ECG 
Electrocardiogram 
ECHO 
Echocardiogram 
EDC 
Electronic Data Capture 
EFS 
Event Free Survival 
FAB 
Fragment Antigen Binding 
FDA 
Food and Drug Administration 
FISH 
Fluorescent in situ hybridization 
G-CSF 
Granulocyte Colony Stimulating Factor  
GFR 
Glomerular Filtration Rate 
GM-CSF 
Granulocyte Macrophage-Colony Stimulating Factor  
GVHD 
Graft versus Host Disease 
HIV 
Human Immunodeficiency Virus 
INR 
International Normalized Ratio 
IRB 
Institutional Review Board 
IUD 
Intrauterine Device 
LDH 
Lactate Dehydrogenase 

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LFT 
Liver Function Test 
LP 
Lumbar Puncture 
LVEF 
Left Ventricular Ejection Fraction 
MCL 
Mantle Cell Lymphoma 
MRD 
Minimal Residual Disease 
MUGA 
Multiple Uptake Gated Acquisition 
MYC 
A regulator gene located on chromosome 8 that is disregulated via 
translocations in Burkitt's lymphoma/leukemia 
NCCN 
National Comprehensive Cancer Network  
NE 
Norepinephrine Equivalent 
NHL 
non-Hodgkin’s lymphomas 
O2 
Oxygen 
ORR 
Overall Response Rate 
OS 
Overall Survival 
PCR 
Polymerase Chain Reaction 
PHI 
Personal Health Information 
PI 
Principal Investigator 
PML 
Progressive Multifocal Leukoencephalopathy 
PR 
Partial Remission 
aPTT 
Activated Partial Thromboplastin Time  
r/r 
Relapsed or refractory 
RCL 
Replication Competent Lentivirus 
RFS 
Relapse Free Survival 
SAE 
Serious Adverse Event 
scFv 
Single chain Fv fragment of an antibody 
SCID 
Severe Combined Immunodeficiency 
SCT 
Stem Cell Transplantation 
sIg 
Surface Immunoglobulin 
SNP 
Single Nucleic Polymorphisms 
TCR-zeta 
Signaling domain found in the intracellular region of the TCR zeta, 
gamma and epsilon chains  
TKI 
Tyrosine Kinase Inhibitor 
TLS 
Tumor Lysis Syndrome 
ULN 
Upper Limit of Normal 
VSV-G 
Vesicular Stomatitis Virus, Glycoprotein  
 
 

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Study Synopsis 
MT2017-45 Chimeric Antigen Receptor (CAR)-T Cell Therapy for Patients with Hematologic B-
Cell Malignancies 
 
Study 
Design: 
This is a phase II study of FDA-approved CAR-T products for patients with hematologic 
malignancies. The study provides criteria for consistent treatment and management according 
to FDA labelling of CAR-T products and does not contain experimental components.  Patients will 
be assigned to Arms  based on age, diagnosis and treating physician CAR-T product preference. 
Overall remission rate, safety events and other endpoints will be calculated for each Arm 
separately.  
Primary 
Objective: 
The primary objective for Arm A (Kymriah ALL,) is to estimate the complete remission (CR) and 
CRi (without count recovery) rate at day 28 as a composite endpoint  
The primary objective for Arm B (Yescarta) is to estimate the Overall Response Rate (complete 
response + Partial response by Lugano) (ORR) separately for DBLBC and FL. 
The primary objective for Arm C (Kymriah Lymphoma) is to estimate the Overall Response Rate 
(complete response + Partial response by Lugano) (ORR). 
The Primary objective for Arm D (Tecartus for relapsed or refractory mantle cell lymphoma) is 
the Overall Response Rate (complete response + Partial response by Lugano) (ORR).  
The Primary objective for Arm E (Breyanzi) is the Overall Response Rate (complete response + 
Partial response by Lugano) (ORR).  
The Primary objective for Arm F (Abecma) is to estimate the Overall Response Rate (complete 
response + Partial response by IMWG criteria) (ORR).  
The Primary objective for Arm G (Tecartus for relapsed or refractory B-cell precursor acute 
lymphoblastic leukemia (B-ALL)) is to estimate the complete remission (CR) and CRi (without 
count recovery) rate at day 28 as a composite endpoint. 
 
 
Secondary 
Objectives: 
Secondary treatment related objectives for Arm A and Arm G include the following: 
• Evaluate the proportion of patients with MRD-negative CR (or CRi). 
Secondary treatment related objectives for all arms include the following: 
• Evaluate the treatment related mortality (in absence of disease relapse/progression) at day 
28, day 100 and 1 year.   
• Evaluate the Relapse-free Survival (RFS) as evaluated by the time of achievement of 
complete remission to relapse or death. 
• Evaluate the event-free survival (EFS) from the date of the CAR-T infusion through 1 year 
post treatment. 

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• Evaluate the overall Survival (OS) from the date of the CAR-T infusion through the date of 
patient death for any reason. 
• Evaluate the proportion of patients developing grade 3, 4 targeted toxicity of CRS and/or 
neurotoxicity. 
Eligible 
Diseases: 
Arm A: Relapsed or refractory pediatric CD19+ B-cell Acute Lymphoblastic Leukemia; age 0 to ≤ 
25 years at the time of infusion receiving Kymriah “Tisagenlecleucel”  product.  
Arm B: Adults (≥18 years) with relapsed or refractory large B-cell lymphoma and follicular 
lymphoma after two or more lines of systemic chemotherapy receiving Yescarta (“ axicabtagene 
ciloleucel” product. 
Arm C: Adults  (≥18 years) with relapsed or refractory diffuse large B cell lymphoma receiving 
Kymriah “Tisagenlecleucel” product. 
Arm D: Adults  (≥18 years) with relapsed or refractory mantle cell lymphoma receiving Tecartus 
product (“Brexucabtagene Autoleucel”) 
Arm E: Adults  (≥18 years) with relapsed or refractory large B-cell lymphoma receiving Breyanzi 
product (“lisocabtagene maraleucel”) 
Arm F: Adults  (≥18 years) with for relapsed or refractory multiple myeloma receiving Abecma 
product (“Idecabtagene Vicleucel”) 
Arm G: Adults  (≥18 years) with relapsed/refractory B-ALL receiving Tecartus product 
(“Brexucabtagene Autoleucel”) 
Key 
Inclusion 
Criteria 
Adequate organ function as defined in section 4.0; not pregnant; no evidence of uncontrolled 
infection 
Enrollment: 
Approximately 340 patients over 5 years 
 
 
 

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Study Schema 
 
 
 
 
 
 
3-4 weeks prior to planned 
CAR-T Infusion 
CAR-T cells manufacturing  
2-14 days prior to 
planned CAR-T Infusion 
 
Day 0 
CAR-T infusion  
30 days intensive 
monitoring  
 
 
 
 
 
 
 T- Cells collected via Leukapheresis 
 lymphodepleting chemotherapy (suggested regimens in section 6.0) 
CAR-T infusion 
*Need for and the length of inpatient stay may vary. For adults treated with Yescarta, Kymriah, 
Tecartus,  Breyanzi, or Abecma 
Eligibility Glossary 
Arm A Kymriah B-ALL 
Section 4.1 
Arm B Yescarta DLBCL/FL 
Section 4.2 
Arm C Kymriah Lymphoma 
Section 4.3 
Arm D Tecartus for MCL  
Section 4.4 
Arm E Breyanzi DLBCL 
Section 4.5 
Arm F Abecma MM 
Section 4.6 
Arm G: Tecartus  B-ALL 
Section 4.7 
 
 

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1 
Study Objectives 
1.1 
Primary Objective 
The primary objective for Arm A is to estimate the composite rate of complete 
remission (CR) and CRi (without count recovery) rate at day 28. 
The primary objective for Arm B is to estimate the Overall Response Rate 
(complete response + Partial response by Lugano) (ORR) separately for DBLBC and 
FL.  
The primary objective for Arm C is to estimate the Overall Response Rate 
(complete response + Partial response by Lugano) (ORR). 
The primary object for Arm D is  the Overall Response Rate (complete response + 
Partial response by Lugano) (ORR). 
 
The primary object for Arm E is the Overall Response Rate (complete response + 
Partial response by Lugano) (ORR).   
 
The primary object for Arm F is to estimate the Overall Response Rate (complete 
response + Partial response by IMWG criteria) (ORR).   
The Primary objective for Arm G (Tecartus for B-ALL) is to estimate the complete 
remission (CR) and CRi (without count recovery) rate at day 28. 
1.2 
Secondary Objectives 
Secondary treatment related objectives for Arm A include the following: 
• Evaluate the proportion of patients with MRD-negative CR (or CRi). 
 
 
Secondary treatment related objectives for all Arms include the following: 
• Evaluate the treatment related mortality (in absence of disease 
relapse/progression) at day 28, day 100 and 1 year.   
• Evaluate the Relapse-free Survival (RFS) as evaluated by the time of 
achievement of complete remission to relapse or death. 
• Evaluate the event-free survival (EFS) from the date of the CAR-T infusion 
through 1 year post treatment. 
• Evaluate the overall Survival (OS) from the date of the CAR-T infusion 
through the date of patient death for any reason. 

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2017LS118 
• Evaluate the proportion of patients developing grade 3, 4 targeted toxicity 
of CRS and/or neurotoxicity. 
1.3 
Correlative Objective 
• Patients may be co-enrolled to an independent protocol for research blood 
and product collection. 
2 
Background and Rationale 
A recent discovery in immunotherapy includes development of genetically modified 
autologous T cells to express epitopes recognizing various antigens on tumor cells.  
Mechanism of Action of all autologous CAR-T products  
CAR-T19 is a CD19-directed genetically modified autologous T cell immunotherapy which 
involves reprogramming a patient’s own T cells with a transgene encoding a chimeric antigen 
receptor (CAR) to identify and eliminate CD19-expressing malignant and normal cells. The 
CAR is comprised of a murine single-chain antibody fragment which recognizes CD19 and is 
fused to intracellular signaling domains.  The costimulatory domain is CAR-T product specific.  
The CD3 zeta component is critical for initiating T-cell activation and antitumor activity, while 
co-stimulatory enhances the expansion and persistence of CAR-T. Upon binding to CD19-
expressing cells, the CAR transmits a signal to promote T-cell expansion, activation, target cell 
elimination, and persistence of the CAR-T cells.  
KYMRIAH 
KYMRIAH (tisagenlecleucel) is an FDA approved CD19-directed genetically modified 
autologous T cell immunotherapy comprised of autologous T cells that are genetically 
modified using a lentiviral vector to encode an anti-CD19 chimeric antigen receptor (CAR). 
The CAR is comprised of a murine single-chain antibody fragment (scFv) specific for CD19, 
followed by a CD8 hinge and transmembrane region that is fused to the intracellular signaling 
domains for 4-1BB (CD137) and CD3 zeta.  
KYMRIAH is prepared from the patient’s peripheral blood mononuclear cells, which are 
obtained via a standard leukapheresis procedure. The mononuclear cells are enriched for T 
cells, then transduced with the lentiviral vector containing the anti-CD19 CAR transgene, and 
activated with anti-CD3/CD28 antibody coated beads. The transduced T cells are expanded in 
cell culture, washed, and formulated into a suspension, which then is cryopreserved.   
CLINICAL STUDIES  

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Relapsed or Refractory (R/R) B-cell Acute Lymphoblastic Leukemia (ALL)  
In a single-center phase 1-2a study recently reported by Maude et al (2018) the anti-CD19 
chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel (Kymriah) produced high 
rates of complete remission and was associated with serious but mainly reversible toxic 
effects in children and young adults with relapsed or refractory B-cell acute lymphoblastic 
leukemia (ALL).  A phase 2, single-cohort, 25-center, global study of tisagenlecleucel in 
pediatric and young adult patients with CD19+ relapsed or refractory B-cell ALL. The primary 
end point was the overall remission rate (the rate of complete remission or complete 
remission with incomplete hematologic recovery) within 3 months.  For this planned analysis, 
75 patients received an infusion of tisagenlecleucel and could be evaluated for efficacy. The 
overall remission rate within 3 months was 81%, with all patients who had a response to 
treatment found to be negative for minimal residual disease, as assessed by means of flow 
cytometry. The rates of event-free survival and overall survival were 73% (95% confidence 
interval [CI], 60 to 82) and 90% (95% CI, 81 to 95), respectively, at 6 months and 50% (95% CI, 
35 to 64) and 76% (95% CI, 63 to 86) at 12 months. The median duration of remission was not 
reached. Persistence of tisagenlecleucel in the blood was observed for as long as 20 months. 
Grade 3 or 4 adverse events that were suspected to be related to tisagenlecleucel occurred 
in 73% of patients. The cytokine release syndrome occurred in 77% of patients, 48% of whom 
received tocilizumab. Neurologic events occurred in 40% of patients and were managed with 
supportive care, and no cerebral edema was reported.  Kymriah was FDA approved in August 
of 2017 for patients up to age 25 with second or greater relapse or refractory.   
Adult Relapsed or Refractory (r/r) Diffuse Large B-cell Lymphoma (DLBCL)  
The efficacy and safety of KYMRIAH was evaluated in an open-label, multicenter, single-arm 
trial (JULIET; NCT02445248). Eligible patients were ≥ 18 years of age with relapsed or 
refractory DLBCL, who received ≥ 2 lines of chemotherapy, including rituximab and 
anthracycline, or relapsed following autologous hematopoietic stem cell transplantation 
(HSCT). The study excluded patients with active central nervous system malignancy, prior 
allogenic HSCT, an ECOG performance status ≥ 2, a creatinine clearance < 60, alanine 
aminotransferase > 5 times normal, cardiac ejection fraction < 45%, or absolute lymphocyte 
concentration less than 300/μL.  
Following 2 to 11 days after completion of lymphodepleting (LD) chemotherapy consisting of 
either fludarabine (25 mg/m2 i.v. daily for 3 days) and cyclophosphamide (250 mg/m2 i.v. 
daily for 3 days starting with the first dose of fludarabine) or bendamustine (90 mg/m2 i.v. 
daily for 2 days), KYMRIAH was administered as a single intravenous infusion. Bridging 
chemotherapy between leukapheresis and LD chemotherapy was permitted to control 
disease burden. LD chemotherapy could be omitted if the white blood cell count was < 1000 

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cells/μL. The major efficacy outcome measures were objective response rate per Lugano 
criteria [2014] as assessed by an independent review committee and duration of response.  
Of the 160 patients enrolled, 106 patients received tisagenlecleucel, including 92 patients 
who received product manufactured in the U.S. and were followed for at least 3 months or 
discontinued earlier. Eleven out of 160 patients enrolled did not receive tisagenlecleucel due 
to manufacturing failure. Thirty-eight other patients did not receive tisagenlecleucel, 
primarily due to death (n = 16), physician decision (n = 16), and adverse events (n = 3).  
Of the 92 patients receiving KYMRIAH, 90% received physician’s choice of bridging 
chemotherapy in the interval between start of screening and KYMRIAH infusion, among 
whom the median number of bridging chemotherapy regimens was 1 (range: 1 to 5) with 83% 
of patients receiving ≤ 2 regimens. A retrospectively identified sub-group of 68 patients was 
evaluable for the major efficacy outcome measures. Patients included in this sub-group had 
either had no bridging chemotherapy, or had imaging that showed measurable disease after 
completion of bridging chemotherapy, prior to KYMRIAH infusion. Of the 24 patients not 
included, 8 had no evidence of disease at baseline prior to KYMRIAH infusion, 15 did not have 
baseline imaging following bridging chemotherapy, and 1 was excluded because of initial 
misclassification of a neuroendocrine tumor as DLBCL.  
Among the efficacy evaluable population of 68 patients, the baseline characteristics were: 
median age 56 years (range: 22 to 74 years); 71% male; 90% White, 4% Asian, and 3% Black 
or African American; 78% had primary DLBCL not otherwise specified (NOS) and 22% had 
DLBCL following transformation from follicular lymphoma, of whom 17% were identified as 
high grade; and 44% had undergone prior autologous HSCT. The median number of prior 
therapies was 3 (range: 1 to 6), 56% had refractory disease and 44% relapsed after their last 
therapy. Ninety percent of patients received lymphodepleting chemotherapy (66% of 
patients received fludarabine and 24% received bendamustine) and 10% did not receive any 
LD chemotherapy. The median time from leukapheresis and cryopreservation to KYMRIAH 
infusion was 113 days (range: 47 to 196 days). The median dose was 3.5 × 108 CAR-positive 
viable T cells (range: 1.0 to 5.2 × 108 cells). Seventy-three percent of patients received 
KYMRIAH in the inpatient setting.  
Efficacy was established on the basis of complete response (CR) rate and duration of response 
(DOR), as determined by an independent review committee: 
N = 68 
Overall Response Rate (ORR)  (CR+PR).  n (%) (95% CI): n= 34 (50 %) (37.6%, 62.4%) 
Complete Response Rate n (%) (95% CI): n= 22 (32%) (21.5%, 44.8%) 

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Partial Response Rate n (%) (95% CI) : n=12 (18%) (9.5%, 28.8%) 
The median time to first response to KYMRIAH (CR or PR) was 0.9 months (range: 0.7 to 3.3 
months). The median duration of response was not reached. Response durations were longer 
in patients who achieved CR, as compared to patients with a best response of partial response 
(PR). Of the 22 patients who experienced a CR, 9 achieved this status by 1 month, 12 more by 
month 3, and the last by month 6 after KYMRIAH infusion.  
YESCARTA 
YESCARTA is a CD19-directed genetically modified autologous T cell immunotherapy using 
chimeric antigen receptor (CAR) comprising a murine anti-CD19 single chain variable 
fragment (scFv) linked to CD28 and CD3-zeta co-stimulatory domains. The anti-CD19 CAR T 
cells are expanded and infused back into the patient, where they can recognize and eliminate 
CD19-expressing target cells.  
YESCARTA is prepared from the patient’s peripheral blood mononuclear cells, which are 
obtained via a standard leukapheresis procedure. The mononuclear cells are enriched for T 
cells and activated with anti-CD3 antibody in the presence of IL-2, then transduced with the 
replication incompetent retroviral vector containing the anti-CD19 CAR transgene. The 
transduced T cells are expanded in cell culture, washed, formulated into a suspension, and 
cryopreserved.  
CLINICAL STUDIES  
Relapsed or Refractory Large B-Cell Lymphoma  
A single-arm, open-label, multicenter trial ZUMA-1 evaluated the efficacy of a single infusion 
of (axicabtagene ciloleucel) YESCARTA in adult patients with relapsed or refractory aggressive 
B-cell non-Hodgkin lymphoma. Eligible patients had refractory disease to the most recent 
therapy or relapse within 1 year after autologous hematopoietic stem cell transplantation 
(HSCT). The study excluded patients with prior allogeneic HSCT, any history of central nervous 
system lymphoma, ECOG performance status of 2 or greater, absolute lymphocyte count less 
than 100/μL, creatinine clearance less than 60 mL/min, hepatic transaminases more than 2.5 
times the upper limit of normal, cardiac ejection fraction less than 50%, or active serious 
infection. Following lymphodepleting chemotherapy, Yescarta was administered in a single 
intravenous infusion at target dose of 0.5-2 x 106 CAR positive viable T cells/kg. Maximum 
permitted dose was 2x 108.    
Lymphodepleting chemotherapy was administered on day -5,-4 and -3 before YESCARTA. 
Bridging chemotherapy between leukapheresis and lymphodepleting chemotherapy was not 

June 30, 2023 
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permitted. All patients were hospitalized for YESCARTA infusion and for a minimum of 7 days 
afterward.  
Of 111 patients who underwent leukapheresis, 101 received YESCARTA. Of the patients 
treated, the median age was 58 years (range: 23 to 76), 67% were male, and 89% were white. 
Most (76%) had DLBCL, 16% had transformed follicular lymphoma, and 8% had primary 
mediastinal large B-cell lymphoma. The median number of prior therapies was 3 (range: 1 to 
10), 77% of the patients had refractory disease to a second or greater line of therapy, and 
21% had relapsed within 1 year of autologous HSCT.  
One out of 111 patients did not receive the product due to manufacturing failure. Nine other 
patients were not treated, primarily due to progressive disease or serious adverse reactions 
following leukapheresis.   
Efficacy was established on the basis of complete remission (CR) rate and duration of 
response (DOR), as determined by an independent review committee (Table 5 and Table 6). 
The median time to response was 0.9 months (range: 0.8 to 6.2 months). Response durations 
were longer in patients who achieved CR, as compared to patients with a best response of 
partial remission (PR) (Table 6). Of the 52 patients who achieved CR, 14 initially had stable 
disease (7 patients) or PR (7 patients), with a median time to improvement of 2.1 months 
(range: 1.6 to 5.3 months).  
Follicular lymphoma  
On March 5, 2021, the Food and Drug Administration granted accelerated approval to 
axicabtagene ciloleucel (Yescarta, Kite Pharma, Inc.) for adult patients with relapsed or 
refractory follicular lymphoma (FL) after two or more lines of systemic therapy. 
Approval in FL was based on a single-arm, open-label, multicenter trial11 that evaluated 
axicabtagene ciloleucel, a CD19-directed chimeric antigen receptor (CAR) T cell therapy, in 
adult patients with relapsed or refractory FL after two or more lines of systemic therapy, 
including the combination of an anti-CD20 monoclonal antibody and an alkylating agent. 
Following lymphodepleting chemotherapy, axicabtagene ciloleucel was administered as a 
single intravenous infusion. 
The main efficacy measures were objective response rate (ORR) and duration of response 
(DOR) as determined by an independent review committee. Among 81 patients in the primary 
efficacy analysis, the ORR was 91% (95% CI: 83, 96) with a complete remission (CR) rate of 
60% and a median time-to-response of 1 month. The median DOR was not reached, and the 
1-year rate of continued remission was 76.2% (95% CI: 63.9, 84.7). For all leukapheresed 
patients in this trial (n=123), the ORR was 89% (95% CI: 83, 94) with a CR rate of 62%. 

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TECARTUS (Brexucabtagene Autoleucel) 
TECARTUS is a CD19-directed genetically modified autologous T cell immunotherapy 
indicated for the treatment of adult patients with relapsed or refractory mantle cell 
lymphoma (MCL). 
Mechanism of Action 
TECARTUS, a CD19-directed genetically modified autologous T cell immunotherapy, 
containing CD28 and CD3-zeta co-stimulatory domains.   
Clinical Studies 
A single-arm, open-label, multicenter trial (ZUMA-2; NCT02601313) evaluated the efficacy 
and safety of a single infusion of TECARTUS in adult patients with relapsed or refractory 
mantle cell lymphoma (MCL) who had previously received anthracycline- or bendamustine-
containing chemotherapy, an anti-CD20 antibody, and a Bruton tyrosine kinase inhibitor 
(BTKi; ibrutinib or acalabrutinib).8 Eligible patients also had disease progression after their 
last regimen or refractory disease to their most recent therapy. The study excluded patients 
with active or serious infections, prior allogeneic hematopoietic stem cell transplant (HSCT), 
detectable cerebrospinal fluid malignant cells or brain metastases, and any history of central 
nervous system (CNS) lymphoma or CNS disorders.  
Seventy-four patients were leukapheresed, five (7%) of whom did not begin conditioning 
chemotherapy or receive TECARTUS: three (4%) experienced manufacturing failure, one (1%) 
died of progressive disease, and one (1%) withdrew from the study. One patient (1%) received 
lymphodepleting chemotherapy but did not receive TECARTUS due to ongoing active atrial 
fibrillation. Sixty-eight of the patients who were leukapheresed received a single infusion of 
TECARTUS, and 60 of these patients were followed for at least six months after their first 
objective disease response, qualifying them as efficacy-evaluable. Among the 60 efficacy-
evaluable patients, 2 × 106 CAR-positive viable T cells/kg were administered to 54 (90%). The 
remaining six (10%) patients received doses of 1.0, 1.6, 1.8, 1.8, 1.9, and 1.9 × 106 CAR-
positive viable T cells/kg. 
Of the 60 efficacy-evaluable patients, the median age was 65 years (range: 38 to 79 years), 
51 (85%) were male, and 56 (93%) were white. Most (50 patients; 83%) had stage IV disease. 
Twenty patients (33% of 60) had baseline bone marrow examinations performed per 
protocol; of these, ten (50%) were negative, eight (40%) were positive, and two (10%) were 
indeterminate. The median number of prior therapies among all 60 efficacy-evaluable 
patients was three (range: two to five). Twenty-six (43%) of the patients had relapsed after 
or were refractory to autologous HSCT. Twenty-one (35%) had relapsed after their last 

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therapy for MCL, while 36 (60%) were refractory to their last therapy for MCL. Among the 60 
efficacy-evaluable patients, 14 (23%) had blastoid MCL. Following leukapheuresis and prior 
to administration of TECARTUS, 21 (35%) of the 60 patients received bridging therapy. Sixteen 
(27%) were treated with a BTKi, 9 (15%) with a corticosteroid, and 4 (7%) with both a BTKi 
and a corticosteroid.  
Among the 60 efficacy-evaluable patients, the median time from leukapheresis to product 
delivery was 15 days (range: 11 to 28 days), and the median time from leukapheresis to 
product infusion was 27 days (range: 19 to 63 days). The protocol-defined lymphodepleting 
chemotherapy regimen of cyclophosphamide 500 mg/m2 intravenously and fludarabine 30 
mg/m2 intravenously, both given on each of the fifth, fourth, and third days before TECARTUS 
infusion, was administered to 53 (88%) of the 60 efficacy-evaluable patients. The remaining 
seven patients (12%) either received lymphodepletion over four or more days or received 
TECARTUS four or more days after completing lymphodepletion. All treated patients received 
TECARTUS  infusion on Day 0 and were hospitalized until at least Day 7.   
The primary endpoint of objective response rate (ORR) per the Lugano Classification (2014) 
in 60 evaluable patients was 87%, CR rate 62% and PR rate 25%. The median time to response 
was 28 days (range: 24 to 92 days).  DOR for CR patients not reached; range (1.9- 29.2 
months). The median time to response was 28 days (range: 24 to 92 days) with a median 
follow-up time for DOR of 8.6 months. 
TECARTUS for B-ALL 
The efficacy of TECARTUS was evaluated in ZUMA-3 (NCT02614066), an open-label, single-
arm, multicenter trial in adult patients with relapsed or refractory B-cell precursor ALL. 
Eligible patients were adults with primary refractory ALL, first relapse following a remission 
lasting ≤ 12 months, relapsed or refractory ALL after second-line or higher therapy, or 
relapsed or refractory ALL at least 100 days after allogeneic stem cell transplantation (HSCT). 
The study excluded patients with active or serious infections, active graft-vs-host disease or 
taking immunosuppressive medications within 4 weeks prior to enrollment, and any history 
of CNS disorders, including CNS-2 disease with neurologic changes and CNS-3 disease 
irrespective of neurological changes. Treatment consisted of lymphodepleting chemotherapy 
(fludarabine 25 mg/m2 iv daily on Days -4, -3 and -2; cyclophosphamide 900 mg/m2 iv on Day 
-2) followed by a single intravenous infusion of TECARTUS at a target dose of 1 × 106 anti-
CD19 CAR T cells/kg (maximum 1 × 108 cells) on Day 0. All treated patients were hospitalized 
until at least Day 7. 
Seventy-one patients were enrolled and leukapheresed; six of these patients did not receive 
TECARTUS due to manufacturing failure, eight patients were not treated primarily due to 

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adverse events following leukapheresis, two patients underwent leukapheresis and received 
lymphodepleting chemotherapy but were not treated with TECARTUS, and one patient 
treated with TECARTUS was inevaluable for efficacy. Among the remaining 54 efficacy-
evaluable patients, the median time from leukapheresis to product delivery was 16 days 
(range: 11 to 39 days) and the median time from leukapheresis to TECARTUS infusion was 29 
days (range: 20 to 60 days). 
Of the 54 patients who were efficacy evaluable, the median age was 40 years (range: 19 to 
84 years), 61% were male, and 67% were White, 6% were Asian, 2% were Black or African 
American, and 2% were American Indian or Alaska Native. At enrollment, 46% had refractory 
relapse, 26% had primary refractory disease, 20% had untreated second or later relapse, and 
7% had first untreated relapse. Among prior therapies, 43% of patients were previously 
treated with allo-SCT, 46% with blinatumomab, and 22% with inotuzumab. Twenty-six 
percent of patients were Philadelphia chromosome positive (Ph+). Fifty (93%) patients had 
received bridging therapy between leukapheresis and lymphodepleting chemotherapy to 
control disease burden. 
The efficacy of TECARTUS was established on the basis of complete remission (CR) within 3 
months after infusion and the duration of CR (DOCR). Twenty-eight (51.9%) of the 54 
evaluable patients achieved CR, and with a median follow-up for responders of 7.1 months, 
the median DOCR was not reached (Table 8). The median time to CR was 56 days (range: 25 
to 86 days). All efficacy evaluable patients had potential follow-up for ≥ 10 months with a 
median actual follow-up time of 12.3 months (range: 0.3 to 22.1 months). 
Breyanzi “lisocabtagene maraleucel” 
BREYANZI is a CD19-directed genetically modified autologous T cell immunotherapy indicated 
for the treatment of adult patients with relapsed or refractory large B-cell lymphoma after 
two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not 
otherwise specified (including DLBCL arising from indolent lymphoma), high-grade B-cell 
lymphoma, primary mediastinal large B-cell lymphoma, and follicular lymphoma grade 3B.9 
Mechanism of Action 
BREYANZI is a CD19-directed genetically modified autologous cell immunotherapy 
administered as a defined composition to reduce variability in CD8-positive and CD4-positive 
T cell dose. The CAR is comprised of an FMC63 monoclonal antibody derived single chain 
variable fragment (scFv), IgG4 hinge region, CD28 transmembrane domain, 4-1BB (CD137) 
costimulatory domain, and CD3 zeta activation domain. CD3 zeta signaling is critical for 
initiating activation and antitumor activity, while 4-1BB (CD137) signaling enhances the 
expansion T cell and persistence of BREYANZI. 

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Clinical Studies 
The efficacy of BREYANZI was evaluated in an open-label, multicenter, single-arm trial12  in 
adult patients with relapsed or refractory large B-cell non-Hodgkin lymphoma after at least 2 
lines of therapy. The study included patients with ECOG performance status ≤ 2, prior 
autologous and/or allogeneic hematopoietic stem cell transplant (HSCT), and secondary CNS 
lymphoma involvement. The study excluded patients with a creatinine clearance of less than 
30 mL/min, alanine aminotransferase > 5 times the upper limit of normal, or left ventricular 
ejection fraction < 40%. There was no prespecified threshold for blood counts; patients were 
eligible to enroll if they were assessed by the investigator to have adequate bone marrow 
function to receive lymphodepleting chemotherapy. Bridging therapy for disease control was 
permitted between apheresis and the start of lymphodepleting chemotherapy, including 
intrathecal chemotherapy or radiation therapy for treatment of CNS involvement with 
lymphoma. 
Efficacy was based on complete response (CR) rate and duration of response (DOR), as 
determined by an independent review committee (IRC) using 2014 Lugano criteria. The 
median time to first response (CR or partial response [PR]) was 1.0 month (range: 0.7 to 8.9 
months). The median time to first CR was 1.0 month (range 0.8 to 12.5 months). Of the 104 
patients who achieved CR, 23 initially had stable disease (6 patients) or PR (17 patients), with 
a median time to improvement of 2.2 months (range: 0.7 to 11.6 months). 
Response durations were longer in patients who achieved a CR, as compared to patients with 
a best response of PR (Table 6). Of the 104 patients who achieved CR, 68 (65%) had remission 
lasting at least 6 months and 64 (62%) had remission lasting at least 9 months.  
Of the 287 patients who underwent leukapheresis and had radiographically evaluable 
disease, 27 additional patients achieved a respons. The IRC-assessed overall response rate in 
the leukapheresed population (n=287) was 59% (95% CI: 53, 64), with a CR rate of 43% (95% 
CI: 37, 49) and PR rate of 15% (95% CI: 11, 20). These efficacy results include responses that 
may have been contributed solely by bridging therapy, responses after receipt of product 
outside of the intended dose range, and responses to product that did not meet release 
specifications.9 
Abecma “Idecabtagene Vicleucel” 
ABECMA is a B-cell maturation antigen (BCMA)-directed genetically modified autologous T 
cell immunotherapy indicated for the treatment of adult patients with relapsed or refractory 
multiple myeloma after four or more prior lines of therapy, including an immunomodulatory 
agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody.10 

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Mechanism of Action 
ABECMA is a chimeric antigen receptor (CAR)-positive T cell therapy targeting B-cell 
maturation antigen (BCMA), which is expressed on the surface of normal and malignant 
plasma cells. The CAR construct includes an anti-BCMA scFv-targeting domain for antigen 
specificity, a transmembrane domain, a CD3-zeta T cell activation domain, and a 4-1BB 
costimulatory domain.10 
Clinical Studies 
Efficacy of ABECMA was evaluated in KarMMa13, an open-label, single-arm, multicenter study 
in adult patients with relapsed and refractory multiple myeloma who had received at least 3 
prior lines of antimyeloma therapy including an immunomodulatory agent, a proteasome 
inhibitor, and an anti-CD38 monoclonal antibody. The study included patients with ECOG 
performance status of 0 or 1. The study excluded patients with a creatinine clearance of less 
than or equal to 45 mL/minute, alanine aminotransferase >2.5 times upper limit of normal 
and left ventricular ejection fraction <45%. Patients were also excluded if absolute neutrophil 
count <1000 cells/mm3 and platelet count <50,000/mm3. Patients had measurable disease 
by International Myeloma Working Group (IMWG) 2016 criteria at enrollment. Bridging 
therapy with alkylating agents, corticosteroids, immunomodulatory agents, proteasome 
inhibitors, and/or anti-CD38 monoclonal antibodies to which patients were previously 
exposed was permitted for disease control between apheresis and until 14 days before the 
start of lymphodepleting chemotherapy. 
Response durations were longer in patients who achieved a stringent CR as compared to 
patients with a PR or VGPR. Of the 28 patients who achieved a stringent CR, it is estimated 
that 65% (95% CI: 42%, 81%) had a remission lasting at least 12 months. 
The median duration of response for VGPR patients (n=25) was 11.1 months (95% CI: 8.7, 
11.3). 
The median duration of response for PR patients (n=19) was 4.0 months (95% CI: 2.7, 7.2). 
Within the recommended dose of 300 to 460 x 106 CAR-positive T cells, a dose-response 
relationship was observed with higher ORR and sCR rate in patients who received 440 to 460 
x 106 compared to 300 to 340 x 106 CAR-positive T cells. Overall response rate of 79% (95% 
CI: 65%, 90%) and sCR rate of 31% (95% CI: 19%, 46%) was observed with 440 to 460 x 106 
CAR-positive T cells. Overall response rate of 65% (95% CI: 51%, 78%) with sCR rate of 25% 
(95% CI: 14%, 39%) was observed in 300 to 340 x 106 CAR-positive T cells. 

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One hundred and thirty-five patients underwent leukapheresis. Fifteen out of the 23 patients 
who received treatment outside of the recommended dose range of 300 to 460 x 106 CAR-
positive T cells experienced a response in addition to the responses noted in Table 6. The IRC 
assessed overall response in the leukapheresis population (n=135) was 64% (95% CI: 56%, 
72%) with stringent CR rate of 24% (95% CI: 17%, 32%), VGPR rate of 21% (95% CI: 14%, 29%) 
and PR rate of 20% (95% CI: 14%, 28%). 
3 
Study Design 
This is a phase II study of FDA-approved CAR-T products for patients with hematologic 
malignancies.  The study provides criteria for consistent treatment and management 
according to FDA labelling of CAR-T products and does not contain experimental components. 
There are no experimental components related to eligibility, treatment and management of 
CAR-T therapies.  
 
This study will have multiple treatment arms based on disease and choice of CAR-T product. 
For the patients who are eligible for more than one Arm, Arm choice additionally may depend 
upon treating physician preference, insurance company prior authorization, or drug 
availability:   
• ARM A:  Relapsed or refractory pediatric CD19+ B-cell Acute Lymphoblastic Leukemia 
treated with Kymriah 
• ARM B:  Relapsed or refractory large B-cell lymphoma or Follicular lymphoma  treated 
with Yescarta 
• Arm C: Adult patients with relapsed and refractory diffuse large B cell lymphoma 
treated with Kymriah. 
• Arm D: Adults  (≥18 years) with relapsed or refractory mantle cell lymphoma receiving 
Tecartus product (Brexucabtagene Autoleucel) 
• Arm E: Adults  (≥18 years) with relapsed or refractory large B-cell lymphoma receiving 
Breyanzi product (“lisocabtagene maraleucel”) 
• Arm F: Adults  (≥18 years) with for relapsed or refractory multiple myeloma receiving 
Abecma product (“Idecabtagene Vicleucel”) 
• Arm G: Adults  (≥18 years) with B-ALL receiving Tecartus product (Brexucabtagene 
Autoleucel) 
 
Lymphodepleting chemotherapy options are summarized in “Lymphodepleting 
chemotherapy guidelines” to provide the treating physician with individual patient 
flexibility.  

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4 
Patient Selection 
Study entry is open to persons of any age regardless of gender, race or ethnic background.  
While there will be every effort to seek out and include females and minority patients, 
the patient population is expected to be no different than that of similar studies at the 
University of Minnesota. 
4.1 
ARM A (Kymriah) and Arm G (Tecartus) :Refractory/relapsed  B-cell 
acute lymphoblastic leukemia expressing CD19 
4.1.1 Age and Disease Status 
o Must be age 0- ≤ 25 years (for Arm A Kymriah) or >18 years (Arm G 
Tecartus) 
o Disease status: Relapsed and refractory B-cell ALL defined by one of 
these: 
• Primary induction failure with no complete remission after ≥2 
cycles of induction chemotherapy, or 
• Patients with persistent minimal residual disease (MRD >0.01% 
by flow cytometry or persistent by cytogenetic or molecular 
assays)  after ≥2 cycles of consolidation chemotherapy, or 
• First relapse following remission lasting <12 months 
• Patients in 2nd or greater relapse of B-ALL or 
• Down Syndrome or other congenital diseases assuming that 
they fit the criteria for second or greater relapse or refractory 
leukemia, or 
• Patients with Ph+ ALL who have failed or are intolerant to two 
lines of TKI assuming they fit the criteria for second or greater 
relapse or are considered refractory.  
• Relapsed or refractory ALL after allogeneic stem cell 
transplantation and off immunosupression 
4.1.2 Performance Status  
o Arm A: Karnofsky (age ≥16 years) or Lansky (age < 16 years) 
performance status ≥ 50% at screening; Arm G: ECOG 0, 1 or 2 
4.1.3 Organ Function  
o Renal function defined as: 
• A serum creatinine of ≤1.5 x ULN OR 
• eGFR ≥ 40 mL/min/1.73 m2 
o Liver function defined as: 

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• ALT ≤ 5 times the ULN for age (unless due to disease) 
• Bilirubin ≤ 2.0 mg/dl with the exception of patients with Gilbert 
syndrome; may be included if their total bilirubin is ≤ 3.0 x ULN 
and direct bilirubin ≤ 1.5 x ULN 
o Must have a minimum level of pulmonary reserve defined as ≤ Grade 
1 dyspnea and pulse oxygenation SpO2 > 88% on room air 
o Hemodynamically 
stable 
and 
LVEF 
≥ 
40% 
confirmed 
by 
echocardiogram or MUGA 
4.1.4 Other Inclusion Criteria 
o Life expectancy ≥12 weeks 
o Women of child bearing potential and sexually active males with 
partners of child bearing potential must agree to use adequate birth 
control for the duration of treatment. See section 4.7 for definitions of 
child bearing potential and section 4.8 for definitions of adequate birth 
control. 
o Written voluntary consent (adults) or parental/guardian consent 
(minors or adults with diminished capacity) prior to the performance 
of any research related tests or procedures. 
o See sections 4.7 and 4.8  for additional criteria involving pregnancy and 
contraception. 
4.1.5 Exclusion Criteria 
o Pregnant or breastfeeding - Females of childbearing potential must 
have a blood test or urine study within 14 days prior to registration to 
rule out pregnancy. 
o Patients with Burkitt’s lymphoma/leukemia (i.e. patients with mature 
B-cell ALL, leukemia with B-cell [sIg positive and kappa or lambda 
restricted positivity] ALL, with FAB L3 morphology and /or a MYC 
translocation) 
o Presence of Grade 2 to 4 acute or extensive chronic graft-versus-host 
disease (GVHD). All GVHD medication must be stopped 1 week prior to 
apheresis. 
o Uncontrolled active hepatitis B or hepatitis C 
o Active HIV infection 
o Uncontrolled acute life threatening bacterial, viral or fungal infection 
(e.g. blood culture positive ≤ 72 hours prior to infusion) 
o Unstable angina and/or myocardial infarction within 1 month prior to 
CAR-T infusion  

June 30, 2023 
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o Investigational medicinal product within the last 7 days prior to 
apheresis or CAR-T infusion 
o Intolerance to the excipients of the CAR-T cell product 
o Patient has taken one of the prohibited concomitant medications 
within the timeframe outlined in package insert. 
4.2 
ARM B: Yescarta for Relapsed or Refractory diffuse large B cell 
lymphoma and Follicular lymphoma 
4.2.1 Age and Disease Status 
o Adult patients (age ≥ 18 years)  
o One of the following histologies and expression of CD19 by tumor cells: 
• 
diffuse large B-cell lymphoma (DLBCL) not otherwise specified, 
or 
• 
primary mediastinal large B-cell lymphoma, or 
• 
high grade B-cell lymphoma, or 
• 
DLBCL arising from follicular lymphoma 
• 
Follicular lymphoma any grade  
 
o Disease status: 
• 
Chemotherapy 
refractory 
disease 
after 
≥2 
lines 
of 
chemotherapy, or 
• 
Relapsed with no remission after ≥1 lines of salvage 
chemotherapy, or   
• 
Relapsed following autologous HCT (and failed at least 2 prior 
lines of therapy including high dose chemotherapy). If salvage 
therapy is given post autoHCT, the subject must have no 
complete response, or relapse after the last line of therapy  
 
o Measurable disease at time of apheresis : 
• 
Nodal lesions or extranodal lesion    
4.2.2 Performance Status  
o ECOG performance status 0-1 (ECOG 2 permissible for FL) 
4.2.3 Organ Function  
o Renal function defined as: 

June 30, 2023 
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• 
A serum creatinine of ≤1.5 x ULN OR 
• 
eGFR ≥ 40 mL/min/1.73 m2 
o Liver function defined as: 
• 
ALT ≤ 5 times the ULN for age (unless due to disease) 
• 
Bilirubin ≤ 2.0 mg/dl with the exception of patients with Gilbert 
syndrome; may be included if their total bilirubin is ≤ 3.0 x ULN 
and direct bilirubin ≤ 1.5 x ULN 
o Must have a minimum level of pulmonary reserve defined as ≤ Grade 
1 dyspnea and pulse oxygenation SpO2 > 91% on room air 
o Hemodynamically 
stable 
and 
LVEF 
≥ 
45% 
confirmed 
by 
echocardiogram or MUGA 
o Adequate bone marrow reserve (unless marrow infiltrated by disease) 
defined as : 
• 
Absolute neutrophil count (ANC) > 1,000/mm3 (only for NHL) 
• 
Platelets ≥ 30,000/mm3 (transfusion support can be provided) 
• 
Hemoglobin >8.0 mg/dl (transfusion support can be provided) 
4.2.4 Other Inclusion Criteria 
o Life expectancy ≥12 weeks 
o Women of child bearing potential and sexually active males with 
partners of child bearing potential must agree to use adequate birth 
control for the duration of treatment. See section 4.7 for definitions of 
child bearing potential and section 4.8 for definitions of adequate birth 
control. 
o Written voluntary consent (adults) or parental/guardian consent 
(minors or adults with diminished capacity) prior to the performance 
of any research related tests or procedures. 
o See sections 4.7 and 4.8  for additional criteria involving pregnancy and 
contraception. 
4.2.5 Exclusion Criteria 
o Pregnant or breastfeeding - Females of childbearing potential must 
have a blood test or urine study within 14 days prior to registration to 
rule out pregnancy. 
o Presence of Grade 2 to 4 acute or extensive chronic graft-versus-host 
disease (GVHD). All GVHD medication must be stopped 1 week prior to 
apheresis. 

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o Uncontrolled active hepatitis B or hepatitis C 
o Active HIV infection (controlled HIV is permissible)  
o Uncontrolled acute life threatening bacterial, viral or fungal infection 
(e.g. blood culture positive ≤ 72 hours prior to infusion) 
o Unstable angina and/or myocardial infarction within 1 month prior to 
CAR-T infusion  
o Investigational medicinal product within the last 7 days prior to 
apheresis or CAR-T infusion 
o Intolerance to the excipients of the CAR-T cell product 
o Any immunosuppressive medication must be stopped ≥ 2 weeks prior 
to apheresis (steroids must be stopped >72 hours prior to apheresis).  
o Patient has taken one of the prohibited concomitant medications 
within the timeframe outlined in the package insert. 
4.3 
ARM C:  Kymriah for relapsed or refractory diffuse large B cell 
lymphoma Inclusion Criteria 
4.3.1 Age and Disease Status 
• Adult patients (age ≥ 18 years)  
• with relapsed or refractory (r/r) large B-cell lymphoma, including 
o diffuse large B-cell lymphoma (DLBCL) not otherwise specified, 
o high grade B-cell lymphoma  
o DLBCL arising from follicular lymphoma.   
• Disease status:  
o after two or more lines of systemic therapy or  
o relapse after autologous HCT  
4.3.2 Performance Status  
o ECOG performance status 0-2  
4.3.3 Organ Function  
o Renal function defined as: 
• 
A serum creatinine of ≤1.5 x ULN OR 
• 
eGFR ≥ 30 mL/min/1.73 m2 
o Liver function defined as: 
• 
ALT ≤ 5 times the ULN for age (unless due to disease) 

June 30, 2023 
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• 
Bilirubin ≤ 2.0 mg/dl with the exception of patients with Gilbert 
syndrome; may be included if their total bilirubin is ≤ 3.0 x ULN 
and direct bilirubin ≤ 1.5 x ULN 
o Must have a minimum level of pulmonary reserve defined as ≤ Grade 
1 dyspnea and pulse oxygenation SpO2 > 91% on room air 
o Hemodynamically 
stable 
and 
LVEF 
≥ 
40% 
confirmed 
by 
echocardiogram or MUGA 
o Adequate bone marrow reserve (unless marrow infiltrated by disease) 
defined as : 
• 
Absolute neutrophil count (ANC) > 1,000/mm3 (only for NHL) 
• 
Platelets ≥ 30,000/mm3 (transfusion support can be provided) 
• 
Hemoglobin >8.0 mg/dl (transfusion support can be provided) 
4.3.4 Other Inclusion Criteria 
o Life expectancy ≥12 weeks 
o Women of child bearing potential and sexually active males with 
partners of child bearing potential must agree to use adequate birth 
control for the duration of treatment. See section 4.7 for definitions of 
child bearing potential and section 4.8 for definitions of adequate birth 
control. 
o Written voluntary consent (adults) or parental/guardian consent 
(minors or adults with diminished capacity) prior to the performance 
of any research related tests or procedures. 
o See sections 4.7 and 4.8  for additional criteria involving pregnancy and 
contraception. 
4.3.5 Exclusion Criteria 
o Pregnant or breastfeeding - Females of childbearing potential must 
have a blood test or urine study within 14 days prior to registration to 
rule out pregnancy. 
o Presence of Grade 2 to 4 acute or extensive chronic graft-versus-host 
disease (GVHD). All GVHD medication must be stopped 2 weeks prior 
to apheresis. 
o Uncontrolled active hepatitis B or hepatitis C 
o Active HIV infection  
o Uncontrolled acute life threatening bacterial, viral or fungal infection 
(e.g. blood culture positive ≤ 72 hours prior to infusion) 

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o Unstable angina and/or myocardial infarction within 1 month prior to 
CAR-T infusion  
o Investigational medicinal product within the last 7 days prior to 
apheresis or CAR-T infusion 
o Intolerance to the excipients of the CAR-T cell product 
o Any immunosuppressive medication must be stopped ≥ 2 weeks prior 
to apheresis (steroids must be stopped >72 hours prior to apheresis).  
o Patient has taken one of the prohibited concomitant medications 
within the timeframe outlined in package insert 
4.4 
ARM D:  Tecartus (Brexucabtagene Autoleucel) for relapsed or 
refractory mantle cell lymphoma  
4.4.1 Age and Disease Status 
• Adult patients (age ≥ 18 years)  
• with relapsed or refractory (r/r) mantle cell lymphoma, including 
o prior 
1st 
line 
therapy 
(containing 
anthracycline 
or 
Bendamustine  or cytarabine or other) 
o prior Rituximab or other CD20 directed antibody (or inability to 
treat with CD20 MoAb)   
o not a candidate or relapse after autologous HCT  
o active disease at enrollment  
4.4.2  Performance Status  
o ECOG performance status 0-1  
4.4.3 Organ Function  
o Renal function defined as: 
• 
A serum creatinine of ≤1.5 x ULN OR 
• 
eGFR ≥ 50 mL/min/1.73 m2 
o Liver function defined as: 
• 
ALT ≤ 5 times the ULN for age (unless due to disease) 
• 
Bilirubin ≤ 2.0 mg/dl with the exception of patients with Gilbert 
syndrome; may be included if their total bilirubin is ≤ 3.0 x ULN 
and direct bilirubin ≤ 1.5 x ULN 
o Must have a minimum level of pulmonary reserve defined as ≤ Grade 
1 dyspnea and pulse oxygenation SpO2 > 91% on room air 

June 30, 2023 
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o Hemodynamically 
stable 
and 
LVEF 
≥ 
45% 
confirmed 
by 
echocardiogram or MUGA 
o Adequate bone marrow reserve (unless marrow infiltrated by disease) 
defined as : 
• 
Absolute neutrophil count (ANC) > 1,000/mm3 (only for NHL) 
• 
Platelets ≥ 30,000/mm3 (transfusion support can be provided) 
• 
Hemoglobin >8.0 mg/dl (transfusion support can be provided) 
4.4.4 Other Inclusion Criteria 
o Life expectancy ≥12 weeks 
o Women of child bearing potential and sexually active males with 
partners of child bearing potential must agree to use adequate birth 
control for the duration of treatment. See section 4.7 for definitions of 
child bearing potential and section 4.8 for definitions of adequate birth 
control. 
o Written voluntary consent (adults) or parental/guardian consent 
(minors or adults with diminished capacity) prior to the performance 
of any research related tests or procedures. 
o See sections 4.7 and 4.8  for additional criteria involving pregnancy and 
contraception. 
4.4.5 Exclusion Criteria 
o Pregnant or breastfeeding - Females of childbearing potential must 
have a blood test or urine study within 14 days prior to registration to 
rule out pregnancy. 
o Presence of Grade 2 to 4 acute or extensive chronic graft-versus-host 
disease (GVHD). All GVHD medication must be stopped 2 weeks prior 
to apheresis. 
o Uncontrolled active hepatitis B or hepatitis C 
o Active HIV infection  
o Uncontrolled acute life threatening bacterial, viral or fungal infection 
(e.g. blood culture positive ≤ 72 hours prior to infusion) 
o Unstable angina and/or myocardial infarction within 1 month prior to 
CAR-T infusion  
o Investigational medicinal product within the last 7 days prior to 
apheresis or CAR-T infusion 
o Intolerance to the excipients of the CAR-T cell product 

June 30, 2023 
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o Any immunosuppressive medication must be stopped ≥ 2 weeks prior 
to apheresis (steroids must be stopped >72 hours prior to apheresis).  
o Patient has taken one of the prohibited concomitant medications 
within the timeframe outlined in the package insert 
4.5 
ARM E:  Breyanzi “lisocabtagene maraleucel” for relapsed or refractory 
large B-cell lymphoma  
4.5.1 Age and Disease Status 
• Adult patients (age ≥ 18 years)  
• with relapsed or refractory disease after two or more lines of systemic 
therapy, including 
o diffuse large B-cell lymphoma (DLBCL) not otherwise specified 
(including DLBCL arising from indolent lymphoma),  
o high-grade B-cell lymphoma,  
o primary mediastinal large B-cell lymphoma, 
o follicular lymphoma grade 3B  
4.5.2  Performance Status  
o ECOG performance status 0-2  
4.5.3 Organ Function  
• Renal function defined as: 
o A serum creatinine of ≤1.5 x ULN OR 
o eGFR ≥ 30 mL/min/1.73 m2 
o Liver function defined as: 
• 
ALT ≤ 5 times the ULN for age (unless due to disease) 
o 
 
• 
Bilirubin ≤ 2.0 mg/dl with the exception of patients with Gilbert 
syndrome; may be included if their total bilirubin is ≤ 3.0 x ULN 
and direct bilirubin ≤ 1.5 x ULN 
o Must have a minimum level of pulmonary reserve defined as ≤ Grade 
1 dyspnea and pulse oxygenation SpO2 > 91% on room air 
o Hemodynamically 
stable 
and 
LVEF 
≥ 
40% 
confirmed 
by 
echocardiogram or MUGA 
o Adequate bone marrow reserve (unless marrow infiltrated by disease) 
defined as : 
• 
Absolute neutrophil count (ANC) > 1,000/mm3 (only for NHL) 

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• 
Platelets ≥ 30,000/mm3 (transfusion support can be provided) 
• 
Hemoglobin >8.0 mg/dl (transfusion support can be provided) 
4.5.4 Other Inclusion Criteria 
o Life expectancy ≥12 weeks 
o Women of child bearing potential and sexually active males with 
partners of child bearing potential must agree to use adequate birth 
control for the duration of treatment. See section 4.7 for definitions of 
child bearing potential and section 4.8 for definitions of adequate birth 
control. 
o Written voluntary consent (adults) or parental/guardian consent 
(minors or adults with diminished capacity) prior to the performance 
of any research related tests or procedures. 
o See sections 4.7 and 4.8  for additional criteria involving pregnancy and 
contraception. 
4.5.5 Exclusion Criteria 
o Pregnant or breastfeeding - Females of childbearing potential must 
have a blood test or urine study within 14 days prior to registration to 
rule out pregnancy. 
o Presence of Grade 2 to 4 acute or extensive chronic graft-versus-host 
disease (GVHD). All GVHD medication must be stopped 2 weeks prior 
to apheresis. 
o Uncontrolled active hepatitis B or hepatitis C 
o Active HIV infection  
o Uncontrolled acute life threatening bacterial, viral or fungal infection 
(e.g. blood culture positive ≤ 72 hours prior to infusion) 
o Unstable angina and/or myocardial infarction within 1 month prior to 
CAR-T infusion  
o Investigational medicinal product within the last 7 days prior to 
apheresis or CAR-T infusion 
o Intolerance to the excipients of the CAR-T cell product 
o Any immunosuppressive medication must be stopped ≥ 2 weeks prior 
to apheresis (steroids must be stopped >72 hours prior to apheresis).  
o Patient has taken one of the prohibited concomitant medications 
within the timeframe outlined in the package insert 

June 30, 2023 
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4.6 
ARM F:  Abecma “Idecabtagene Vicleucel” for relapsed or refractory 
multiple myeloma  
4.6.1 Age and Disease Status 
• Adult patients (age ≥ 18 years)  
o Relapsed (progression after prior partial or complete remission) 
or refractory multiple myeloma  
o Evidence of active disease (medullary or extramedullary) 
o Prior 
therapy 
(Failure 
or 
intolerance 
to) 
with 
an 
immunomodulatory agent, a proteasome inhibitor, and an anti-
CD38 monoclonal antibody     
4.6.2  Performance Status ECOG 0-1 (2 is permitted if due to effects of 
myeloma) 
4.6.3 Organ Function  
o Renal function defined as: 
• 
A serum creatinine of ≤2 x ULN or 
• 
eGFR ≥ 50 mL/min/1.73 m2 
o Liver Function as defined as : 
• 
ALT ≤ 5 times the ULN for age (unless due to disease) 
• 
Bilirubin ≤ 2.0 mg/dl with the exception of patients with Gilbert 
syndrome; may be included if their total bilirubin is ≤ 3.0 x ULN 
and direct bilirubin ≤ 1.5 x ULN 
o Must have a minimum level of pulmonary reserve defined as ≤ Grade 
1 dyspnea and pulse oxygenation SpO2 > 91% on room air 
o Hemodynamically 
stable 
and 
LVEF 
≥ 
45% 
confirmed 
by 
echocardiogram or MUGA 
o Adequate bone marrow reserve (unless marrow infiltrated by disease) 
defined as : 
• 
Platelets ≥ 30,000/mm3 (transfusion support can be provided) 
• 
Hemoglobin >8.0 mg/dl (transfusion support can be provided) 
4.6.4 Other Inclusion Criteria 
o Life expectancy ≥12 weeks 
o Women of child bearing potential and sexually active males with 
partners of child bearing potential must agree to use adequate birth 

June 30, 2023 
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2017LS118 
control for the duration of treatment. See section 4.7 for definitions of 
child bearing potential and section 4.8 for definitions of adequate birth 
control. 
o Written voluntary consent (adults) or parental/guardian consent 
(minors or adults with diminished capacity) prior to the performance 
of any research related tests or procedures. 
o See sections 4.7 and 4.8  for additional criteria involving pregnancy and 
contraception. 
4.6.5 Exclusion Criteria 
o Pregnant or breastfeeding - Females of childbearing potential must 
have a blood test or urine study within 14 days prior to registration to 
rule out pregnancy. 
o Presence of Grade 2 to 4 acute or extensive chronic graft-versus-host 
disease (GVHD). All GVHD medication must be stopped 2 weeks prior 
to apheresis. 
o Uncontrolled active hepatitis B or hepatitis C 
o Active HIV infection  
o Uncontrolled acute life threatening bacterial, viral or fungal infection 
(e.g. blood culture positive ≤ 72 hours prior to infusion) 
o Unstable angina and/or myocardial infarction within 1 month prior to 
CAR-T infusion  
o Investigational medicinal product within the last 7 days prior to 
apheresis or CAR-T infusion 
o Intolerance to the excipients of the CAR-T cell product 
o Any immunosuppressive medication must be stopped ≥ 2 weeks prior 
to apheresis (steroids must be stopped >72 hours prior to apheresis).  
o Patient has taken one of the prohibited concomitant medications 
within the timeframe outlined in package insert 
4.7 
Criteria for Females 
Women who are not of reproductive potential (defined as either <11 years of age, 
Tanner Stage 1, post-menopausal for at least 24 consecutive months (i.e. have had 
no menses) or have undergone hysterectomy, bilateral salpingectomy, and/or 
bilateral oophorectomy) are eligible without requiring the use of contraception. 
Women who are not yet of reproductive potential are to agree to use acceptable 
forms of contraception when they reach reproductive potential if within 1 year of 
CAR-T 
infusion. 
Acceptable 
documentation 
includes 
written 
or 
oral 

June 30, 2023 
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2017LS118 
documentation communicated by clinician or clinician’s staff of one of the 
following: 
o Demographics show age <11 
o Physical examination indicates Tanner Stage 1 
o Physician report/letter 
o Operative report or other source documentation in the patient 
record 
o Discharge summary 
o Follicle stimulating hormone measurement elevated into the 
menopausal range 
4.8 
Methods of contraception 
Women of child-bearing potential (defined as all women physiologically capable 
of becoming pregnant) and all male participants, must agree to use effective 
methods of contraception for the duration of treatment and a period of 1 year 
after the CAR-T infusion. According to the World Health Organization and the 
United States Center for Disease Control and Prevention, the most effective forms 
of birth control include complete abstinence, surgical sterilization (both male and 
female), intrauterine devices (IUDs), and the contraceptive implant.  The next 
most effective forms of birth control include injectables, oral contraceptive pills, 
the contraceptive ring, or the contraceptive patch.  Acceptable, but least effective, 
methods of birth control include male condoms (with or without spermicide) and 
female condoms.  
5 
Patient Registration In OnCore 
Registration will occur after the patient/parent/guardian has signed the subject consent 
and eligibility is confirmed.  To be eligible for registration to this study, the patient must 
meet each criteria listed on the eligibility checklist based on the eligibility assessment 
documented in the patient’s medical record.  A copy of the eligibility checklist is under 
attachments within the study in OnCore. 
Patients will be registered in OnCore by the Masonic Cancer Center’s Clinical Data 
Associates (CDA’s).  Each patient will be assigned to a study treatment arm based on 
diagnosis. 

June 30, 2023 
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6 
Treatment Plan (as per package insert for FDA approved agents) 
In order to provide optimal patient care and to account for individual medical conditions, 
investigator discretion may be used in the prescribing of all supportive care drug therapy 
(i.e. acetaminophen, diphenhydramine, antimicrobials, etc.). 
All treatment will be given per current institutional guidelines with individual patient 
modifications as clinically indicated.  All drugs are commercially available.   
 
Details of the treatment plan are found in the following sections: 
 
 
 
6.1 
Prohibited Concomitant Medications and Therapy 
The following guidelines should be followed during the study: 
● Granulocyte macrophage-colony stimulating factor (GM-CSF) should be 
avoided due to the potential to worsen CRS symptoms.  
● Granulocyte colony stimulating factor (G-CSF) should not be given within 72 
hours of CAR-T infusion and long acting G-CSF should not be given within 10 
days of CAR-T infusion. 
● Steroids or other immunosuppressant drugs should NOT be used as pre-
medication for CAR-T therapy or following CAR-T infusion, except as required 
for physiological glucocorticoid replacement therapy,   
● Use of steroids with blood product administration should be eliminated just 
prior to and following CAR-T if possible or at least minimized. 
 
The following medications are not allowed: please refer to the most recent Washout 
Guidance Prior to Tisagenlecleucel in package insert.  
NOTE: the washout guidance for Tisagenlecleucel is applicable to all CAR-T products, 
with exceptions for myeloma noted in section 6.2. Ibrutinib and radiation therapy is 
permitted during apheresis for all Arms. 
 
 
Prohibited Concomitant Medications and Therapy 
section 6.1 
Leukapheresis 
section 6.2 
Lymphodepleting chemotherapy 
section 6.3 
CAR-T Infusion Eligibility 
section 6.4 
CAR-T Infusion 
section 6.5 
Supportive Care Guidelines 
section 6.6 
Post CAR-T Reactions 
section 6.7 

June 30, 2023 
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6.2 
Leukapheresis 
Patients will undergo leukapheresis to collect autologous T-cells, which will be used to 
manufacture the CAR-T autologous cellular immunotherapy product. Please refer to the most 
recent Washout Guidance Prior to CAR-T therapy in package insert.  
 
• Confirm Leukapheresis Eligibility (Eligibility Checklist kept in Oncore ) 
● Patient has to be eligible for CAR-T therapy per FDA label  (Eligibility Checklists for 
each arm kept in Oncore) 
● Collect CBC (CDC/diff and T cell subset (LAB 3245) at least 24 hours prior apheresis) 
● Review absolute lymphocyte count (ALC) (preferred to be >100 but not required) 
● Use standard Apheresis order set  
● Collect daily CBC/differential on day of collection  
• Add T cell subsets (LAB3245) for product to Apheresis Order Set  
● Suggested target yield (not routinely calculated in real time) : CD3+ lymphocyte 
count >/= 1.0 x 109  cells AND target total nucleated cell dose (TNC) count  >/= 
2.0 x 109  
● One collection is typically planned.  
● Leukapheresis material will be then shipped to the CAR-T manufacturer by MCT 
facility using SOP.  
● Recommendations prior to apheresis: 
▪ 
IMiDs -lenalidomide/pomalidomide and Ibrutinib (and other BTK 
inhibitors) can be continued during apheresis (all Arms) 
▪ 
radiotherapy can be continued up to apheresis as long as ALC is at least 
100 (all Arms) 
▪ 
all other medication should stop at least 1 week prior to apheresis 
 
Apheresis product for Kymriah is shipped frozen. Cryopreservation must be initiated 
within 24 hours for the end of leukapheresis procedure. 
Apheresis product for Yescarta and Tecartus is shipped fresh within 48 hours after 
apheresis 
Apheresis product for Breyanzi is shipped fresh.  
Apheresis product for ABECMA is shipped fresh.  
 
CAR-T products are manufactured in FDA approved manufacturing facilities   

June 30, 2023 
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6.3 Lymphodepleting chemotherapy  
Prior to CAR-T cell infusion, all patients will receive one cycle of lymphodepleting 
chemotherapy as outlined below. The purpose of this chemotherapy is to induce 
lymphopenia in order to facilitate homeostatic expansion of CAR-T cells.  
The recommended lymphodepleting regimens are: 
 
ARM A – Kymriah (Tisagenlecleucel) for ALL treatment 
Primary regimen: 
-Fludarabine 30 mg/m2 IV daily for 4 days, plus 
-Cyclophosphamide 500 mg/m2  IV daily for 2 days starting with the first 
dose of  fludarabine 
Alternative regimen: 
(For patients with severe hemorrhagic cystitis with prior cyclophosphamide) 
-Cytarabine 500 mg/m2 IV daily for 2 days, plus 
-Etoposide 150 mg/m2 IV daily x 3 days starting with the 1st dose of 
cytarabine 
Infuse Kymriah 2-14 days after completing chemotherapy 
 
ARM B – Yescarta (Axicabtagene) for DLBCL and FL treatment 
Primary regimen: 
-Fludarabine 30 mg/m2 IV daily for 3 days, plus 
-Cyclophosphamide 500 mg/m2 IV daily for 3 days starting with the first 
dose of fludarabine 
Alternative regimen: 
None identified. 
Infuse Yescarta 2-4 days after completing chemotherapy 
 
ARM C – Kymriah (Tisagenlecleucel) for DLBCL treatment 
Primary regimen: 
-Fludarabine 25 mg/m2 IV daily for 3 days, plus 
-Cyclophosphamide 250 mg/m2 IV daily for 3 days starting with the first 
dose of fludarabine 
Alternative regimen: 
(For patients with severe hemorrhagic cystitis with prior cyclophosphamide 
or resistance to a previous cyclophosphamide regimen) 
-Bendamustine 90 mg/m2 IV daily for 2 days 
Infuse Kymriah 2-11 days after completing chemotherapy 

June 30, 2023 
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2017LS118 
 
ARM D – Tecartus (Brexucabtagene Autoleucel) for relapsed or refractory 
Mantle cell lymphoma  
Primary regimen: 
- Cyclophosphamide 500 mg/m2 IV on the fifth, fourth, and third days 
before infusion of TECARTUS.  
- Fludarabine 30 mg/m2 IV on the fifth, fourth, and third days before 
infusion of TECARTUS. 
Alternative regimen: 
None identified. 
 
Arm E: Breyanzi (lisocabtagene maraleucel) for relapsed or refractory large 
B-cell lymphoma 
Primary Regimen: 
-Fludarabine 30 mg/m2 intravenously (IV) for 3 days, plus 
-Cyclophosphamide 300 mg/m2 IV for 3 days starting with the first dose of 
fludarabine 
Infuse BREYANZI 2 to 7 days after completion of lymphodepleting 
chemotherapy. 
Alternative Regimen 
None Identified 
 
ARM F:  Abecma (Idecabtagene Vicleucel) for relapsed or refractory 
multiple myeloma 
Primary Regimen 
-Fludarabine 30 mg/m2 IV daily for 3 days, plus 
-Cyclophosphamide 300 mg/m2 IV daily for 3 days starting with the first 
dose of fludarabine  
Infuse ABECMA 2 days after completion of lymphodepleting chemotherapy.  
May delay up to 7 days for certain conditions (see ABECMA package insert) 
Alternative Regimen 
None identified 
 
ARM G – Tecartus (Brexucabtagene Autoleucel) B-ALL  
Primary regimen: 
Administer a lymphodepleting chemotherapy regimen of: 
- fludarabine 25 mg/m2 intravenously over 30 minutes on the fourth, third, 
and second day before infusion of TECARTUS 

June 30, 2023 
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2017LS118 
-administer cyclophosphamide 900 mg/m2 over 60 minutes on the second 
day before infusion of TECARTUS 
Alternative regimen: 
None identified. 
 
ALL=Acute Lymphoblastic Leukemia, DLBCL=diffuse large B-cell lymphoma, FL follicular 
lymphoma, MM=Multiple Myeloma, B-ALL= B-cell precursor acute lymphoblastic leukemia 
 
Treating investigators should consult with a member of the study team if they wish 
to use an alternative regimen from the above. The dose modification is permitted. 
6.4 CAR-T Infusion Eligibility   
Prior to CAR-T infusion, eligibility must be reconfirmed and documented in the 
CAR-T Epic Order set.  The following criteria must be met: 
6.4.1 DO NOT INFUSE CAR-T CELLS IF (instead delay until the event has resolved):  
6.4.1.1 
There is a significant change in patient status.   
6.4.1.2 
SpO2 sats <91% on RA or using supplemental O2.  
6.4.1.3 
New uncontrolled cardiac arrhythmia.  
6.4.1.4 
Hypotension requiring vasopressor support.  
6.4.1.5 
Uncontrolled, active infection with + culture within 72 hours.   
6.4.1.6 
Rapidly progressing malignancy  
6.4.2 Influenza Testing: All patients will undergo a rapid influenza diagnostic test   
during the months of October through May within 10 days prior to the 
planned CAR-T infusion. If the patient is positive for influenza, he/she 
should complete a full course of oseltamivir phosphate or zanamivir and 
become asymptomatic.   
6.4.3 Performance Status: Patient should not experience a significant change in 
clinical or performance status compared to initial eligibility criteria that 
would, in the opinion of the treating physician, increase the risk of adverse 
events associated with experimental cell infusion. 
6.4.4 Laboratory Abnormalities: Patients experiencing laboratory abnormalities 
after enrollment, that in the opinion of the treating investigator or PI may 
impact subject safety or the subjects’ ability to receive the CAR-T infusion, 
may have their infusion delayed until it is determined to be clinically 
appropriate to proceed with the CAR-T infusion. 
6.4.5 Leukemia Disease Status: Prior to CAR-T infusion and following 
lymphodepleting (LD) chemotherapy patients must not have accelerating 
disease, as this will put them at unacceptable risk for severe CRS. Patients 
should not receive CAR-T infusion if they exhibit significant progression of 

June 30, 2023 
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disease during or following LD chemotherapy as evidenced by: significant 
and increasing circulating blasts, significant increases in organomegaly. 
6.4.6 Lymphoma Disease Status:  Patients should not receive CAR-T infusion if 
they exhibit significant progression of disease during or following LD 
chemotherapy as evidenced by: significant increase in nodal disease, 
significant increases in extranodal areas, occurrence of new lymphoma 
manifestations, or evidenced by significant increase in lymphoma cells in 
blood. 
6.4.7 Infection: CAR-T infusion must be delayed if there is an uncontrolled active 
infection, as evidenced by positive blood cultures for bacteria, fungus, or 
PCR positivity for new viral DNA within 72 hours of CAR-T cell infusion, or 
clinical or radiographic evidence of active infection. Following the 
treatment of a recent infection, significant improvement must be 
established either clinically and/or radiographically, prior to CAR-T 
infusion. 
6.4.8 GVHD Status: Patients should not be infused if they develop Grade 2-4 
acute or extensive chronic GVHD since the time of screening. 
6.4.9 Chemotherapy Toxicity: Patients experiencing toxicities from their 
preceding lymphodepleting chemotherapy will have their infusion 
schedule delayed until these toxicities have been resolved (to Grade 1 or 
baseline).  See section 8.8 for specific prohibited concomitant therapies.  
The specific toxicities warranting delay of CAR-T cell infusion include: 
o 
Pulmonary: Requirement for supplemental oxygen to keep saturation 
greater than 91% or presence of progressive radiographic 
abnormalities on chest x-ray 
o 
Cardiac: New cardiac arrhythmia not controlled with medical 
management. Prior to infusion ECG also required 
o 
Hypotension: requiring vasopressor support 
6.4.10 Prohibited concomitant medications: If patients are taking any of the 
medications listed in package insert, their infusion must be delayed until 
the medications have been stopped. 
6.5 CAR-T Infusion 
  
● All cell doses are independent of patient weight, except for r/r B-Cell ALL 
patients ≤50 kg (KYMRIAH recipients only) 
● Two doses of tocilizumab should be on site prior to CAR-T infusion.  

June 30, 2023 
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2017LS118 
● An attending physician or designated health care provider MUST evaluate 
the patient just prior to CAR-T infusion to ensure the patients meets CAR-T 
infusion criteria.  
● Do NOT use a leukocyte-depleting filter.  
o -  Infuse all contents of the infusion bag.  
o -  Rinse the infusion bag with 10 mL normal saline while maintaining a 
closed tubing system to assure as many cells as possible are infused 
into the patient.  
CAR-T product contains human cells genetically modified with a lentivirus/retrovirus. 
Follow local biosafety universal guidelines applicable for handling and disposal of 
such products to avoid potential transmission of infectious diseases when handling 
the product.   
Premedication:   
All 
patients 
should 
be 
pre-medicated 
with 
acetaminophen 
and  
diphenhydramine.  May repeated every 4-6 hours as needed.   
Steroids should NOT be used for premedication. Therapeutic steroids must be 
stopped >72 hours prior to CAR-T infusion. (Physiological replacement doses are 
allowed:  > 6-12mg /m2/day). No systemic corticosteroids other than physiologic 
replacement of hydrocortisone. 
Cell thawing and infusion of CAR-T product: 
For detailed instructions on the storage, handling, preparation and administration 
of the CAR-T cell product, refer to the KYMRIAH and YESCARTA and TECARTUS and   
Breyanzi and Abecma package Inserts and UM MCT SOP. All used infusion supplies, 
including the infusion bag(s) and tubing, will be disposed of according to the specific 
guidance provided in the Procedure Manual. 
After cell thawing, CAR-T cell product should NOT be washed prior to infusion, and 
all contents will be infused.  
 
KYMRIAH is provided in a single-dose unit containing chimeric antigen receptor 
(CAR)-positive viable T cells  based on the patient weight reported at the time of 
leukapheresis. The entire manufactured product is administered to the patient 
and will be based on data at the time of infusion.  
Adult r/r DLBCL: A single dose of KYMRIAH may contain 0.6 to 6.0 x 108 CAR-
positive viable T cells provided in one or more patient-specific infusion bag(s).  

June 30, 2023 
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2017LS118 
 
Pediatric r/r B-Cell ALL ≤50 kg: A single dose of KYMRIAH may contain 0.2-5.0 x 106 
CAR-positive T cells per kg body weight provided in a single patient-specific 
infusion bag. 
 
Pediatric r/r B-cell ALL >50 kg: A single dose of KYMRIAH may contain 0.1-2.5 x 108 
CAR-positive T cells provided in a single patient-specific infusion bag. 
 
The actual number of CAR-positive T cells in the product is reported on the 
Certificate of Analysis (CoA) that is shipped with KYMRIAH. The volume of CAR-
positive viable T cells in an infusion bag ranges from 10 mL to 50 mL. 
YESCARTA is supplied in an infusion bag (NDC 71287-119-01) containing 
approximately 68 mL of frozen suspension of genetically modified autologous T 
cells in 5% DMSO and 2.5% albumin (human).  
Each bag contains suspension of dose 2 x 106cells CAR positive viable T cells with 
maximum 2x 108 CAR positive viable T-cells.    
Tecartus (Brexucabtagene Autoleucel)   
TECARTUS is supplied in an infusion bag  containing approximately 68 mL of 
frozen suspension of genetically modified autologous T cells in 5% DMSO and  
human serum albumin.  Each TECARTUS infusion bag is individually packed in a 
metal cassette. TECARTUS is stored in the vapor phase of liquid nitrogen and 
supplied in a liquid nitrogen dry shipper. 
 
Infusion Bag NDC number  
Metal Cassette NDC number  
MCL  
71287-219-01  
71287-219-02  
ALL  
71287-220-01  
71287-220-02  
 
Recommended Dosage for MCL 
The target dose is 2 × 106 CAR-positive viable T cells per kg body weight, with a 
maximum of 2 × 108 CAR-positive viable T cells. 
Recommended Dosage for B-ALL 
The target dose is 1 × 106 CAR-positive viable T cells per kg body weight, with a 
maximum of 1 × 108 CAR-positive viable T cells. 
Breyanzi “lisocabtagene maraleucel” 

June 30, 2023 
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2017LS118 
BREYANZI consists of genetically modified autologous T cells, supplied in vials as 
separate frozen suspensions of each CD8 component (NDC 73153-901-08) and 
CD4 component (NDC 73153-902-04). Each CD8 or CD4 component is packed in 
a carton containing up to 4 vials, depending upon the concentration of the 
cryopreserved drug product CAR-positive viable T cells. The cartons for each CD8 
component and CD4 component are in an outer carton (NDC 73153-900-01). 
BREYANZI is shipped directly to the cell lab or clinical pharmacy associated with 
the infusion center in the vapor phase of a liquid nitrogen shipper.  
A single dose of BREYANZI contains 50 to 110 × 106 CAR-positive viable T cells 
(consisting of 1:1 CAR-positive viable T cells of the CD8 and CD4 components),   
with each component supplied separately in one to four single-dose 5 mL vials. 
Each mL contains 1.5 × 106 to 70 × 106 CAR-positive viable T cells. 
Abecma “Idecabtagene Vicleucel” 
ABECMA is supplied in one or more infusion bag(s) (see below) containing a 
frozen suspension of genetically modified autologous T cells in 5% DMSO. A 
single dose of ABECMA contains a cell suspension of 300 to 460 x106 CAR-positive 
T cells in one or more infusion bags 
Each infusion bag of ABECMA is individually packed in a metal cassette. ABECMA 
is stored in the vapor phase of liquid nitrogen and supplied in a liquid nitrogen 
dry vapor shipper.  
•50 mL infusion bag and metal cassette (NDC 59572-515-01) 
•250 mL infusion bag and metal cassette (NDC 59572-515-02) 
•500 mL infusion bag and metal cassette (NDC 59572-515-03) 
 
Breyanzi: 
Once the vials of CAR-positive viable T cells (CD8 component and CD4 component) are 
removed from frozen storage, the thaw must be carried to completion and the cells 
administered within 2 hours. 
• Administration (use CAR-T infusion order set) 
● Confirm the patient’s identity with the patient identifiers on the infusion bag.  
● Thaw before using 

June 30, 2023 
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2017LS118 
● Infusion will be completed within 30 minutes of thawing the cryopreserved 
product in order to preserve maximum cell viability. Use Package Insert for 
an individual product for safe cell infusion. 
● Vital signs (temperature, respiration rate, pulse, pulse oximetry, and blood 
pressure) will be taken prior to, during and immediately after the infusion. 
o  -  Prime the tubing prior to infusion with normal saline.  
● Administer CAR-T as an intravenous infusion at 10 mL to 20 mL per minute, 
adjusted as appropriate for smaller children and smaller volumes. The volume 
in the infusion bag ranges from 10 mL to 50 mL. For BREYANZI  administer 
CD8 component first followed by CD4 component. Use package insert for 
detail. 
• Following CAR-T infusion:  
Should emergency treatment be required in the event of life- threatening 
hypersensitivity or other acute infusion-related reaction, supportive therapy such as 
oxygen, bronchodilators, epinephrine, antihistamines, and corticosteroids should be 
given according to local institutional guidelines. Patients should be evaluated and 
carefully monitored until complete resolution of signs and symptoms. 
Adhere to CAR-T logistics guidelines (Fairview Intranet) for details re pre and post 
CAR-T infusion care. 
6.6 Supportive Care Guidelines 
All patients should receive prophylactic allopurinol, or a non-allopurinol alternative (e.g. 
febuxostat), use rasburicase as medically indicated. The risk of tumor lysis syndrome 
(TLS) is dependent on disease burden. Patients will be closely monitored both before 
and after lymphodepleting chemotherapy and CAR-T infusions including blood tests for 
potassium and uric acid.  
Infection prophylaxis should follow local guidelines and is mainly dictated by the 
preceding lymphodepleting chemotherapy.  
Infection prophylaxis following CAR-T infusion should follow local guidelines for 
neutropenia.   
All blood products administered 6 months following CAR-T should be irradiated.  
Immunosuppressive medications, including steroids, should not be administered unless 
life threatening circumstances arise. 
• Monitoring  

June 30, 2023 
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2017LS118 
● Monitor patients at least daily for 14 days at the certified healthcare facility 
following CAR-T cell infusions for signs and symptoms of CRS and 
neurologic toxicities. (Refer to Appendix II for management guidelines) 
● Instruct patients to remain within proximity of the certified healthcare 
facility (within 45 minutes drive)  for up to 4 weeks following infusion. 
● Patients should be advised not to drive or operate the machinery for 2 
months.  
● Providers will provide patients and caregivers with a Patient Wallet Card 
(required for Yescarta and Kymriah and Tecartus) prior to CAR-T infusion. 
Patient will be informed they need to carry PWC at all times and to share 
it with any Health Care Profession involved in patient’s care.   
Due to the potential for neurologic events, including altered mental status or 
seizures, patients receiving CAR-T19 are at risk for altered or decreased 
consciousness or coordination in the 8 weeks following CAR-T infusion. Advise 
patients to refrain from driving and engaging in hazardous occupations or 
activities, such as operating heavy or potentially dangerous machinery, during this 
initial period. 
 
6.7 Post CAR-T Adverse Reactions 
The following adverse reactions have been observed in patients treated with KYMRIAH 
and YESCARTA and Tecartus and Breyanzi and Abecma and are detailed in package inserts:   
● Cytokine Release Syndrome 
● Neurologic Toxicities (ICANS Immune Effectors Associated Neurotoxicity 
Syndrome) 
● Hypersensitivity Reactions 
● Serious Infections 
● Prolonged Cytopenias 
● Hypogammaglobulinemia  
● Secondary malignancies 
Because of risk of CRS and neurologic toxicities, CAR-T cell products are available only 
through a restricted Risk Evaluation and Mitigation Strategy (REMS) called KYMRIAH 
REMS and YESCARTA & Tecartus and Breyanzi and Abecma REMS.  REMS program to 
manage known or potential serious risks associated with a drug product is required by the 
FDA to ensure that the benefits of the drug outweigh its risks.   The REMS documents are 
available: https://kymriahrems.com/ and www.YescartaTecartusREMS.com or 1-844-

June 30, 2023 
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2017LS118 
454-KITE 
(5483); 
or 
https://www.breyanzirems.com/ 
or 
1-888-423-5436; 
or 
https://www.abecmarems.com/ or   1-888-423-5436 . 
The required components are: 
1. Healthcare facilities that administer CAR-T must be enrolled and comply with 
REMS program 
2. Healthcare facilities must have on-site 2 doses tocilizumab for each patient 
treated  
3. Health care providers who prescribe, dispense and administer CAR-T must be 
trained about the management of CRS and neurologic toxicities 
4. Patients and caregivers are provided for Patient Wallet Card (required for Yescarta 
and Kymriah) 
More detail in package inserts (Appendices I, II, V, VII and VIII).  
6.8 Follow Up 
This protocol outlines recommended treatment guidelines for patients undergoing CAR-
T cell therapies. In the event of disease relapse, disease progression, or other events 
which may require alternative treatment, treating physician discretion will be used in 
determining additional treatment, transfer to another study, or hospice care. Patients will 
continued to be followed in the BMT database for standard transplant related endpoint 
data. 
7 
Management of Selected Expected Toxicities (guided by package insert 
and not considered investigational)  
This study will conform to the Risk Evaluation and Mitigation Strategy (REMS) program to manage 
known or potential serious risks associated with a drug product. This program is required by the 
Food and Drug Administration (FDA) to ensure that the benefits of the drug outweigh its risks. 
The FDA has required a REMS for YESCARTA™ (axicabtagene ciloleucel) and Kymriah™ 
(tisagenlecleucel) and TECARTUS (Brexucabtagene Autoleucel).  
 
The REMS documents are available:  
www.YescartaTecartusREMS.com 
http://www.kymriah-rems.com/ 
https://www.breyanzirems.com/ 
https://www.abecmarems.com/ 
 
Additional Guidance on Management of CAR-T related toxicities can be found in Appendix II 

June 30, 2023 
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2017LS118 
 
7.1 Acute Infusion reaction 
Acetaminophen/paracetamol and diphenhydramine/H1 antihistamine may be repeated 
every 4-6 hours as needed. A course of non-steroidal anti-inflammatory medication may 
be 
prescribed 
if 
the 
patient 
continues 
to have 
fever not 
relieved by 
acetaminophen/paracetamol. 
It 
is 
recommended 
that 
patients 
not 
receive 
corticosteroids at any time, except those already on physiologic replacement therapy, or 
in the case of a life threatening emergency, since this may have an adverse effect on CAR-
T cells. 
 
7.2 Febrile reaction 
In the event of febrile reaction, an evaluation for infection should be initiated, and 
patients managed appropriately with antibiotics, fluids and other supportive care.  
Inpatient treatment is recommended initially. In the event that the patient develops 
sepsis or systemic bacteremia following CAR-T cell infusion, appropriate cultures and 
medical management should be initiated. If a contaminated CAR-T cell product is 
suspected, the product can be retested for sterility using archived samples that are stored 
at the manufacturing site. Consideration of a cytokine release syndrome (see below) 
should be given. 
 
7.3 Cytokine Release Syndrome (CRS) / Macrophage Activation Syndrome 
(MAS) 
Cytokine Release Syndrome (CRS) / Macrophage Activation Syndrome (MAS) are 
expected toxicities of CAR-T therapies. They are reported to present as spectrum 
ranging from grade 1-4. Deaths due to CRS were reported with CAR-T therapies.   
Data from CAR-T treated patients experiencing CRS show marked elevations in IL-6 and 
IFN-g. The symptoms generally occur 1-14 days after cell infusion in patients with ALL and 
may include high fevers, rigors, myalgia/arthralgias, nausea/vomiting/anorexia, fatigue, 
headache, encephalopathy, hypotension, dyspnea, tachypnea and hypoxia. Renal 
failure/renal injury, hyperbilirubinemia and increased ALT or AST can also occur. 
Supportive care and anti-cytokine therapy have been used for effective management of 
CRS. Prompt responses to tocilizumab have been seen in most patients. Several patients 
with a suboptimal response to the first dose of tocilizumab have received a second or 
third dose of tocilizumab with CRS resolution. 
 

June 30, 2023 
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2017LS118 
A detailed treatment algorithm has been established and approved by FDA with clear 
criteria for CRS management and guidance on when to administer tocilizumab and is 
presented in Appendix II.   This guideline was designed to avoid life-threatening toxicities, 
while attempting to allow the CAR-T cells to establish a proliferative phase which appears 
to correlate with tumor response.   
 
The management of CRS is based solely upon clinical parameters as described in Appendix 
II. Serum cytokine and inflammatory marker levels could aid clinical management 
decisions of CRS. 
  
Cases of transient left ventricular dysfunction, as assessed by cardiac ECHO, have been 
reported in some patients with severe CRS (grade 4). Therefore, consideration should be  
given to monitoring cardiac function by cardiac ECHO, during severe CRS, especially in  
cases with prolonged severe hemodynamic instability, delayed response to high dose 
vasopressors, and/or severe fluid overload. 
 
Clinically significant coagulopathy is often seen with moderate to severe CRS (Grade 3 and 
4) and may continue as CRS is beginning to clinically resolve. Coagulation parameters (PT, 
aPTT, and fibrinogen) should be more frequently monitored in this setting. CAR-T 
associated coagulopathy with or without clinical bleeding and hypofibrinogenemia is 
strongly recommended to be managed with cryoprecipitate or fibrinogen concentrate in 
addition to routine blood product support. CAR-T related CRS can be associated with 
neurologic events (Immune Effectors Associated Neurologic Syndrome). 10 point ICANS 
score should be assigned to each patient daily at least for 14 days post CAR-T infusion. 
Two types of neurologic events with respect to timing of onset have been observed.  
Onset of neurologic events can be concurrent with high fevers during the development 
and maximal grade of CRS. Delayed onset of neurologic events can also occur as CRS is 
resolving or after CRS has completely resolved. Consideration should be given to 
monitoring for ICANS  during and after resolution of CRS. 
 
A modification of the Common Terminology Criteria for Adverse Events (CTCAE) version 
5.0 ASTCT CRS and ICANS grading scale is summarized in Appendix II 
 

June 30, 2023 
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2017LS118 
7.4 Neurologic Toxicities (Immune Effectors Associated Neurotoxicity 
Syndrome (ICANS) 
Neurologic toxicities, which may be severe or life-threatening, occurred following 
treatment with CAR-T, including concurrently with CRS, after CRS resolution, or in the 
absence of CRS. 
 
CAR T cell-associated neurotoxicity, occurred in 28% (36/127) of patients receiving 
ABECMA, including Grade 3 in 4% (5/127) of patients. One patient had ongoing Grade 2 
neurotoxicity at the time of death. Two patients had ongoing Grade 1 tremor at the time 
of data cutoff. The median time to onset of neurotoxicity was 2 days (range: 1 to 42 days). 
CAR T cell-associated neurotoxicity resolved in 33 of 36 (92%); For patients who 
experienced neurotoxicity including three patients with ongoing neurotoxicity, the 
median duration of CAR T cell-associated neurotoxicity was 6 days (range: 1 to 578 days). 
Neurotoxicity resolved in 33 patients and median time to resolution was 5 days (range 1 
to 61 days). Thirty-four patients with neurotoxicity had CRS. The onset of neurotoxicity 
during CRS was observed in 29 patients, before the onset of CRS in three patients, and 
after the CRS event in two patients. 
 
The rate of Grade 3 neurotoxicity was 8% in 450 x 106CAR-positive T cells dose cohort and 
1.4% in the 300 x 106CAR-positive T cells dose cohort. The most frequent (greater than or 
equal to 5%) manifestations of CAR T cell-associated neurotoxicity include 
encephalopathy (20%), tremor (9%), aphasia (7%), and delirium (6%). 
Grade 4 neurotoxicity and cerebral edema have been associated with ABECMA in a 
patient in another study in multiple myeloma. Grade 3 myelitis and Grade 3 parkinsonism 
have occurred after treatment with ABECMA in another study in multiple myeloma. 
 
Monitor patients at least daily for 7 days following ABECMA infusion at the REMS-certified 
healthcare facility for signs and symptoms of neurologic toxicities. Rule out other causes 
of neurologic symptoms. Monitor patients for signs or symptoms of neurologic toxicities 
for at least 2 weeks after infusion and treat promptly. Neurologic toxicity should be 
managed with supportive care and/or corticosteroids as needed 
7.5 Tumor  lysis syndrome 
Close monitoring for TLS before and after chemotherapy and CAR-T infusions, including 
blood tests (potassium, uric acid, etc.) will be done as per standard of care.  
 

June 30, 2023 
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2017LS118 
7.6 Graft-Versus-Host Disease (GVHD) 
The chance of GVHD occurring is low, but it is a potential risk with CAR-T therapy.  GVHD 
is an immune-mediated disorder that may occur following allogeneic SCT. Manifestations 
include scleroderma, dry eyes, dry mouth, lichenoid oral changes, bronchiolitis obliterans, 
vanishing bile ducts, or weight loss.  
 
7.7 Infection 
CAR-T should not be administered to patients with active infections or inflammatory 
disorders. Severe, life-threatening, or fatal infections occurred in patients after CAR-T 
infusion. Infections (all grades) occurred in 70% of patients treated with ABECMA. Grade 
3 or 4 infections occurred in 23% of patients. Grade 3 or 4 infections with an unspecified 
pathogen occurred in 15%, viral infections in 9%, bacterial infections in 3.9%, and fungal 
infections in 0.8% of patients. Overall, four patients had Grade 5 infections (3%); two 
patients (1.6%) had Grade 5 events of pneumonia, 1 patient (0.8%) had Grade 5 
bronchopulmonary aspergillosis, and 1 patient (0.8%) had cytomegalovirus (CMV) 
pneumonia associated with Pneumocystis jirovecii. Monitor patients for signs and 
symptoms of infection before and after CAR-T infusion and treat appropriately. 
Administer prophylactic, pre-emptive, and/or therapeutic antimicrobials according to 
standard institutional guidelines. 
 
Febrile neutropenia (was observed in 16% (20/127) of patients after ABECMA infusion 
and may be concurrent with CRS. In the event of febrile neutropenia, evaluate for 
infection and manage with broad-spectrum antibiotics, fluids, and other supportive care 
as medically indicated 
7.8 B cell depletion 
Transient or permanent B cell depletion is a complication with CAR19-T therapy, since 
normal B cells express CD19. This is expected to resolve if and when the CAR19-T cells are 
cleared. CAR19-T related hypogammaglobulinemia is typically managed with 
immunoglobulin replacement therapy dependent upon age specific, disease specific and 
local institutional guidelines. Other potential complications of B cell aplasia include 
progressive multifocal leukoencephalopathy (PML) and reactivation of hepatitis B virus.  
 
• 
Progressive Multifocal Leukoencephalopathy (PML) 
PML is rare but well described with antibody therapies causing B cell aplasia. It is a 
demyelinating disease of the central nervous system, resulting from infection of 
oligodendrocytes and astrocytes, mostly with JC virus.   
 

June 30, 2023 
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2017LS118 
• 
CMV Reactivation 
Cytomegalovirus (CMV) infection resulting in pneumonia and death has occurred 
following CAR19-T administration. Monitor and treat for CMV reactivation in 
accordance with clinical guidelines. 
 
• 
Hepatitis B reactivation 
Reactivation of hepatitis B refers to the abrupt increase in hepatitis B virus (HBV) 
replication in a patient with inactive or resolved hepatitis B. Reactivation can occur 
spontaneously, but more typically is triggered by immunosuppressive therapy of 
cancer, autoimmune disease, or organ transplantation. Patients with evidence of 
reactivated hepatitis B should initiate either tenofovir or entecavir, and pursue 
appropriate consultation. 
 
In general, the risk of hepatitis B reactivation is increased in patients with B cell 
depletion. Patients with latent or active hepatitis B are typically excluded from CAR-
T treatment protocols; however infection could potentially occur following the 
treatment trial completion or early withdrawal. Therefore, patients with a history 
of hepatitis B should be closely monitored for clinical and laboratory signs of active 
HBV infection. Standard guidelines should be followed for the treatment of 
active/reactivated hepatitis B. 
 
7.9 New or secondary malignancies 
There is a theoretical concern that transduction of a patient’s T-cells with CD19 CAR 
lentiviral/retroviral vector could result in an oncogenic effect within these T-cells that 
could result in a T-cell leukemia or lymphoma.  
 
7.10 
Replication-competent lentivirus (RCL) testing 
An RCL may be generated during CAR-T manufacturing or subsequently after introduction 
of vector transduced cells into the patient. However, an RCL resulting from manufacturing 
is highly unlikely since elements are incorporated in the design of the vector system that 
minimize vector recombination and generation of RCL. Furthermore, the vector used to 
transduce the product undergoes sensitive assays for detection of RCL before it can  be 
released to a patient. Thus patients will only receive cell products that meet RCL release 
criteria (as detected by Vesicular Stomatitis Virus/Glycoprotein (VSV-G) qPCR, for 
example).  
 

June 30, 2023 
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2017LS118 
7.11 
Clonality and insertional oncogenesis 
Four of nine treated patients in a gene therapy trial for X-linked Severe Combined 
Immunodeficiency (SCID) developed T cell leukemia 31-68 months post-treatment. The T 
cell leukemias were attributable to clonal expansion conferred by gammaretroviral vector 
integration sites in the CD34+ bone marrow stem cell modification (Hacein-Bey-Abina et 
al 2008). This represents the most severe adverse event caused by vector integration. 
However, there is also evidence for retroviral vector integration site dominance in a gene 
therapy trial of ß-thalasaemia without malignancy (Cavazzana-Calvo et al 2010). The 
lentiviral vector used for Kymriah manufacturing is part of a vector class that may have a 
lower risk for integration in or near oncogenic regions than onco-retroviral vectors 
(Montini E et al 2009). As of February 2018, none of the patients treated with Kymriah 
have developed a new malignancy, T cell or otherwise, related to lentiviral vector 
integration. Subjects should be monitored for malignancy by complete blood count (CBC). 
 
7.12 
Liver safety monitoring 
Following CAR-T infusion, transient and reversible changes in ALT, AST, and total  
bilirubin (TBIL) are typically observed in parallel with the course of cytokine release 
syndrome (CRS). These LFT abnormalities should be followed until return to baseline 
values. If these LFT abnormalities are observed within the first 8 weeks following 
Kymriah infusion and are explicable by CRS, further diagnostic work up is typically not 
warranted. 
 
7.13 
Hemophagocytic Lymphohistiocytosis (HLH)/ Macrophage 
activation syndrome (MAS) 
HLH/MAS occurred in 4% (5/127) of patients receiving ABECMA and lower incidence is 
reported with other CAR19-T cells. One patient treated in the 300 x106CAR-positive T 
cells dose cohort developed fatal multi-organ HLH/MAS with CRS. In another patient 
with fatal bronchopulmonary aspergillosis, HLH/MAS was contributory to the fatal 
outcome. Three cases of Grade 2 HLH/MAS resolved. 
 
The rate of HLH/MAS was 8% in the 450 x106CAR-positive T cells dose cohort and 1% in 
the 300 x106CAR-positive T cells dose cohort. All events of HLH/MAS had onset within 
10 days of receiving ABECMA, with a median onset of 7 days (range: 4 to 9 days) and 
occurred in the setting of ongoing or worsening CRS. Two patients with HLH/MAS had 
overlapping neurotoxicity. 
 

June 30, 2023 
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2017LS118 
HLH/MAS, including life-threatening reactions, occurred following treatment with 
TECARTUS. HLH/MAS occurred in 4% (3/78) of patients with ALL. Two patients 
experienced Grade 3 events and 1 patient experienced a Grade 4 event. The median 
time to onset for HLH/MAS was 8 days (range: 6 to 9 days) with a median duration of 5 
days (range: 2 to 8 days). All three patients with HLH/MAS had concurrent CRS 
symptoms and neurologic events after TECARTUS infusion.  
 
The manifestations of HLH/MAS include hypotension, hypoxia, multiple organ 
dysfunction, renal dysfunction and cytopenia. 
 
HLH/MAS is a potentially life-threatening condition with a high mortality rate if not 
recognized early and treated. Treatment of HLH/MAS should be administered per 
institutional standards. 
 
7.14 
Effects on Ability to Drive and Use Machines 
Due to the potential for neurologic events, including altered mental status or seizures, 
patients receiving CAR-T are at risk for altered or decreased consciousness or 
coordination in the 8 weeks following ABECMA infusion. Advise patients to refrain from 
driving and engaging in hazardous occupations or activities, such as operating heavy or 
potentially dangerous machinery, during this initial period. 
 
7.15 
Side Effects of CAR-T 
Very Common >30% 
Common 10-30% 
Rare 1 -10% 
• Cytokine release 
syndrome  
• Cytokine release 
syndrome, grades 1-2  
• ICANS/Neurotoxicity 
grades 1-2 
• Hypogammaglobulinemia  
• Infection, unspecified 
pathogen 
• Pyrexia 
• Prolonged neutropenia 
• Decreased appetite  
• Headache 
• Encephalopathy 
• CRS and ICANS grade 3-4 
• Increased AST, grades 3-4  
• Hypokalemia, grades 3-4  
• Prolonged thrombocytopenia 
• Viral infection 
• Tachycardia 
• Nausea  
• Diarrhea 
• Vomiting  
• Hypoxia 
• Fatigue 
• Acute kidney injury 
• Hypotension, grades 3-4  
• Increased ALT, grades 3-4  
• Face edema 
• Peripheral edema 
• Chills 
• Fluid overload 
• Back pain 
• Pleural effusion 
• Nasal congestion 
• Pulmonary edema, grades 3-
4 
• Encephalopathy, grades 3-4  
• Fungal infection, grades 3-4  
• Blood and lymphatic system 
disorders: DIC histiocytosis 
lymphocytic 

June 30, 2023 
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2017LS118 
Very Common >30% 
Common 10-30% 
Rare 1 -10% 
• Hypotension 
 
• Increased bilirubin, grades 3-4 
• Delirium  
• Hypophosphatemia, grades 3-4 
• Hypertension 
• Bacterial infection  
• Cough  
• Constipation  
• Viral infection, grades 3-4  
• Hypoxia, grades 3-4 
• Prolonged neutropenia, Day 56 
• Infection, unspecified pathogen, 
grades 3-4  
• Hypofibrinogenemia with grades 
3-4 CRS  
• Abdominal pain 
• Pain in extremity 
• Pulmonary edema 
• Decreased appetite, grades 3-4 
• Pyrexia, grades 3-4  
• Myalgia 
• Fungal infection 
• Anxiety 
• Bacterial infection, grades 3-4  
• Acute kidney injury, grades 3-4  
• Prolonged thrombocytopenia, 
Day 56  
• Arthralgia 
• Tachypnea 
hemophagocytosis, 
coagulopathy 
• Investigations: Blood 
creatinine increased, aPTT 
prolonged  
• Respiratory, thoracic, and 
mediastinal disorders: 
Respiratory distress, 
respiratory failure, acute RDS 
• Cardiac disorders: Cardiac 
arrest, cardiac failure 
• Metabolism and nutrition 
disorders: Tumor lysis 
syndrome 
• Vascular disorders: Capillary 
leak syndrome 
• General disorders and 
administration site 
conditions: Multiple organ 
dysfunction syndrome 
• Nervous System: Intracranial 
hemorrhage, seizure 
• Gastrointestinal disorders: 
Abdominal compartment 
syndrome  
• Immune system disorders: 
GVHD  
• CMV re-activation  
• PC pneumonia 
 
 
8 
Clinical Care Activities 
Scheduled evaluations after screening and until day 28 may be performed +/-3 days from the 
targeted date; assessments performed after day 28 and through 3 months may be done +/-14 
days of the targeted date.  After 3 month assessments may be done +/- 28 days of the targeted 
date.  In addition, targeted days may be altered as clinically appropriate. Any modifications or 
omissions to the clinical care activities will not be considered protocol deviations. 

May 26, 2021 
Page 59 of 74 
2017LS118 
 
 
 
Screening 
(week -16 
to week -
12) 
Prior to 
Chemo 
(Day -14 to  
-2) 
Prior 
to 
CAR-
T 
Infusio
n 
(Day 0) 
D 
4 
D 7 
D 
11 Ŧ 
D 
14 
D 17Ŧ 
D 
21 
D 
28 
D 60 
3 
Month 
6 
month 
9 
months 
12 
month 
18 
Month 
Yearly 
through 
15 years 
Obtain Informed 
Consent  
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Obtain written 
acknowledgment of 
“MEDICATION 
GUIDE”for Yescarta 
only ỻ 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Patient history 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion 
criteria 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Confirm CD19 
expression on bx  for 
lymphoma /leukemia 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical History  
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
X 
x 
x 
x 
x 
 
 
Annual Survival Data as 
required by FDA 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
x 
 
x 
Prior antineoplastic 
therapy 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Donor chimerism (prior 
allogeneic SCT patients 
only) 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical examination 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
x 
x 
 
x 
 
 
Performance status 
x 
x 
 
x 
 
 
 
 
 
 
x 
 
x 
x 
 
x 
 
 
Height 
x 
 
 
 
 
 
 
 
 
 
 
 
 
x 
 
x 
 
 
Weight 
x 
x 
xƱ 
xƱ 
xƱ 
xƱ 
xƱ 
xƱ 
xƱ 
xƱ 
x 
xƱ 
x 
x 
xƱ 
x 
 
xƱ 
Vital signs 
x 
x 
 
x 
x 
x 
x 
x 
x 
x 
x 
 
x 
x 
 
x 
 
 
Pulse oximetry 
x 
 
 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Intervention 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Lymphodepleting 
Chemotherapy 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CAR-T cell infusion 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

June 30, 2023 
Page 60 of 74 
2017LS118 
 
 
 
Screening 
(week -16 
to week -
12) 
Prior to 
Chemo 
(Day -14 to  -
2) 
Prior 
to 
CAR-
T 
Infusion 
(Day 0) 
D 
4 
D 
7 
D 
11 Ŧ 
D 
14 
D 17Ŧ 
D 
21 
D 
28 
D 
60 
3 
month 
6 
month 
9 
month 
12 
month 
18 
month 
Yearly 
through 
15 years 
Laboratory assessments 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hematology (CBC/diff) 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
2 years 
Chemistry (CMP) 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
2 years 
 (ferritin, LDH, CRP) 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
 
 
Serum pregnancy test 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
HIV test 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hepatitis B and C serology 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Influenza PCR 
 
Within 10 days of infusion 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Coagulation factors (PT, 
aPTT, INR, fibrinogen, D-
dimer) 
X 
 
 
X 
x 
x 
x 
x 
x 
x 
x 
 
 
 
 
 
 
 
Serum  
immunoglobulin levels 
(IgG) 
x 
 
 
X 
 
 
 
 
 
 
x 
x 
x 
x 
x 
x 
 
X 
X 
CMV Ag  
 
 
 
X 
 
X 
 
X 
 
 
X 
X 
X 
 
 
 
 
 
ECHO 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Electrocardiogram (ECG) 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
T Cell Subset Extended 
Profile (includes  CD4 and 
CD19 B-cells l) 
 
 
 
x 
 
 
 
 
 
 
x 
x 
x 
x 
 
x 
 
 
Uric Acid 
X 
 
 
x 
x 
x 
x 
x 
x 
x 
x 
 
 
 
 
 
 
 
Clonoseq Adaptive * 
X (ID) 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
Additional Laboratory assessments for Kymriah (PEDS only) 
T Cell Subset Extended 
Profile (includes B-cell 
lymphocyte subset) 
X 
 
 
x 
 
 
 
 
 
 
x 
Monthly Through 2 years 
 
Hematology (CBC/diff) 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
Monthly Through 2 years  
2 years 
Serum  
immunoglobulin levels 
(IgG) 
x 
 
 
X 
 
 
 
 
 
 
x 
Monthly Through 2 years 
x 

June 30, 2023 
Page 61 of 74 
2017LS118 
Ŧ Optional, per Treating physician recommendation 
¥ Adults, only if history of CNS disease 
ß(If PET denied by insurance, a CT CAP+neck with IV contrast can be done) 
Ʊ Peds only regardless of CNS disease history 
& - If PET CT denied by insurance, a skeletal survey can be done 
ỻ All Medication Guides can be found  in the  drug package inserts  
 
*Adaptive testing is optional for NHL and ALL (logistics TBD)
 
Screening 
(week -16 
to week -
12) 
Prior to 
Chemo 
(Day -14 to  -
2) 
Prior 
to 
CAR-
T 
Infusion 
(Day 0) 
D 
4 
D 
7 
D 
11 Ŧ 
D 
14 
D 
17Ŧ 
D 
21 
D 28 
D 
60 
3 
Month 
6 
month 
9 
month 
12 
month 
18 
month  
Yearly 
through 
15 years 
Disease Assessments for ALL  
Bone marrow biopsy:  
morphology, flow 
cytometry (leukemia/ 
lymphoma evaluation), 
FISH, cytogenetics & MRD 
tracking through NGS  
x (anytime 
prior to 
car-t 
infusion) 
 
 
 
 
 
 
 
 
 
x 
X 
x 
x 
X Ʊ 
x 
X 
2 years 
Lumbar puncture: 
WBC/diff, total protein, 
glucose, RBC, 
leukemia/lymphology 
evaluation, and cytology 
X (if 
symptoms) 
X (if 
symptoms) 
 
 
 
 
 
 
 
 
x 
X Ʊ  
x¥,  Ʊ 
x¥,  Ʊ 
X Ʊ 
x 
X 
2 years 
Disease Assessments for Lymphoma 
PET/CT ß  or CT or PET  ß 
Whole Body  (lymphoma 
only) 
x (anytime 
prior to 
car-t 
infusion) 
x 
 
 
 
 
 
 
 
 
X 
(PET 
only) 
ß  
 
X 
(PET/
CT)ß 
X (CT) 
X (CT)   
x (CT)  
X(CT) 
2 years 
(CT) 
Disease Assessments for Myeloma Only 
SPEP, UPEP, 
Kappa/Lambda light 
chains, Immunofixation, 
LDH, B2 microglobulin 
x 
 
 
 
 
 
 
 
 
 
X 
X 
X 
X 
X 
X 
 
2 years 
Bone marrow biopsy 
X (ok after apheresis) 
 
 
 
 
 
 
 
 
 
 
X 
X 
 
X 
 
2 years 
PET  
X (ok after apheresis) 
 
 
 
 
 
 
 
 
 
 
X 
 
 
X 
 
2 years 

May 26, 2021 
Page 62 of 74 
2017LS118 
 
8.1 Optional Research Samples 
Subjects will be given the option to co-enroll on study MT2017-12, “Monitoring of 
Immune and Microbial Reconstitution in Hematopoietic Cell Transplantation (HCT) 
and Novel Immunotherapies” to provide research sample collection.   
9 
Adverse Event Monitoring, Documentation, and Reporting 
Toxicity and adverse events will be classified according to NCI's Common Terminology 
Criteria for Adverse Events V 5.0 (CTCAE) and reported on the schedule below. A copy of 
the 
CTCAE 
can 
be 
downloaded 
from 
http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm#ctc_50.   
Treatment related outcomes and events will be recorded in the Blood and Marrow 
Transplantation (BMT) database and CIBMTR. 
9.1 
Event Monitoring 
Event monitoring will be performed by the patient’s clinical care team. 
9.2 
Event Documentation  
Targeted toxicity may be documented as CARTOX note at every visit in EMR by a 
clinical team, or in the daily notes. CARTOX screening assessments will be 
performed through at least day 14. 
Treatment related outcomes and events will be recorded in the Blood and Marrow 
Transplantation (BMT) database.  
Events requiring prompt reporting to the University of Minnesota Institutional 
Review Board (IRB), early stopping rule events (treatment related mortality before 
day 100), and protocol deviations will be documented in OnCore.  Refer to section 
9.3 for reporting requirements.  
 
 

June 30, 2023 
Page 63 of 74 
2017LS118 
9.3 
Event Reporting  
Agency 
Criteria for reporting 
Timeframe 
Form to Use 
Submission address/ 
fax numbers 
U of MN 
IRB 
Events requiring prompt reporting including, but not 
limited to unanticipated death of a locally enrolled 
subject(s); new or increased risk; any adverse event  that 
require a change to the protocol or consent form or any 
protocol deviation that resulting in harm  For a complete 
list refer to 
http://www.research.umn.edu/irb/guidance/ae.html#.V
C7xraI0-sh  
Within 5 
business days 
of event 
discovery 
 
Report Form 
ETHOS Portal 
 
Masonic 
Cancer 
Center SAE 
Coordinator 
Events that impact the early study stopping rules – 
treatment related morality before day 100 (section 
11.4). 
At time of 
reporting 
Event Form 
SAE Coordinator 
mcc-saes@umn.edu 
CIBMTR 
Required: 
• 
CRS (all grade) 
• 
Neurologic Toxicities (all grades) 
Encouraged: 
• 
AEs and SAEs 
BMT Database 
will report per 
CIBMTR SOP 
CIBMTR Form 
Online into FormsNet3 
(CIBMTR’s EDC) 
FDA for 
Novartis 
product 
• Patient death 
• Unexpected SAEs 
At time of 
reporting 
MedWatch 
website 
www.fda.gov/
medwatch 
 
Report to the FDA 
directly by calling 
1-800-FDA-1088 
• As part of REMS CAR-T requires reporting of known 
AE’s of CRS and Neurotoxicities:  CIBMTR Summary 
forms (sent back to center from CIBMTR) 
Every 3 
months  
CIBMTR 
summary  
 
CIBMTR will Report to 
Novartis  
 
Site may report to 
Novartis by calling 
1-888-669-6682 
FDA for Kite 
products 
(Yescarta & 
Tecartus)  
• Patient death 
• Unexpected SAEs 
At time of 
reporting 
MedWatch 
website 
www.fda.gov/
medwatch 
Report to the FDA 
directly by calling 
1-800-FDA-1088 
• CIBMTR Summary forms (sent back to center from 
CIBMTR) 
Every 3 
months  
CIBMTR 
summary 
CIBMTR will report to 
Kite  
 
Site may report to 
Kite by calling 
1-844-454-KITE 
FDA for 
Bristol 
Meyer 
Squibb 
products 
• 
Patient death 
• 
Unexpected SAEs 
• 
CIBMTR Summary forms (sent back to center 
from CIBMTR) 
 
www.fda.gov/
medwatch. 
To report SUSPECTED 
ADVERSE REACTIONS, 
contact Bristol-Myers 
Squibb at 1-888-805-
4555 or FDA at 1-800-
FDA-1088  

June 30, 2023 
Page 64 of 74 
2017LS118 
All stem cell transplant/therapy patients co-enroll on standard data-collection and 
long term data storage protocols. 
The SAE Coordinator will provide the Masonic Cancer Center’s Data and Safety 
Monitoring Council (DSMC) with the SAE in an appropriate format depending on 
the individual SAE (as reported or in a summary format). 
10 
Study Data Collection and Monitoring 
10.1 
Data Collection  
This study will track events requiring prompt reporting to the IRB, stopping rule 
events, and clinical deviations using University of Minnesota CTSI’s instance of 
OnCore® (Online Enterprise Research Management Environment). 
The Oncore database resides on dedicated secure and PHI compliant hardware 
consisting of 3 physical servers: dev, DR, and production. The dev server is located 
in the University of Minnesota (UMN) datacenter (WBOB) and houses six database 
instances (test, train, sandbox, mcc reports, oncdm, and vendor) that are backed 
up locally because the data is refreshed from Oncore production data. The 
production server is located in the UMN datacenter (WBOB). All the data servers 
are managed by the Academic Health Center – Information Systems (AHC-IS) 
virtual servers which utilize clustered infrastructure to provide real-time failover 
of virtual servers. This real-time clustering is physically limited to the UMN data 
center. All relevant AHC IS procedures related for PHI compliant servers (as 
required by the Center of Excellence for HIPAA Data) apply to Oncore databases. 
 The integrated data will be stored in PHI compliant servers managed by AHC IS 
with access given to those authorized users in the Clinical and Translation Science 
Institute Informatics team (CTSI BPIC and MCC CISS). The data will be integrated 
and extracted to researchers through the CTSI Informatics team and will be 
(Breyanzi 
and 
Abecma) 
Kymriah for 
ALL 
(Outcomes 
based 
contract 
agreement 
in place) 
No remission on day 28 bone marrow biopsy  
(determined by PI or designee)  
Between day 
38-35 after 
Kymriah 
infusion 
Kymriah Care 
Hub  
Report to Novartis by 
calling  
1-888-669-6682 

June 30, 2023 
Page 65 of 74 
2017LS118 
delivered through secure and compliant mechanisms (e.g. AHC IE data shelter, 
BOX, sftp, etc). If data de-identification is needed, then compliant AHC IE data de-
identification tools will be used. The informatics team will grant the IRB approved 
study team members access to data. 
Key study personnel are trained on the use of OnCore and will comply with 
protocol specific instructions embedded within the OnCore. 
All treatment related outcomes and complications will be recorded in the Blood 
and Marrow Transplantation (BMT) database. 
10.2 
Data and Safety Monitoring  
The study’s Data and Safety Monitoring Plan will be in compliance with the 
University of Minnesota Masonic Cancer Center's Data & Safety Monitoring Plan 
(DSMP), which can be accessed at http://z.umn.edu/dmsp. 
For the purposes of data and safety monitoring, this phase II study is classified as 
moderate risk.  Therefore the following requirements will be fulfilled: 
 
The Masonic Cancer Center Data and Safety Monitoring Council (DSMC) will 
review the trial’s progress twice yearly 
 
The PI will comply with at least twice yearly monitoring of the project by the 
Masonic Cancer Center monitoring services. 
 
The PI will oversee the submission of all reportable adverse events per the 
definition of reportable in section 9.3 to the Masonic Cancer Center’s SAE 
Coordinator and the University of Minnesota IRB.   
 
In addition, at the time of the continuing review with the University of Minnesota 
IRB, a copy of the report with any attachments will be submitted to the Cancer 
Protocol Review Committee (CPRC). 
10.3 
Study Related Monitoring  
The investigator will permit study-related monitoring, audits, and inspections by 
the IRB, government regulatory bodies, and University of Minnesota compliance 
groups.  The investigator will make available all study related documents (e.g. 
source documents, regulatory documents, data collection instruments, study 
data, etc.).  The investigator will ensure the capability for inspections of applicable 
study-related facilities (e.g. pharmacy, diagnostic laboratory, etc.) will be available 
for trial related monitoring, audits, or regulatory inspections. 

June 30, 2023 
Page 66 of 74 
2017LS118 
10.4 
Record Retention  
The investigator will retain study records for at 6 years after the study file is closed 
with the IRB and FDA.   
In addition, the Clinical Trials Office (CTO) will keep a master log of all patients 
participating in the study with sufficient information to allow retrieval of the 
medical records for that patient.  
Please contact the CTO before destroying any study related records. 
11 
Statistical Consideration 
This is a phase II study using FDA-approved CAR-T products for patients with hematologic 
malignancies. Patient will be assigned to Arms (A B, C, D, E,F and G) based on age, CAR-T 
product and diagnosis. Overall remission rate, safety events and other endpoints will be 
calculated for Arm A, B, C D, E, E and G separately.  
 
Arm A: Relapsed or refractory pediatric CD19+ B-cell Acute Lymphoblastic Leukemia; age 
0 to ≤ 25 years at the time of infusion and Kymriah product.  
 
Arm B: Adults (≥18 years) with relapsed or refractory large B-cell lymphoma and follicular 
lymphoma after two or more lines of systemic chemotherapy and Yescarta product 
 
Arm C: Adult patients (≥18 years) with Refractory diffuse large B cell lymphoma and 
Kymriah product 
 
Arm D: Adults (≥18 years) with relapsed or refractory mantle cell lymphoma receiving 
Tecartus product 
 
Arm E: Adults  (≥18 years) with relapsed or refractory large B-cell lymphoma receiving 
Breyanzi “lisocabtagene maraleucel” 
 
Arm F: Adults  (≥18 years) with relapsed or refractory multiple myeloma receiving Abecma 
“Idecabtagene Vicleucel” 
 
Arm G: Adults  (≥18 years) with B-ALL receiving Tecartus product (Brexucabtagene 
Autoleucel) 
 

June 30, 2023 
Page 67 of 74 
2017LS118 
11.1 
Primary  Endpoint 
The primary endpoint for Arm A is the composite rate of complete remission (CR) and CRi 
(without count recovery) rate at day 28. 
 
The primary endpoint for Arm B is the Overall Response Rate (complete response + Partial 
response by Lugano) (ORR) separately for DLBCL and FL.  
 
The primary endpoint for Arm C is the Overall Response Rate (complete response + Partial 
response by Lugano) (ORR). 
 
The primary endpoint for Arm D is the Overall Response Rate (complete response + Partial 
response by Lugano) (ORR). 
 
The primary endpoint for Arm E is the Overall Response Rate (complete response + Partial 
response by Lugano) (ORR). 
 
The Primary objective for Arm F is to estimate the Overall Response Rate (complete 
response + Partial response by IMWG criteria) (ORR). 
 
The Primary objective for Arm G is the composite rate of complete remission (CR) and CRi 
(without count recovery) rate at day 28. 
 
 
  
11.2 
Secondary Endpoints 
Secondary endpoints for Arm A and G include the following: 
• The proportion of patients with MRD-negative CR (or CRi). 
 
Secondary endpoints for all Arms include the following: 
• Treatment related mortality (in absence of disease relapse/progression) at day 
28, day 100 and 1 year.   
• The Relapse-free Survival (RFS) as evaluated by the time of achievement of 
complete remission to relapse or death. 
• The event-free survival (EFS) from the date of the CAR-T infusion through 1 year 
post treatment. 
• Overall Survival (OS) from the date of the CAR-T infusion through the date of 
patient death for any reason. 

June 30, 2023 
Page 68 of 74 
2017LS118 
• The proportion of patients developing grade 3, 4 targeted toxicity of CRS and/or 
neurotoxicity.   
11.3 Analysis of Primary and Secondary Endpoints 
The analysis will be done for Arm A, B, C, D, E,  F and G separately. The binary endpoints 
such as CR, CRi rate, composite rate of CR and CRi rate, MRD-negative CR, ORR, Complete 
Remission rate by Lugano criteria and proportion of patients who are alive but not in 
remission at day 28, summary statistics including proportions and their 95% confidence 
intervals will be calculated. Safety of CAR-T therapy assessments including grade 3 and 4 
targeted toxicity of CRS and/or neurotoxicity will be presented in the data listings and 
summarized with descriptive statistics.  
Kaplan-Meier curves will be used to estimate event free survival (EFS), overall survival 
(OS) and relapse-free survival (evaluated by the time of achievement of CR/PR to relapse 
or death) with 95% confidence interval. Treatment related mortality at day 28, 100 and 1 
year, will be estimated with 95% confidence interval by competing risk analysis treating 
relapse, disease relapse/progression as the competing risk.  
All analyses will be conducted using SAS software (SAS Institute Inc., Cary, NC).  Results 
will be deemed statistically significant at the 0.05 significance level unless otherwise 
specified. 
11.4 Sample Justification and Accrual 
For Arm A, sixty patients will achieve 99.9% power to detect a difference of overall 
remission rate (ORR) between null hypothesis (ORR) of 40% and alternative hypothesized 
rate of 70%. For Arm B, sixty patients will achieve 88.5% power to detect a difference of 
overall remission rate (ORR) between null hypothesis (ORR) of 40% and alternative 
hypothesized rate of 60%. For Arm C, sixty patients will achieve 89.2% power to detect a 
difference of overall remission rate (ORR) between null hypothesis (ORR) of 35% and 
alternative hypothesized rate of 55%. For Arm D, sixty patients will achieve 99.9% power 
to detect a difference of overall remission rate (ORR) between null hypothesis (ORR) of 
40% and alternative hypothesized rate of 75%. For Arm E, sixty patients will achieve 90% 
power to detect a difference of overall remission rate (ORR) between null hypothesis 
(ORR) of 30% and alternative hypothesized rate of 50%. For Arm F, sixty patients will 
achieve 89% power to detect a difference of overall remission rate (ORR) between null 
hypothesis (ORR) of 50% and alternative hypothesized rate of 70%. For Arm G, sixty 
patients will achieve 88.5% power to detect a difference of overall remission rate (ORR) 
between null hypothesis (ORR) of 40% and alternative hypothesized rate of 60%. The 
power calculations were based on two-sided exact test with a significance level of 0.05 
(PASS15, NCSS, LLC).  

June 30, 2023 
Page 69 of 74 
2017LS118 
 
Based on prior enrollment, we expect to accrue approximately 15 patients per arm 
B,C,D,E, F and about 10 patient per arm A and G per year.  
11.5 Early Stopping Rule for Excessive Toxicity during Expansion Component 
Stopping rules will be employed to monitor excess toxicity for the seven arms separately. 
The stopping rule was developed using Pocock stopping boundaries. [1] 
 
Excess toxicity will be defined as TRM by day 100 post infusion. The goal is to construct a 
boundary based on toxicity such that the probability of early stopping is at most 10% if 
the toxicity rate is equal to 20%. Given these parameters, the upper stopping boundary 
for toxicity is 3 out of 3, 4 out of 6, 5 out of 9, 6 out of 12, 7 out of 16, 8 out of 19, 9 out 
of 22, 10 out of 26, 11 out of 30, 12 out of 33, 13 out of 37, 14 out of 41, 15 out of 45, 16 
out of 49, 17 out of 53, 18 out of 57, and 19 at any time. If the true toxicity rate is as high 
as 40% then chance of early stopping is 96% and the expected sample size is 4.2.  
12 
Conduct of the Study 
12.1 Good Clinical Practice 
The study will be conducted in accordance with the appropriate regulatory 
requirement(s).  Essential clinical documents will be maintained to demonstrate 
the validity of the study and the integrity of the data collected.  Master files should 
be established at the beginning of the study, maintained for the duration of the 
study and retained according to the appropriate regulations.   
12.2 Ethical Considerations 
The study will be conducted in accordance with ethical principles founded in the 
Declaration of Helsinki.  The IRB will review all appropriate study documentation 
in order to safeguard the rights, safety and well-being of the patients.  The study 
will only be conducted at sites where IRB approval has been obtained.  The 
protocol, consent, written information given to the patients, safety updates, 
annual progress reports, and any revisions to these documents will be provided to 
the IRB by the investigator.   
12.3 Informed Consent 
All potential participants will be given a copy of the IRB-approved Consent to 
review. The investigator or designee will explain all aspects of the treatment in lay 
language and answer all questions regarding the treatment. If the participant 
decides to participate, he/she will be asked to sign and date the Consent 

June 30, 2023 
Page 70 of 74 
2017LS118 
document. Patients who refuse to participate or who withdraw will be treated 
without prejudice. 
13 
References 
1. CD19-targeted chimeric antigen receptor T-cell therapy for acute lymphoblastic leukemia. 
Maude SL, Teachey DT, Porter DL, Grupp SA. Blood. 2015 Jun 25;125(26):4017-23. 
2. Chimeric antigen receptor T cells for sustained remissions in leukemia. Maude SL, Frey N, 
Shaw PA, Aplenc R, Barrett DM, Bunin NJ, Chew A, Gonzalez VE, Zheng Z, Lacey SF, 
Mahnke YD, Melenhorst JJ, Rheingold SR, Shen A, Teachey DT, Levine BL, June CH, Porter 
DL, Grupp SA N Engl J Med. 2014 Oct 16;371(16):1507-17. 
3. Kymriah and Yescarta package inserts. 
4. Neelapu SS, Locke FL, Bartlett NL, Lekakis LJ, Miklos DB, Jacobson CA, et al. Go 
WY.Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma.N 
Engl J Med. 2017 Dec 28;377(26):2531-2544. doi: 10.1056/NEJMoa1707447. Epub 2017 
Dec 10. 
5. Daniel W. Lee, Rebecca Gardner, David L. Porter, Chrystal U. Louis, Nabil Ahmed, Michael 
Jensen, Stephan A. Grupp and Crystal L. Mackall. Current concepts in the diagnosis and 
management of cytokine release syndrome Blood 2014 124:188-195; doi: 
https://doi.org/10.1182/blood-2014-05-552729 
6. Ivanova, A., Qaqish, B.F., and Schell, M.J. (2005). Continuous toxicity monitoring in phase 
II trials in oncology. Biometrics 61: 540-545. 
7. Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia.   
Maude et al.  NEJM. 2018 N Engl J Med. 2018 Feb 1;378(5):439-448. 
8. TECARTUS package insert. https://www.fda.gov/media/140409/download. 
9. Breyanzi package insert. https://www.fda.gov/media/145711/download 
10. Abecma package insert. https://www.fda.gov/media/147055/download 
11. Caron A. Jacobson, Julio C. Chavez, Alison R. Sehgal, Basem M. William, Javier Munoz, 
Gilles A. Salles, et al. Interim analysis of ZUMA-5: A phase II study of axicabtagene 
ciloleucel (axi-cel) in patients (pts) with relapsed/refractory indolent non-Hodgkin 
lymphoma (R/R iNHL). Journal of Clinical Oncology 2020 38:15_suppl, 8008-8008 
12. Jeremy S Abramson, MD, M Lia Palomba, MD, Prof Leo I Gordon, MD, Matthew A Lunning, 
DO, Prof Michael Wang, MD, Jon Arnason, MD, et al. Lisocabtagene maraleucel for 
patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): a 
multicentre seamless design study. The Lancet, Volume 396, Issue 10254, P839-852, 
September 19, 2020. 
13.   Munshi NC, Anderson LD Jr, Shah N, et al. Idecabtagene vicleucel in relapsed and 
refractory multiple myeloma. N Engl J Med. 2021;384(8):705-716. 

June 30, 2023 
Page 71 of 74 
2017LS118 
 
APPENDIX I  - Performance Status Scales 
 
GRADE 
ECOG PERFORMANCE STATUS 
0 
Fully active, able to carry on all pre-disease performance without 
restriction 
1 
Restricted in physically strenuous activity but ambulatory and able to 
carry out work of a light or sedentary nature, e.g., light house work, 
office work 
2 
Ambulatory and capable of all selfcare but unable to carry out any work 
activities; up and about more than 50% of waking hours 
3 
Capable of only limited selfcare; confined to bed or chair more than 50% 
of waking hours 
4 
Completely disabled; cannot carry on any selfcare; totally confined to 
bed or chair 
5 
Dead 
Ref: Oken M, Creech R, Tormey D, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group.Am J Clin 
Oncol. 1982;5:649-655. 
Karnofsky Performance Status Scale (≥ 16 years) 
Able to carry on normal activity and to work; no special 
care needed. 
  100   
Normal no complaints; no evidence of disease. 
90 
Able to carry on normal activity; minor signs or 
symptoms of disease. 
80 
Normal activity with effort; some signs or 
symptoms of disease.  
Unable to work; able to live at home and care for most 
personal needs; varying amount of assistance needed. 
70 
Cares for self; unable to carry on normal activity or 
to do active work. 
60 
Requires occasional assistance, but is able to care 
for most of his personal needs. 
50 
Requires considerable assistance and frequent 
medical care.  
Unable to care for self; requires equivalent of 
institutional or hospital care; disease may be 
progressing rapidly. 
40 
Disabled; requires special care and assistance. 
30 
Severely disabled; hospital admission is indicated 
although death not imminent. 
20 
Very sick; hospital admission necessary; active 
supportive treatment necessary. 
10 
Moribund; fatal processes progressing rapidly. 
0 
Dead 

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Lansky Score (children < 16 years) 
Lansky Score 
Performance Status 
100 
Fully active, normal 
90 
Minor restrictions in physically strenuous activity 
80 
Active, but tires more quickly 
70 
Both greater restriction of and less time spent in play activity 
60 
Up and around, but minimal active play; keeps busy with quieter activities 
50 
Gets dressed but lies around much of the day, no active play but able to participate in all quiet play 
and activities 
40 
Mostly in bed; participates in quiet activities 
30 
In bed; needs assistance even for quiet play 
20 
Often sleeping; play entirely limited to very passive activities 
10 
No play; does not get out of bed 
0 
Unresponsive 
 
 

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APPENDIX II - Management Of Adverse Events 
 
Steps to diagnose and manage CRS, CRES and related toxicities can be found at the following 
link: 
http://intranet.fairview.org/fv/groups/intranet/documents/bmtprotocol/s_148596.pdf 
 
 

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