A Randomized, Open-Label, Phase 2 Study Evaluating Lymphodepletion With ALLO-647, Fludarabine, and Cyclophosphamide, vs. Fludarabine and Cyclophosphamide Alone, in Subjects With Relapsed/Refractory Large B-Cell Lymphoma Receiving ALLO-501A Allogeneic CAR T Cell Therapy
Phase: PHASE2
Conditions: Relapsed/Refractory Large B Cell Lymphoma
Sponsor: Allogene Therapeutics

ALLO-647 
EXPAND Study 
Protocol ALLO-647-201 (Amendment 1) 
 
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A RANDOMIZED, OPEN-LABEL, PHASE 2 STUDY EVALUATING 
LYMPHODEPLETION WITH FLUDARABINE, CYCLOPHOSPHAMIDE, AND 
ALLO-647, VS. FLUDARABINE AND CYCLOPHOSPHAMIDE ALONE, IN 
SUBJECTS WITH RELAPSED/REFRACTORY LARGE B-CELL LYMPHOMA 
(LBCL) RECEIVING ALLO-501A ALLOGENEIC CAR T CELL THERAPY 
Investigational Product Number: 
ALLO-647 / ALLO-501A  
Investigational Product Name: 
Not Applicable  
NCT #: 
<<TBD>> 
CTIS/CT 
2022-502197-17-00 
Protocol: 
Protocol No. 
EXPAND Study 
ALLO-647-201 
Phase: 
Phase 2 
Date: 
13 October 2022 
Protocol Version 
Amendment 1 
Clinical Study Sponsor:   
Allogene Therapeutics Inc.   
210 E. Grand Ave 
South San Francisco, CA 94080 
 
Key Sponsor Contacts: 
 
Medical Director, Clinical Development 
 
Email: 
 
Phone: 
 
 
 
Associate Director, Clinical Operations 
 
Email:
 
 
Phone:  
 
This document and accompanying materials contain confidential information belonging to Allogene. Except as otherwise agreed to in 
writing, by accepting or reviewing these documents, you agree to hold this information in confidence and not copy or disclose it to 
others (except where required by applicable law) or use it for unauthorized purposes. In the event of any actual or suspected breach of 
this obligation, Allogene must be promptly notified. 
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TABLE OF CONTENTS 
LIST OF TABLES .....................................................................................................................8 
LIST OF FIGURES ...................................................................................................................8 
OVERVIEW OF CHANGES ....................................................................................................9 
PROTOCOL SYNOPSIS ........................................................................................................12 
1. INTRODUCTION ..............................................................................................................17 
1.1 
Mechanism of Action/Indication .....................................................................17 
1.2 
Background and Rationale ...............................................................................17 
1.2.1 
Non-Hodgkin Lymphoma .................................................................17 
1.2.2 
Large B-cell Lymphoma ....................................................................17 
1.2.3 
Chimeric Antigen Receptor T cells ...................................................18 
1.2.4 
Lymphodepletion Regimen Including ALLO-647 ............................18 
1.2.4.1 Fludarabine and Cyclophosphamide .......................................20 
1.2.4.2 ALLO-647 ...............................................................................21 
1.2.4.3 Non-Clinical Efficacy for ALLO-647 .....................................21 
1.2.5 
ALLO-501A ......................................................................................23 
1.2.5.1 Non-Clinical Safety Information for ALLO-501A .................24 
1.2.5.2 ALLO-501A Potential Risks ...................................................26 
1.2.5.3 ALLO-501A Doses Evaluated in Phase 1 of ALPHA2 ..........27 
1.2.6 
Summary of Clinical Results from the Phase 1 Portion of 
ALPHA2 ..........................................................................................................27 
1.2.6.1 Safety Observed in the Phase 1 Portion of the Study ..............28 
1.2.6.2 Efficacy Observed in the Phase 1 Portion of the Study ...........29 
1.2.6.3 ALLO-501A Phase 2 Dose ......................................................29 
1.2.6.4 RP2D for Lymphodepletion Regimen .....................................30 
1.2.7 
Biomarker Rationale ..........................................................................30 
1.2.7.1 ALLO-501A ............................................................................30 
1.2.7.2 ALLO-647 ...............................................................................31 
2. STUDY HYPOTHESIS, OBJECTIVES, AND ENDPOINTS ..........................................31 
2.1 
Study Hypothesis: ............................................................................................31 
2.2 
Objectives and Endpoints ................................................................................31 
3. STUDY DESIGN ................................................................................................................33 
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3.1 
Study Overview ...............................................................................................33 
3.2 
Test Products ....................................................................................................34 
3.3 
Study Termination ...........................................................................................35 
3.4 
Duration of Study .............................................................................................35 
4. SUBJECT ELIGIBILITY CRITERIA ................................................................................35 
4.1 
Inclusion Criteria .............................................................................................35 
4.2 
Exclusion Criteria ............................................................................................37 
4.3 
Criteria for ALLO-501A Administration (Day 0) ...........................................39 
4.4 
Contraception Requirements ............................................................................40 
4.5 
Sponsor’s Qualified Medical Personnel...........................................................41 
5. STUDY TREATMENTS ....................................................................................................41 
5.1 
Allocation to Treatment: Randomized Treatment Assignment: ......................41 
5.2 
Investigational Product Compliance ................................................................42 
5.3 
Investigational Medicinal Product Supplies ....................................................42 
5.3.1 
ALLO-501A ......................................................................................42 
5.4 
Dosage Form(s) and Packaging of ALLO-501A .............................................42 
5.4.1.1 Preparation and Dispensing of ALLO-501A ...........................42 
5.4.2 
ALLO-647 .........................................................................................42 
5.4.2.1 Dosage Form(s) and Packaging of ALLO-647 ........................43 
5.4.2.2 Preparation and Dispensing of ALLO-647 ..............................43 
5.5 
Non-Investigational Medicinal Product Supplies ............................................43 
5.5.1 
Fludarabine ........................................................................................43 
5.5.2 
Cyclophosphamide ............................................................................43 
5.6 
Administration .................................................................................................43 
5.6.1 
Fludarabine and Cyclophosphamide .................................................43 
5.6.2 
ALLO-647 .........................................................................................44 
5.6.2.1 Premedication Prior to ALLO-647 Infusion ............................44 
5.6.2.2 ALLO-647 Dose Interruption ..................................................45 
5.6.3 
ALLO-501A ......................................................................................45 
5.7 
Study Stopping Criteria....................................................................................46 
5.7.1 
Stopping Criteria for ALLO-647 .......................................................46 
5.7.2 
Stopping Criteria for ALLO-501A ....................................................46 
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5.8 
Medication Errors ............................................................................................46 
5.9 
Investigational Product Storage .......................................................................47 
5.10 
Investigational Product Accountability ............................................................47 
5.10.1 
Return or Destruction of Investigational Product Supplies ...............48 
5.11 
Concomitant Treatments ..................................................................................48 
5.12 
Toxicity Mitigation and Management .............................................................48 
5.12.1 
Cytokine Release Syndrome ..............................................................48 
5.12.1.1 Hypotension and Renal Insufficiency in the Setting of 
CRS  .................................................................................................50 
5.12.1.2 Cardiac Toxicity in the Setting of CRS ...................................50 
5.12.2 
Neurologic Toxicity ...........................................................................51 
5.12.3 
Anti-Infective Prophylaxis ................................................................51 
5.12.4 
B Cell Depletion ................................................................................53 
5.12.5 
Graft Versus Host Disease .................................................................53 
5.12.6 
Infusion-Related Reactions ...............................................................53 
5.12.7 
Blood Product Support for Anemia and Thrombocytopenia .............54 
5.12.8 
Fever and Neutropenia ......................................................................54 
5.12.9 
Hematopoietic Growth Factors ..........................................................54 
5.12.10 
Anti-Diarrheal, Anti-Emetic Therapy ...............................................54 
5.13 
Prohibited Treatments ......................................................................................55 
5.13.1 
Anti-Inflammatory Therapy ..............................................................55 
5.13.2 
Other Antitumor/Anticancer or Experimental Drugs ........................55 
5.13.3 
Viral vaccines ....................................................................................55 
6. STUDY PROCEDURES ....................................................................................................55 
6.1 
Prescreening .....................................................................................................55 
6.2 
Screening..........................................................................................................56 
6.3 
Lymphodepletion .............................................................................................56 
6.4 
Treatment .........................................................................................................57 
6.5 
Follow-up .........................................................................................................57 
6.5.1 
Follow-up for Subjects Completing Treatment .................................57 
6.5.2 
Follow-up after Randomization when subject did not receive 
study treatment .................................................................................................58 
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6.5.3 
Follow-up after Randomization and Lymphodepletion when 
subject did not receive ALLO-501A................................................................58 
6.6 
Survival Follow-up ..........................................................................................59 
6.7 
Subject Withdrawal ..........................................................................................59 
6.7.1 
Reasons for Withdrawal from Study (End of Study) ........................59 
6.7.2 
Withdrawal of consent: ......................................................................59 
6.7.3 
Lost to follow-up: ..............................................................................60 
7. ASSESSMENTS .................................................................................................................60 
7.1 
Safety Assessment ...........................................................................................61 
7.1.1 
Adverse Events ..................................................................................61 
7.1.2 
Laboratory Safety Assessment ..........................................................61 
7.1.3 
Vital Signs and Physical Examination ..............................................62 
7.1.4 
Electrocardiogram (12-Lead) ............................................................63 
7.1.5 
Echocardiogram or Multigated Acquisition Scan .............................63 
7.1.6 
Pregnancy Testing .............................................................................63 
7.2 
Tumor Response Assessment ..........................................................................64 
7.2.1 
Imaging Assessments for Independent Review Committee ..............64 
7.3 
Cell Kinetics and Pharmacokinetics Assessments ...........................................64 
7.4 
Biomarker and Pharmacodynamic Assessments .............................................65 
7.4.1 
Archival/De Novo Tumor Biopsies ...................................................66 
7.4.2 
Peripheral Blood and Derivatives ......................................................66 
7.5 
Immunogenicity ...............................................................................................66 
7.6 
Gene Expression ..............................................................................................66 
7.7 
Genomic Analyses ...........................................................................................67 
7.8 
Banked Biospecimens ......................................................................................67 
7.9 
Patient Reported Outcomes..............................................................................68 
8. ADVERSE EVENT REPORTING .....................................................................................69 
8.1 
Requirements ...................................................................................................69 
8.1.1 
Additional Details on Recording Adverse Events on the eCRF ........70 
8.1.2 
Eliciting Adverse Event Information .................................................70 
8.1.3 
Time Period for Collecting AE/AESI/SAE Information ...................70 
8.1.4 
Causality Assessment ........................................................................71 
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8.1.5 
Sponsor’s Reporting Requirements to Regulatory Authorities .........71 
8.2 
Definitions........................................................................................................71 
8.2.1 
Adverse Events ..................................................................................71 
8.2.2 
Adverse Events of Special Interest ....................................................72 
8.2.3 
Abnormal Test Findings ....................................................................73 
8.2.4 
Serious Adverse Events .....................................................................74 
8.2.5 
Hospitalization ...................................................................................74 
8.2.6 
Disease Progression as an Adverse Event .........................................75 
8.3 
Severity Assessment ........................................................................................75 
8.4 
Special Situations .............................................................................................76 
8.4.1 
Potential Cases of Drug-Induced Liver Injury ..................................76 
8.4.2 
Exposure to the Investigational Product During Pregnancy or 
Breastfeeding ...................................................................................................78 
8.5 
Data Monitoring Committee/Data Safety Monitoring Board ..........................79 
9. STATISTICAL METHODS ...............................................................................................79 
9.1 
Analysis Sets ....................................................................................................80 
9.2 
Sample Size Determination..............................................................................80 
9.3 
Statistical Methods and Properties ...................................................................82 
9.3.1 
Study Endpoints .................................................................................82 
9.3.1.1 Primary Endpoints ...................................................................82 
9.3.1.2 Secondary Efficacy Endpoints .................................................83 
9.3.2 
Efficacy Analysis ...............................................................................83 
9.3.2.1 Primary Efficacy Endpoint ......................................................83 
9.3.2.2 Analysis of Secondary Efficacy Endpoint ...............................84 
9.3.2.3 Exploratory Analysis ...............................................................85 
9.3.3 
Safety Analysis ..................................................................................85 
9.3.3.1 Adverse Events ........................................................................85 
9.3.3.2 Laboratory Test Abnormalities ................................................85 
9.3.3.3 Electrocardiogram ...................................................................85 
9.3.4 
Analysis of Pharmacokinetics and Pharmacodynamics ....................86 
9.3.4.1 ALLO-501A ............................................................................86 
9.3.4.2 ALLO-647 ...............................................................................86 
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9.3.4.3 Analysis of Pharmacodynamics ...............................................86 
9.3.5 
Randomization ...................................................................................87 
10. 
QUALITY CONTROL AND QUALITY ASSURANCE ........................................87 
11. 
DATA HANDLING AND RECORD KEEPING .....................................................88 
11.1 
Case Report Forms/Electronic Data Record ....................................................88 
11.2 
Data Management ............................................................................................88 
11.3 
Protocol Deviation ...........................................................................................88 
11.4 
Record Retention .............................................................................................89 
12. 
ETHICS .....................................................................................................................89 
12.1 
Institutional Review Board/Ethics Committee ................................................89 
12.2 
Ethical Conduct of the Study ...........................................................................89 
12.3 
Subject Information and Consent.....................................................................90 
12.4 
Reporting of Safety Issues and Serious Breaches of the Protocol or ICH 
GCP ..........................................................................................................................91 
13. 
DEFINITION OF END OF STUDY .........................................................................91 
14. 
SPONSOR DISCONTINUATION CRITERIA ........................................................91 
15. 
PUBLICATION OF STUDY RESULTS ..................................................................92 
15.1 
Communication of Results by Allogene ..........................................................92 
15.2 
Publications by Investigators ...........................................................................92 
16. 
REFERENCES ..........................................................................................................94 
APPENDIX 1 
 ABBREVIATIONS ........................................................................102 
APPENDIX 2 
 SUBJECT PERFORMANCE STATUS ECOG .............................105 
APPENDIX 3 
 ACUTE GVHD GRADING ...........................................................106 
APPENDIX 4 
 CHRONIC GVHD GRADING ......................................................107 
APPENDIX 5 
 CYTOKINE RELEASE SYNDROME MANAGEMENT ............111 
APPENDIX 6 
 MANAGEMENT OF INFUSION RELATED REACTIONS 
INCLUDING ALLERGIC REACTIONS OR ANAPHYLAXIS WITH ALLO-647 ......112 
APPENDIX 7 
 BONE MARROW RESERVE IN ADULTS .................................114 
APPENDIX 8 
 ASTCT IMMUNE EFFECTOR CELL-ASSOCIATED 
ENCEPHALOPATHY (ICE) SCORE ..............................................................................116 
APPENDIX 9 
 ASTCT ICANS CONSENSUS GRADING FOR ADULTS .........117 
APPENDIX 10 
NEUROLOGIC TOXICITY MANAGEMENT GUIDANCE .......118 
APPENDIX 11 
SUMMARY OF FOLLOW-UP ......................................................119 
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APPENDIX 12 
SCHEDULE OF ACTIVITIES .......................................................120 
SPONSOR SIGNATURE PAGE ..........................................................................................131 
INVESTIGATOR SIGNATURE PAGE ...............................................................................132 
 
 
LIST OF TABLES 
Table 1. ASTCT CRS Consensus Grading ..............................................................................49 
Table 2. Safety Laboratory Tests .............................................................................................62 
Table 3. Adverse Event Reporting ...........................................................................................69 
Table 4. Adverse Event Severity Assessment..........................................................................76 
 
LIST OF FIGURES 
Figure 1. Study Treatment .......................................................................................................15 
Figure 2. Lymphodepletion and Cell Dose ..............................................................................16 
 
Figure 4. Schema of ALLO-501A and Attributes ...................................................................24 
 
 
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OVERVIEW OF CHANGES 
An overall summary of the changes reflected in Amendment 1, dated 13 October 2022, along with the rationale for the changes, are 
provided in the following table. 
Section 
Summary of Changes 
Rationale for Change 
Synopsis; Figure 1 Schema; 
Figure 2 Lymphodepletion 
and Cell Dose; 1.2.4.3.2 
ALLO-647 Dose and 
Lymphodepletion Regimen; 
1.2.6.4 RP2D for 
Lymphodepletion Regimen; 
3.1 Study Overview 
Modified the dosing in the Fludarabine, 
Cyclophosphamide, and ALLO-647 arm to be 
FCA-90 (ALLO-647 90 mg total dose; 30 
mg/day x 3 days), and deleted the FCA-60 dose 
and ALC-based dosing requirements. 
Sponsor has determined the FCA-90 regimen to 
be optimal based on clinical response rates and 
safety tables, supported by the PK/PD data. 
Synopsis; 3.1 Study 
Overview; 5.1 Allocation to 
Treatment; 9.3.5 
Randomization;  
Changed the randomization stratification factor 
to be based on the risk factors LDH and tumor 
lesion size: 
Stratum 1:  ULN < LDH ≤ 2 x ULN and 
presence of lesion ≥5 cm 
Stratum 2:  LDH ≤ ULN or all lesions <5 cm 
The stratification factor is intended to balance 
randomized subjects across the 2 arms with less 
favorable disease characteristics of higher 
baseline LDH and bulky tumors.  
Synopsis; 2.2 Objectives 
and Endpoints 
Modified Secondary Objectives and Endpoints 
by moving ALLO-647 PK/PD and host T cells, 
and ALLO-501A cellular kinetics, and 
immunogenicity of ALLO-647 and ALLO-501A 
from Exploratory to Secondary.  
To reflect the additional components of 
investigating ALLO-647’s role in enhancing 
effectiveness of CAR T therapy. 
Synopsis; 8.5 Data Safety 
Monitoring Board; 9.2 
Sample Size Determination 
Added the DSMB’s review of SAEs for 
enrollment pausing criteria will occur after 
 have been randomized 
and had the opportunity to be followed after the 
first dose of lymphodepletion.  
Providing additional information regarding the 
DSMBs activities in monitoring safety in an 
ongoing manner throughout the study, including 
the potential to pause enrollment. 
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Section 
Summary of Changes 
Rationale for Change 
4.2 Exclusion Criteria 
The following Exclusion Criteria were modified 
or added: 
• Clarified that untreated latent tuberculosis is 
ineligible. 
• Unstable arrhythmia. 
• History of solid organ transplant (corneal transplant 
permitted). 
• History of hemophagocytic lymphohistiocytosis 
(HLH). 
• History of progressive multifocal 
leukoencephalopathy (PML). 
• Clinically significant liver disease, including viral 
or other hepatitis or cirrhosis. 
Clinically significant pulmonary disease, such as 
severe COPD; bronchospasm requiring 
intubation; interstitial lung disease, or 
pneumonitis (drug-related or autoimmune).   
These additional exclusion criteria provide further 
clarification that subjects with unstable or 
medically severe conditions, or a history of 
adverse reactions, may be unsuitable for CAR T 
therapy and are excluded.   
5.12.3 Anti-Infective 
Prophylaxis 
CMV-seropositive subjects on the FC arm may 
receive letermovir at the investigator’s 
discretion. 
 
Although CMV-seropositive subjects receiving 
the anti-CD52 antibody ALLO-647 are at the 
greater risk of CMV reactivation and should 
receive prophylaxis with letermovir, subjects 
receiving FC-alone may also be at risk, and may 
receive letermovir at the investigator’s discretion.  
7.9 Patient Reported 
Outcomes; Schedule of 
Activities 
PROs are not required to be completed before 
any other assessment during a clinic visit. 
PRO completion is aligned with visits where 
disease assessment scans are conducted.  
However, the scan results would not typically be 
available at the time the subject completes the 
PRO.  To facilitate efficient and effective clinic 
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Section 
Summary of Changes 
Rationale for Change 
visits, the PRO does not have to be completed 
before any other procedure or assessment. 
Schedule of Activities and 
Footnotes 
Removed Day 4 lymph node biopsy procedure 
A lymph node biopsy at this timepoint is not 
standard of care for lymphoma, and is removed 
from the protocol.  
Schedule of Activities and 
Footnotes 
Removed Day -5 ALLO-501A transgene level 
sample, and added Focal Copy Number Score 
sample during screening (for baseline). 
Day -5 transgene levels before CAR is not 
necessary.   
Schedule of Activities and 
Footnotes 
Removed footnote instruction to collect bone 
marrow biopy at each timepoint when tumor 
assessments are performed, as this is not 
standard of care. 
Inconsistent with standard of care, and not 
supporting study endpoints. 
9.2 Sample Size 
Determination; 9.3 
Statistical Methods  
Updates to statistical definitions or analysis 
plans as needed to support study conduct, 
including DSMB reviews. 
As needed for effective study planning. 
Throughout as applicable 
Corrected typos, formatting, section numbering, 
etc. as necessary. 
Minor corrections for consistency and accuracy 
 
 
 
 
 
 
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PROTOCOL SYNOPSIS  
Study Title: A randomized, open-label, Phase 2 study evaluating lymphodepletion with 
fludarabine (F), cyclophosphamide (C), and ALLO-647 (A) vs FC alone, in subjects with 
R/R LBCL receiving ALLO-501A allogeneic CAR T cell therapy. 
Number of Subjects: The target accrual is approximately 70 subjects, with subjects 
randomized in a 1:1 ratio to one of 2 treatment arms: lymphodepletion with FCA or FC, 
followed by ALLO-501A CAR T cell therapy.  This study is designed with an adaptive 
sample size re-adjustment.  If the criteria to adjust the sample size are met, up to 136 subjects 
may be randomized in the same 1:1 ratio. 
Test Products: 
Investigational Medicinal Products (IMPs): 
IMP1: ALLO-501A, an allogeneic CAR T targeting CD19. 
IMP2: ALLO-647 is a humanized 
 monoclonal antibody that recognizes the human 
CD52 antigen and will be used as a part of the lymphodepletion regimen.   
Non-IMPs: 
Fludarabine, cyclophosphamide, as part of the lymphodepletion regimen. 
Study Hypotheses:  ALLO-647 (A), administered with fludarabine (F) and 
cyclophosphamide (C) in a lymphodepletion regimen before ALLO-501A is efficacious in 
subjects with relapsed/refractory (R/R) large B-cell lymphoma (LBCL), as determined by 
prolongation in progression-free survival (PFS) relative to FC alone as assessed per Lugano 
Classification and Independent Review Committee (IRC). 
Study Objectives: 
Primary Objective:  To assess clinical efficacy of ALLO-647 (in a lymphodepletion regimen 
before ALLO-501A) compared to FC alone as measured by PFS and assessed by IRC in 
subjects with R/R LBCL. 
Secondary Objectives:  
• To assess the clinical efficacy of ALLO-647 as measured by ORR and assessed by 
IRC between treatment arms. 
• To assess clinical efficacy of ALLO-647 with FC (in a lymphodepletion regimen 
before ALLO-501A) compared to FC alone as measured by EFS and assessed by IRC 
in subjects with R/R LBCL. 
• To characterize the efficacy of ALLO-647 as measured by DOR and assessed by IRC 
between treatment arms. 
• To characterize other aspects of the efficacy of ALLO-647 including PFS, response 
rate per investigator review,  DOR, and overall survival. 
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• To characterize the depth and duration of lymphodepletion with and without ALLO-
647 
• To characterize the PK of ALLO-647. 
• To characterize cellular kinetics of ALLO-501A when administered with 
lymphodepletion with and without ALLO-647. 
• To characterize the pharmacodynamics of ALLO-647 on host T cells. 
• To evaluate the immunogenicity of ALLO-647 and ALLO-501A. 
• To evaluate the overall safety profile of ALLO-647 by comparing FCA 
lymphodepletion with FC lymphodepletion. 
• To evaluate the overall safety profile of ALLO-501A following lymphodepletion. 
Study Population: Key Eligibility Criteria 
Key Inclusion Criteria: 
1. Histologically confirmed diagnosis of relapsed/refractory large B cell lymphoma at last 
relapse per WHO 2017 criteria: 
a. DLBCL not otherwise specified, DLBCL coexistent with follicular lymphoma of 
any grade, EBV+ DLBCL, T cell/histiocyte rich large B cell lymphoma, DLBCL 
with IRF4/MUM1 rearrangement,  
b. High-grade B cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements,  
c. Transformation of follicular lymphoma or marginal zone lymphoma to DLBCL 
d. Primary mediastinal B cell lymphoma 
e. Follicular lymphoma Grade 3B 
2. Relapsed or refractory disease after at least 2 lines of chemotherapy including an 
anthracycline and an anti-CD20 monoclonal antibody. 
3. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1. 
4. Absence of significant donor (product)-specific anti-HLA antibodies (DSA) at screening. 
5. Adequate hematologic, renal, and liver function, including absolute lymphocyte count 
(ALC) ≥300/μL. 
6. Lactic acid dehydrogenase (LDH):  ≤2 x ULN 
Key Exclusion Criteria: 
1. Active central nervous system (CNS) involvement by malignancy.  Note: subjects with a 
history of CNS disease that has been effectively treated will be eligible. 
2. Autologous or allogeneic HSCT within last 6 months (24 weeks) prior to 
lymphodepletion. 
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3. Prior treatment with anti-CD19 targeted therapies (including CAR T cell therapy and 
bispecific antibodies, etc) will be excluded.  
4. Hypocellular bone marrow for age by institutional standard as determined from a bone 
marrow biopsy performed at time of screening. 
Study Design: 
Subjects must have relapsed or refractory LBCL after at least 2 lines of chemotherapy, 
including an anthracycline and an anti-CD20 monoclonal antibody.   
The target accrual is approximately 70 subjects, with subjects randomized in a 1:1 ratio to a 
lymphodepletion regimen of either FC or FCA.   
Randomization will be stratified based on the following risk factors: 
 
Stratum 1:  ULN < LDH ≤ 2 x ULN and presence of lesion ≥5 cm (50 mm) 
 
Stratum 2:  LDH ≤ ULN or all lesions <5 cm  
• FCA:  Lymphodepletion with FCA (n=35 subjects) 
o F 30 mg/m2 Days -5, −4, −3 
o C 300 mg/m2 Days -5, −4, −3 
o ALLO-647 30 mg/day Days -5, -4, -3 
• FC:  Lymphodepletion with FC (n=35 subjects) 
o F 30 mg/m2 Days -5, −4, −3 
o C 300 mg/m2 Days -5, −4, −3 
All subjects will be treated with ALLO-501A 120 x 106 CAR+ cells following 
lymphodepletion. 
Response assessment for study efficacy endpoints will be determined by an Independent 
Radiology Committee (IRC).  Secondary endpoints will include efficacy endpoints as 
assessed by the investigator. 
Statistical Considerations 
Sample Size Considerations 
A target of approximately 70 subjects may be randomized in the study. This study is 
designed with an adaptive sample size re-adjustment.  If the criteria to adjust the sample size 
are met, up to 136 subjects may be randomized. 
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Figure 2. Lymphodepletion and Cell Dose 
 
FCA Arm 
FC Arm 
Flu 30 
Cy 300 
ALLO-647 30 
Flu 30 
Cy 300 
 
Flu 30 
Cy 300 
ALLO-647 30 
Flu 30 
Cy 300 
 
Flu 30 
Cy 300 
ALLO-647 30 
Flu 30 
Cy 300 
 
- 
- 
- 
- 
ALLO-501A 120 
ALLO-501A 120 
Flu = Fludarabine (dose in mg/m2); Cy = Cyclophosphamide (dose in mg/m2); ALLO-647 dose in mg; 
ALLO-501A dose in ×106 CAR+ cells. 
Fludarabine dose should be adjusted based on renal function. Subjects with creatinine clearance < 80 
mL/min should receive 20 mg/m2 dose with each daily fludarabine dose or as per institutional guidelines 
(Fludarabine Drug Summary). 
 
Figure 3. Study Analysis Schema 
 
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1. INTRODUCTION 
1.1 
Mechanism of Action/Indication 
ALLO-501A is an allogeneic TRAC/CD52-knockout chimeric antigen receptor (CAR) T cell 
therapy targeting CD19. ALLO-647 is a novel human 
 monoclonal antibody (mAb) that 
recognizes the human CD52 antigen. The amino acid sequence of ALLO-647 is 
 to 
that of 
. ALLO-501A is being evaluated for the treatment of subjects with 
relapsed or refractory (R/R) large B-cell lymphoma (LBCL) and is administered after a 
lymphodepletion regimen comprising fludarabine (F), cyclophosphamide (C), and ALLO-
647 (A). 
1.2 
Background and Rationale 
CD19 is a promising target antigen for CAR T cell therapy against B cell malignancies due to 
its very restricted pattern of expression. CD19 is present on normal and malignant B cells and 
it lacks homology to other known proteins (Tedder 2009; Wang  et al, 2012). Additionally, 
virtually all B cell malignancies (with the exception of some very immature acute lymphoid 
leukemias) express CD19 on their surface (Tedder  2009). Its function is thought to be in 
establishing the threshold for B cell receptor-dependent and receptor-independent signaling, 
playing a role in modulating the balance between antigen-induced response and tolerance 
induction (Carter and Fearon, 1992). 
1.2.1 
Non-Hodgkin Lymphoma 
Non-Hodgkin lymphoma (NHL) is the most common hematological malignancy in the 
United States, with an estimated 125,850 new cases diagnosed each year (Teras et al, 2016). 
Over 60 NHL subtypes have been identified, and each subtype represents different neoplastic 
lymphoid cells (T, B, or NK cells) that have arrested at different stages of differentiation. The 
most common subtype is B cell NHL (B-NHL), which accounted for over 90% of all new 
NHL cases in 2016. 
B-NHL represents a group of different neoplasms that not only differ in pathology, but also 
in response to therapy and prognosis.  NHL can be rapidly growing (aggressive) with short 
survival, eg, diffuse large B cell lymphoma (DLBCL), or it can be slow growing (indolent). 
Despite recent therapeutic advances, more than 50% of patients with aggressive B-NHL are 
incurable.  
1.2.2 
Large B-cell Lymphoma  
LBCL, which comprises 20% to 30% of B NHLs, includes a group of molecularly diverse 
aggressive lymphomas that not only differ in their morphology, chromosomal alterations, but 
also in their signaling pathway activation and clinical outcome. The disease itself may be de 
novo or may result from transformation of indolent B lymphomas such as from transformed 
follicular lymphoma. In the US, the annual incidence rate of LBCL is 5.6 per 100,000 (SEER 
2021), and in the EU, the annual incidence rate is 3.8 per 100,000 (Tilly et al, 2015), and is 
the most common form of B-NHL. LBCL is fatal if not cured. Primary mediastinal LBCL 
and transformed follicular lymphoma are typically treated along a LBCL paradigm.   
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Approximately half of all patients with aggressive B-NHL have R/R disease, with an 
estimated 10% to 15% of patients with LBCL having primary refractory disease and an 
additional 20% to 30% relapsing after an initial objective response (Chaganti et al, 2016). 
High-grade B cell lymphomas with aberrations in MYC, BCL2, and/or BCL6, including 
“double hit” and “triple hit” lymphomas, are associated with an inferior prognosis, even in 
the newly diagnosed setting (Rosenthal and Younes, 2017). Patients with germinal center B-
cell like DLBCL experienced worse overall survival and higher relapse versus non-germinal 
center B-cell DLBCL following an autologous hematopoietic stem cell transplant (HSCT)  
(Iqbal et al, 2020).  Prognosis is poor for patients with R/R LBCL who are ineligible for 
HSCT because of age, comorbidity, or inadequate response to salvage therapy, with median 
overall survival (OS) of approximately 6 months (Crump et al, 2017). 
A meta-analysis (SCHOLAR-1 study) underscores the poor prognosis of patients with 
aggressive lymphoma that is R/R early after HSCT. In this analysis of 636 patients, the 
overall response rate (ORR) to modern salvage therapy was only 26%, complete response 
(CR) rates were 7%, and the median OS was 6.3 months (Crump et al, 2017). Patients with 
the activated B cell subtype of DLBCL, not otherwise specified, are the least responsive and 
have the worst prognosis (Lenz et al, 2008). For patients with R/R DLBCL, salvage therapies 
will lead to long-term survival in only 10% of cases. 
1.2.3 
Chimeric Antigen Receptor T cells 
Adoptive cellular immunotherapy with CAR T cells has changed the treatment landscape of 
relapsed or refractory B NHL, especially for aggressive B cell lymphomas. Clinical trials 
with anti-CD19 CAR T cell therapy have shown great activity and long-term remissions in 
high-risk, poor-prognosis DLBCL when no other effective treatment options are available 
(Chavez et al, 2019). Three autologous CAR T-cell products (lisocabtagene maraleucel 
[Breyanzi], tisagenlecleucel [Kymriah], and axicabtagene ciloleucel [Yescarta]) have 
received marketing approval (by both the US Food and Drug Administration and the 
European Medicines Agency) for the treatment of refractory DLBCL after 2 lines of therapy 
(Breyanzi USPI, Breyanzi EPAR, Kymriah USPI, Kymriah SmPC, Yescarta USPI, Yescarta 
SmPC). Others are currently being studied in the clinic. CAR T cell-related toxicity with 
cytokine release syndrome (CRS) and neurotoxicity remain important complications of this 
therapy. 
While an autologous approach has been the main focus for adoptive transfer therapies to 
date, there are a number of drawbacks to this approach. For example, the number of cells 
available for isolation from the patient may be scarce, and it is also possible that prior 
therapies or advanced age of the subject could have an impact on the cell’s functionality. The 
need to isolate, expand and transfect T cells on an individual basis will generate prolonged 
waiting periods; therefore, prevent rapid access to therapy. 
1.2.4 
Lymphodepletion Regimen Including ALLO-647 
Due to its allogeneic nature and human leukocyte antigen (HLA) mismatch, ALLO-501A is 
expected to elicit a faster endogenous CD8+ T cell-mediated host-versus-graft response than 
autologous products. As a result, ALLO-647 may be needed to produce a sufficiently deep 
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and/or durable suppression of lymphocytes, for optimal ALLO-501A expansion and 
persistence. 
Depletion of the immune cells with cytotoxic agents has been shown to enhance the 
antitumor activity of adoptive cell transfer both in mouse tumor models (Dummer et al, 
2002) and in cancer patients (Dudley et al, 2002; Childs and Barret, 2004). The mechanisms 
by which lymphodepletion enhances the anti-tumor activity have been shown to involve 
depletion of immune suppressive regulatory elements, an increase in beneficial cytokines 
such as IL-7 and IL-15, and removal of lymphocytes, which can be a sink for such cytokines 
(Gattinoni et al, 2005). These 2 cytokines, along with monocyte chemoattractant protein-1 
(MCP-1), have been shown to increase in the serum of patients following administration of 
lymphodepletion chemotherapy with fludarabine and cyclophosphamide. Patients who 
achieved remission of lymphoma developed higher serum peak levels of IL-15 and IL-10 
(Kochenderfer  et al, 2017), suggesting superior lymphodepletion was achieved. Recently, a 
multivariate analysis of the effect of lymphodepletion on the clinical outcome of autologous 
CAR T cell in a study of patients with aggressive NHL indicates that serum Day 0 MCP-1 
and peak IL-7 concentration following lymphodepletion were associated with better 
progression-free survival (PFS; Hirayama  et al, 2019), suggesting that strategies to augment 
the cytokine response to lymphodepletion are warranted.  
To increase the potential of developing a favorable cytokine profile at the time of CAR 
infusion and delay the host immune rejection of allogeneic cells, an additional anti-
lymphocyte agent (that will have minimal impact on the infused CAR T cells) is 
hypothesized to be beneficial. CD52 is a cell-surface glycoprotein present on cells that may 
lead to a host-vs-graft reaction, such as T cells, but is also present on distinct B cell 
populations, natural killer (NK) cells, monocytes, macrophages, and dendritic cells (Rao et 
al, 2012); CD52 is also dimly expressed on neutrophils (Zhao et al, 2017).  
Alemtuzumab was the first IgG1 mAb against the CD52 antigen and is known to be one of 
the most potent lymphodepleting agents (Poire et al, 2011; Morris et al, 2003). Binding of 
alemtuzumab to CD52 leads to rapid and long-lasting lymphodepletion, believed to be 
achieved through apoptosis and lysis of CD52+ immune cells via antibody-dependent cell-
mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) (Lemtrada 
USPI). Thus, the addition of an anti-CD52 mAb to the cytotoxic agents, may deepen and 
prolong the host lymphodepletion.  ALLO-647 is a novel human
 mAb that recognizes 
the human CD52 antigen. The amino acid sequence of ALLO-647 is 
 to that of 
.  Allogene is developing ALLO-647 as a lymphodepleting agent for use in 
combination with cytotoxic FC in patients prior to receiving allogeneic CD52 knockout, 
CAR T cell therapy. 
Knock-out of the CD52 gene renders ALLO-501A insensitive to anti-CD52 targeted therapy. 
As a result, ALLO-501A cells should persist in the presence of anti-CD52 mAb, while wild-
type host immune cells would be delayed in their reconstitution, allowing more time for 
tumor killing. 
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No significant direct anti-tumor activity benefit is expected from the anti-CD52 mAb. CD52 
expression is heterogeneous among aggressive B cell lymphomas with 25% of DLBCL 
demonstrating no detectable CD52 (Rodig et al, 2006).  A clinical trial studying up to 
12 weekly cycles of CAMPATH-1H with a median cumulative dose of 492 mg (range, 83 to 
2,099 mg) demonstrated only a 14% partial response (PR) rate in 50 patients with low-grade 
NHL (Lundin et al, 1998). 
This strategy of intensifying lymphodepletion in the allogeneic setting was first tested in the 
PALL and CALM studies of UCART19, a first-in-class anti-CD19 allogeneic CAR T cell 
therapy, which combined alemtuzumab with fludarabine and cyclophosphamide in pediatric 
and adult patients with R/R acute lymphocytic leukemia (ALL). Patients who received a 
lymphodepletion regimen of FC only (n=4) prior to UCART19 had no cell expansion and did 
not achieve complete molecular response (minimal residual disease negative [MRD−] CR), 
whereas 15 out of 17 patients who received alemtuzumab with the cytotoxic agents 
fludarabine and cyclophosphamide demonstrated cell expansion and 82% (14 of 17) achieved 
CR or CRi, of which 71% (10 of 14) achieved MRD− CR (Benjamin et al, 2020). These 
observations suggest that the addition of an anti-CD52 mAb improves the host 
lymphodepletion, allowing for CAR T expansion and subsequent clinical benefit.  
Inadequate lymphodepletion has also been reported with UCART22, a CD22-directed 
allogeneic CAR T cell product for the treatment of relapsed/refractory ALL, that is being 
developed by Cellectis and utilizes the same TALEN gene editing technology for CD52 
knockout as UCART19, ALLO-501 and ALLO-501A (Jain  et al, 2020).  Of note, Cellectis 
announced that alemtuzumab (an anti-CD52 mAb with same amino acid sequence as ALLO-
647) is being used as part of the lymphodepletion regimen for UCART22 in the BALLI-01 
and for UCART123 in the AMELI-01 clinical trial in R/R acute myeloid leukemia (Cellectis  
2020). Subjects (n=3) receiving alemtuzumab (with flu/cy for lymphodepletion) had 
extended host lymphocyte suppression and CAR T expansion, and subjects (n=5) who did 
not receive alemtuzumab had no expansion or response (Jain et al, 2021).   
1.2.4.1 
Fludarabine and Cyclophosphamide 
Lymphodepletion regimens containing FC form the backbone of conditioning treatment prior 
to most cell therapies including autologous CAR T therapies for hematologic malignancies 
with various doses. Fludarabine doses up to 125 mg/m2 are routinely used and 
cyclophosphamide total doses up to 1500 mg/m2 are commonly used.  Fludarabine and 
cyclophosphamide are used for conditioning before autologous CD19 CAR T therapies 
approved in the US and EU (Yescarta USPI, Yescarta SmPC, Kymriah USPI, Kymriah 
SmPC, Breyanzi USPI, Breyanzi EPAR). 
Additionally, one potential mechanism of allogeneic rejection is due to host T cells as well as 
suppressor cells resident in the lymphoma microenvironment.  Alemtuzumab has been shown 
to be effective in the vascular compartment but with limited activity in bulky lymph nodes 
(Lundin, 1998).  Allogene hypothesizes that ALLO-647 used in combination with 
cyclophosphamide would be a means to remove tissue-resident cells in the tumor 
microenvironment potentially capable of mediating rejection of allogeneic CAR T cells. 
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Therefore, to date Allogene has evaluated ALLO-647 at total doses of 39 to 90 mg 
administered with fludarabine (at a total dose of 90 mg/m2) and cyclophosphamide (at total 
doses ranging from 900 to 1500 mg/m2). 
1.2.4.2 
ALLO-647 
ALLO-647 is a novel human
 mAb that recognizes the human CD52 antigen. The amino 
acid sequence of ALLO-647 is 
 to that of 
, and ALLO-647 has shown 
similar ADCC and CDC activity in vitro and similar pharmacokinetics (PK) in a GLP 
cynomolgus monkey toxicology study. Allogene is developing ALLO-647 as a 
lymphodepleting agent for use in combination with FC in patients prior to receiving 
allogeneic CD52 knockout CAR T cell therapy. The approved dose of alemtuzumab for 
patients with multiple sclerosis is 12 mg/day for 5 days for a total of 60 mg in 1 week. The 
approved dose for patients with chronic lymphocytic leukemia is 30 mg/day three times per 
week for 12 weeks.  However, in patients with chronic lymphocytic leukemia, an inverse 
relationship exists between disease burden and PK parameters, such as Cmax and AUC 
(Campath BLA). Furthermore, the PK of alemtuzumab has been shown to be impacted by the 
starting absolute lymphocyte counts in pediatric patients undergoing allogeneic HSCT 
(Marsh et al, 2017), thus the subject-to-subject variability in host lymphocyte counts suggest 
higher doses of an anti-CD52 agent may be required.  Emerging clinical trial results across 
the allogeneic CAR T landscape have shown that, for other products, enhanced 
lymphodepletion (higher doses of flu or cy) or higher doses of CAR T cells, are required to 
avoid rejection and enable CAR T efficacy comparable to autologous CAR T therapy (Shah 
et al, 2021; CRISPR Therapeutics, 2020). 
1.2.4.2.1 
Non-Clinical Safety Information for ALLO-647 
Further details on ALLO-647 non-clinical safety may be found in the Investigator’s Brochure 
for ALLO-647. 
1.2.4.3 
Non-Clinical Efficacy for ALLO-647 
ALLO-647 was shown to bind cynomolgus monkey and human CD52 and Fc receptors and 
mediate depletion of CD52 expressing lymphocytes. The binding properties of ALLO-647 to 
neonatal Fc receptors (FcRn) and Fc-gamma receptors (FcγR) demonstrated that ALLO-647 
binding affinities were similar to the binding affinities of an isotype control human 
. 
ALLO-647 also demonstrated dose-dependent binding to human T cells. Cynomolgus 
monkey was identified as a relevant nonclinical species by binding assays conducted on 
mouse, rat, and cynomolgus monkey T and B cells that demonstrated binding of ALLO-647 
in monkey cells only. The specificity of ALLO-647 on human cells was demonstrated in a 
study of in vitro binding and CDC activity on CD52-knockout human T cells versus wild 
type T cells where binding and CDC activity was only seen on wild type T cells. To further 
demonstrate in vitro pharmacology, studies have been conducted to evaluate the ADCC and 
CDC potential of ALLO-647 and alemtuzumab and both antibodies have demonstrated 
concentration-dependent effects on human lymphocytes. For in vivo pharmacology, a single 
4-hour IV infusion of ALLO-647 in cynomolgus monkeys was administered and the 
expected tolerability, pharmacokinetics (PK), and lymphodepletion were demonstrated. 
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Taken together these studies validate ALLO-647 as an
 monoclonal anti-CD52 antibody 
capable of inducing lymphodepletion. 
Further details on ALLO-647 non-clinical efficacy may be found in the Investigator’s 
Brochure. 
1.2.4.3.1 
ALLO-647 Safety 
Similar to cytotoxic agents fludarabine and cyclophosphamide, the identified and potential 
risks for ALLO-647 consist of infusion related reactions, cytopenias, CMV 
infection/reactivation, prolonged cytopenias, infections, immunogenicity and immune 
mediated events (ALLO-647 Investigator’s Brochure).  The safety of ALLO-647 as a 
lymphodepletion agent administered with fludarabine and cyclophosphamide before ALLO-
501A CAR+ cells in Phase 1 cohorts in the ALLO-501A ALPHA2 study is described in 
Section 1.2.6.1.  
1.2.4.3.2 
ALLO-647 Dose and Lymphodepletion Regimen Selection 
In the Phase 1 portion of the ALLO-501A ALPHA2 study, before receiving ALLO-501A 
treatment, subjects were lymphodepleted with a regimen of FCA.  The following 
lymphodepletion regimens, followed by ALLO-501A, were evaluated:     
 
FCA-90 
FCA-60 
Consolidation-1 
Consolidation-2 
 
Flu 30 
Cy 300 
ALLO-647 30 
Flu 30 
Cy 300 
 
Flu 30 
Cy 300 
Flu 30 
Cy 500 
 
Flu 30 
Cy 300 
ALLO-647 30 
Flu 30 
Cy 300 
ALLO-647 30 
Flu 30 
Cy 300 
ALLO-647 30 
Flu 30 
Cy 500 
 
 
Flu 30 
Cy 300 
ALLO-647 30 
Flu 30 
Cy 300 
ALLO-647 30 
Flu 30 
Cy 300 
ALLO-647 30 
Flu 30 
Cy 500 
 
 
- 
- 
- 
ALLO-647 20 
 
- 
- 
- 
ALLO-647 20 
 
ALLO-501A 40 or 
120 
ALLO-501A 120 
ALLO-501A 120 
ALLO-501A 120 
ALLO-647 20 
 
  
- 
- 
ALLO-647 30 
ALLO-647 30 
 
 
- 
- 
ALLO-501A 120 
ALLO-501A 120 
Flu = Fludarabine (dose in mg/m2); Cy = Cyclophosphamide (dose in mg/m2); ALLO-647 dose in 
mg; ALLO-501 dose in ×106 CAR+ cells. 
The lymphodepletion regimen FCA-90 was also evaluated in the ALLO-501 ALPHA study.  
Because ALLO-501 and ALLO-501A express an identical CD19 CAR protein, target similar 
eligible large B-cell lymphoma patients, and investigate the same cell dose and 
lymphodepletion regimen in clinical trials, the data from these 2 clinical trials can be 
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analyzed together.  FCA-90 (Lymphodepletion-A) has optimal efficacy in terms of response 
(ORR and CR) and durability in LBCL CAR naïve population (Section 1.2.6.2), and 
exposure-response modeling (data on file, Allogene Inc.) supports the benefit of higher 
ALLO-647 exposure on lymphodepletion, CAR T expansion, and better clinical outcomes. 
Based on an evaluation of patient characteristics associated with safety outcomes, FCA-90 
also has an acceptable safety profile (Section 1.2.6.1) comparable to what is already 
anticipated with autologous therapy using standard doses of fludarabine and 
cyclophosphamide.   
Cytopenias are frequent with autologous CAR T cell therapies and have increasingly been 
seen to be relatively prolonged, including patients with marrow aplasia/hypoplasia lasting 
several weeks up to months following CAR T cell infusion and requiring stem cell 
transplants (Jain et al, 2020; Strati  et al, 2021; Nahas et al, 2020).  Lymphodepletion (and 
more specifically T cell depletion) is essential for CAR T activity and clinical benefit.  
However, controlling and reducing the rate of prolonged cytopenias is important to prevent 
serious and life-threatening infections.   
Medical review and individual case evaluations of subjects who developed prolonged 
cytopenias across dose cohorts in the ALLO-501A/ALLO-501 program suggests that there 
are inherent risk factors for developing prolonged cytopenias.  These factors include prior 
autologous CAR T, recent autologous or allogenic HSCT (within 6 months), hypocellular 
bone marrow at screening, and lower ALC counts.   
In the current study protocol, the risk factors for prior autologous CAR T, recent autologous 
HSCT, and hypocellular bone marrow at screening are addressed in the protocol eligibility 
criteria.   
Based on the Phase 1 experience, in Phase 2 subjects will be treated with ALLO-501A 120 x 
106 CAR+ cells following lymphodepletion with FCA-90 for subjects randomized to the FCA 
arm: 
• F 30 mg/m2 Days -5, −4, −3 
• C 300 mg/m2 Days -5, −4, −3 
• ALLO-647 30 mg/day Days -5, -4, -3 
Subjects randomized to the FC arm (without ALLO-647) will receive: 
• F 30 mg/m2 Days -5, −4, −3 
• C 300 mg/m2 Days -5, −4, −3 
1.2.5 
ALLO-501A 
ALLO-501A is engineered using a self-inactivating lentiviral vector (LVV), which drives 
expression of a second-generation CAR, thus redirecting T cells to target CD19. The CAR 
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construct utilized in ALLO-501A combines a single-chain variable fragment (scFv) derived 
from a murine anti-human CD19 monoclonal antibody, with the human CD8 hinge and 
transmembrane domains, and a cytoplasmic tail composed of human 4-1BB co-stimulatory 
and human CD3ζ signaling domains. 
ALLO-501A was additionally engineered using TALEN® gene editing technology. TALEN® 
are artificially engineered nucleases that are capable of generating site-specific double-strand 
DNA breaks at a desired target site leading to inactivation of the targeted gene. ALLO-501A 
is generated by transfection of two pairs of TALEN mRNA: one pair to inactivate TRAC and 
one pair to inactive CD52 (Figure 4). 
The inactivation of CD52 leads to the loss of CD52 surface expression, allowing use of 
ALLO-501A in the presence of anti-CD52 depleting antibodies such as ALLO-647. 
The inactivation of TRAC, which encodes the T cell receptor constant region, results in the 
elimination of a functional TCRα/β complex on the cell surface, thus circumventing the 
recognition of MHC disparities between donor and recipient through the donor cell’s TCR 
and preventing the potential development of graft-versus-host disease (GvHD). 
Figure 4. Schema of ALLO-501A and Attributes 
 
ALLO-501A is a pre-manufactured, TCRαβ depleted T cell suspension designed to become 
active, proliferate, secrete cytokines and kill CD19+ B cells following administration to 
lymphodepleted subjects with relapsed/refractory LBCL.  
Further details on ALLO-501A may be found in the Investigator’s Brochure. 
1.2.5.1 
Non-Clinical Safety Information for ALLO-501A 
A risk-based approach was followed to address the potential safety concerns connected with 
the use of ALLO-501A. The following risks have been identified. 
1. Risk of off-target toxicity related to the CD19 CAR of ALLO-501: 
The specificity of the ALLO-501A scFv to its intended target antigen CD19 was 
demonstrated in a good laboratory practice (GLP) tissue cross-reactivity study. Specific 
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staining was observed in the normal B cell compartment whereas no unexpected off-
target binding was observed in any other cell type of the 37 human tissues examined. 
2. Risk of GvHD related to the allogeneic nature of ALLO-501A: 
Residual TCRα+ T cells are depleted from ALLO-501A preparations after TALEN 
inactivation of TRAC and prior to cryopreservation, to minimize the number of TCRα+ 
T cells a subject may receive. Furthermore, an in vivo study demonstrated that TCRαβ–
_CD52+/–_T cells did not induce GvHD in an immunocompromised mouse model (Poirot  
et al, 2015). 
3. Risks of tumorigenicity related to:  
The use of a lentiviral vector: 
The risk of tumorigenicity is mitigated by the use of self-inactivating lentiviral 
vectors to prevent the transactivation of unwanted genes. As of today, no severe AEs 
have been observed in previous clinical experiences with such self-inactivating 
vectors (Cartier et al, 2009; Zhou et al, 2010; Biffi et al, 2011; Scaramuzza et al, 
2013). Furthermore, the number of integrated lentiviral vectors per cell is controlled 
to minimize the risk of insertional mutagenesis. 
The use of TALEN-mediated gene editing: 
The risks of TALEN off-target editing and chromosomal translocations were assessed 
by high throughput sequencing of predicted off-target sites, whole genome 
sequencing (WGS), karyotype analysis, fluorescence in situ hybridization (FISH), and 
in vitro aberrant proliferation assays. To mitigate these potential risks the TRAC and 
CD52 TALEN are introduced into the cells during the production process by 
electroporation of mRNA, thus resulting in only transient expression of the nucleases. 
In vitro experiments showed that: 
• No significant mutagenesis was identified at the top 15 predicted TRAC and CD52 
TALEN off-target sites in TALEN-transfected cells compared to control cells. Also, 
WGS revealed a similar number of variants in TALEN -edited and control samples, 
suggesting that the background is consistent (ie, detection of single-nucleotide 
polymorphisms [SNPs] and insertions/deletions [INDELs] was similar between all 
samples) and TALEN are not inducing mutations at a globally detectable rate in 
T cells; 
• Karyotype, FISH, WGS, and PCR assays confirmed the presence of TRAC:CD52 
translocations (ie, translocations involving the 2 chromosomes simultaneously 
targeted by the 2 TALEN). The TRAC:CD52 translocations, however, showed no 
significant increase following a 4,000-fold expansion in culture, suggesting TALEN 
gene-edited T cells do not acquire any proliferative advantage. 
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Risk of generating replication-competent lentivirus (RCL): 
The lentiviral vector used to generate ALLO-501A is derived from HIV-1 and there is a 
theoretical risk that random recombination unintentionally reconstitutes a replication-
competent and potentially pathogenic virus. The potential for generating RCL is mitigated 
through the use of a third-generation vector, in which all sequences that encode lentiviral 
proteins have been deleted from the transfer vector. Furthermore, the HIV-1 proteins tat and 
env, plus nef, vif, vpr, and vpu, all of which are essential for HIV-1 pathogenesis and 
replication in vivo, are not expressed during production of the lentiviral vector particles. RCL 
absence is part of the release criteria for all ALLO-501A Good Manufacturing Practice 
(GMP) batches. 
1.2.5.2 
ALLO-501A Potential Risks 
The safety risks potentially associated with the administration of ALLO-501A are those 
expected from the lymphodepletion regimen, and those described for anti-CD19 autologous 
CAR T cell drug products (Breyanzi USPI and SmPC; Kymriah USPI and SmPC; Yescarta 
USPI and SmPC), and the allogenic CARs UCART19 and ALLO-501. They comprise CRS, 
neurotoxicity, infections, prolonged cytopenia, infusion-related reaction, 
hypogammaglobulinemia, acute and chronic GVHD, and genotoxicity/tumorigenicity. Tumor 
lysis syndrome (TLS) is a potential risk due to the underlying disease. Toxicity grading and 
management are provided in Section 8. 
Refer to ALLO-501A IB for additional information on the potential risks. 
CRS is common to anticancer immunotherapies (adoptive T-cell therapies and bispecific 
antibodies, eg, blinatumomab) and associated with elevated levels of inflammatory 
cytokines. The presentation of CRS can vary, and clinical signs and symptoms may include 
constitutional (fever, rigors, headaches, malaise, fatigue, arthralgia), vascular (hypotension), 
respiratory (hypoxia, dyspnea) cardiac (tachycardia), gastrointestinal (nausea, and vomiting), 
laboratory (coagulation, renal, and hepatic), skin (rash) and neurological (aphasia, altered 
level of consciousness). Treatment with supportive care, tocilizumab, or tocilizumab and 
corticosteroids should be used as indicated at the first sign of CRS symptoms. The severity of 
CRS will be assessed according to the American Society for Transplantation and Cellular 
Therapy 2019 (Lee et al, 2019) grading criteria. 
Neurological toxicities including severe or life-threatening reactions occurred in 60% and 
81% of the subjects with R/R DLBCL following treatment with Kymriah and Yescarta, 
including Grade ≥3 in 19% and 26% of subjects, respectively (Kymriah USPI 06/2021; 
Yescarta USPI 04/2021). The onset of neurological toxicity can be concurrent with CRS, 
following resolution of CRS or in the absence of CRS. The most common neurological 
toxicities observed with Kymriah and Yescarta include headache (21% and 44%), 
encephalopathy (34% and 57%), delirium (6% and 17%), anxiety (9% and 9%), sleep 
disorders (9%), dizziness (11% and 21%), tremor (7% and 31%). Other manifestations 
included peripheral neuropathy, leukoencephalopathy, seizures, cerebral edema, mutism, and 
aphasia. 
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Due to the lymphodepletion prior to ALLO-501A infusion, all subjects are expected to 
experience a long-lasting lymphocyte count decrease and are at risk for prolonged cytopenias 
and infections. Study inclusion criteria are in place to reduce the risk for prolonged 
cytopenias; subjects will be screened and monitored for endemic infections and will be 
required to receive anti-infective prophylaxis as recommended by the US National 
Comprehensive Cancer Network for subjects receiving alemtuzumab (NCCN Guidelines, 
2021; Section 5.12.3). 
It is possible that B cell depletion and hypogammaglobulinemia will occur due to the effects 
of ALLO-501A on normal B cells. Gamma globulin may be administered for 
hypogammaglobulinemia according to institutional guidelines. 
Acute GvHD cannot be completely excluded despite the depletion of TCRα/β expressing 
T cells in ALLO-501A manufacturing. Risk of chronic GvHD is mitigated by host immune 
recovery at a distance from lymphodepletion, and rejection of allogenic cells consequently. 
The risk of chronic GvHD will be monitored during the study and in long term follow-up 
(LTFU) studies. Institutional guidelines for the treatment of acute and chronic GvHD will 
apply. 
Genotoxicity and tumorigenicity of ALLO-501A are inherent risks with gene editing through 
insertional mutagenesis with lentiviral transduction, and off-target gene deletion and/or 
chromosomal translocation after TALEN®. The risk of insertional mutagenesis is mitigated 
by the use of a nonreplicative self-inactivating LVV. 
1.2.5.3 
ALLO-501A Doses Evaluated in Phase 1 of ALPHA2 
In Phase 1 of ALPHA2, the ALLO-501A cell doses that were evaluated were 40 x 106 (n=1 
subject) and 120 x 106 CAR+ cells and Consolidation which entailed 2 dose doses of ALLO-
501A dosed 28 days apart. The consolidation dose used 120 x 106 CAR+ cells per dose.  The 
single cell dose of 120 x 106 CAR+ cells was selected as the RP2D to be used in Phase 2 
(Section 1.2.6.3). 
1.2.6 
Summary of Clinical Results from the Phase 1 Portion of ALPHA2 
In the Phase 1 portion of ALPHA2 as of 18 Oct 2021, 29 subjects have enrolled and 28 have 
been evaluated.   
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Lymphodepletion Regimen (with ALLO-501A on 
) 
Enrolled Treated 
FCA-60: F 30 mg/m2/day, C 300 mg/m2/day, and A 30 mg/day on 
 
 and ALLO-501A 120 x 106  at 
 
2 
2 
FCA-90: F 30 mg/m2/day, C 300 mg/m2/day, and A 30 mg/day on 
, 
; one patient at ALLO-501A 40 x 106 and 4 at ALLO-501A 120 x 
106 at 
 
5 
5 
Consolidation 1:  F 30 mg/m2/day, C 300 mg/m2/day, and A 30 mg/day on 
, and ALLO-501A 120 x 106 at 
 plus ALLO-647 30 mg 
on 
 and ALLO-501A 120 x 106 on 
 (if eligible)  
12 
11 
Consolidation 2:  F 30 mg/m2/day, C 500 mg/m2/day, and A 20 mg/day on 
 and ALLO-501A 120 at 
 plus ALLO-647 30 mg on 
 and ALLO-501A 120 x 106 on 
 (if eligible)  
10 
10 
 
One subject in FCA-90 was enrolled and completed lymphodepletion but experienced new 
onset CNS relapse and did not receive ALLO-501A. In Consolidation-1 one subject was 
withdrawn from the study due to COVID-19 infection prior to the start of lymphodepletion.  
No dose-limiting toxicities (DLTs) related to ALLO-647 or ALLO-501A were observed.   
1.2.6.1 
Safety Observed in the Phase 1 Portion of the Study 
In a preliminary analysis of ALLO-501A-201 ALPHA2 Phase 1 data (Lekakis  et al, 2021) 
among a total of 28 subjects evaluable for safety across the lymphodepletion regimen and 
dose levels of ALLO-501A, as of 18 Oct 2021 data cutoff, no DLTs attributed to ALLO-647 
or ALLO-501A were observed.  The reported safety events for ALLO-647 and ALLO-501A 
were manageable.  Cytopenias were the most common AEs occurring in ≥30% of subjects 
regardless of relationship; neutropenia 57.1% (16/28), anemia, and thrombocytopenia 46.4% 
each (13/28) and white blood cell count decreased 35.7% (10/28). Similarly, the most 
common (≥25%) Grade ≥3 events were neutropenia 57.1% (16/28), thrombocytopenia 35.7% 
(10/28), anemia and white blood cell count decreased 32.1% each (9/28), and lymphopenia 
28.6% (8/28). There were three subjects who experienced prolonged cytopenias, two of 
which were with the Consolidation-2 regimen where Cy 500 mg/m2/day was explored as part of 
the lymphodepletion regimen.  CRS of any grade was observed in 10.7% (3/28) of subjects, all 
ASTCT Grade 1 or 2, which resolved with standard treatment.  Neurologic toxicity was 
reported in 21.4% (6/28) of subjects, including 1 Grade 2 ICANS.  No events of GvHD (any 
grade) were observed. Infusion-related reactions, all Grade 1 or 2, were observed in 25% 
(7/28) of treated subjects,  and no subject required dose reduction due to infusion-related 
reactions. Infection of any grade was observed in 35.7% (10/28), with the most common 
infections being viral infections (25.0%, 7/28).  Two (7.1%) subjects had Grade 3 infections:  
1 subject experienced Grade 3 CMV reactivation (FCA-60 regimen), and 1 subject 
experienced Grade 3 HHV-6 reactivation, bacterial sepsis, and fungaemia (Consolidation-2).  
Ten (35.7%) subjects experienced SAEs.  Three (10.7%) subjects experienced SAEs related 
to ALLO-647:  CMV reactivation, HHV-6 reactivation, and vomiting; and 4 (14.8%) 
subjects experienced SAEs related to ALLO-501A:  aplastic anemia; bacterial sepsis; 
cytogenetic abnormality; fungaemia; ICANS Grade 2; CRS, pyrexia; and vomiting.   
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There was a finding of new chromosomal structural variant in donor derived T cells in a 
subject who was undergoing a bone marrow assessment as part of a workup for aplastic 
anemia (chromosome 14 inversion). Investigation concluded that the chromosomal 
abnormality was unrelated to transcription activator-like effector nucleases (TALEN)® gene 
editing or to Allogene’s manufacturing process and was of no clinical significance. No other 
gross chromosomal abnormalities were noted, and the cell morphologic appearance, 
immunophenotype, clinical behavior of the cells, and localization were not suggestive of 
leukemia. Sequencing of the inversion junctions showed that the inversion sites were not 
associated with on-target or off-target TALEN activity but were sites of V(D)J 
recombination. Similar structural variants have been detected in post-thymic, mature T cells 
of normal individuals and are believed to be consequences of V(D)J recombination during 
normal T cell development (Callén et al 2009, Machado et al, 2021) and unrelated to TALEN 
gene editing.   
The safety profile of the FCA-90 (n=5) lymphodepletion regimen in ALPHA2, although 
small numbers, was generally comparable with the other lymphodepletion regimens 
evaluated in Phase 1.  There were no ALLO-647-related SAEs with FCA-90.  There were no 
events of prolonged cytopenia, and although all 5 subjects experienced an infection, they 
were similar in type (CMV reactivation; HHV-6 reactivation) and of the same or lesser 
severity (Grade 1 or 2) as reported in other lymphodepletion regimen cohorts in the study.   
1.2.6.2 
Efficacy Observed in the Phase 1 Portion of the Study 
In the ALPHA2 study, an ORR of 50% and a CR rate of 27.3% was observed in CAR T 
naïve subjects with R/R LBCL as of 18 Oct 2021.  In the ALLO-501 ALPHA study (CD19 
allogeneic CAR T), the same population had an ORR of 64%, with 43% CR rate (Neelapu et 
al, 2021).    
In CAR-naïve LBCL subjects in FCA-90 lymphodepletion cohorts, in the ALPHA2 study 
there was 1 responder (CR) of 2 evaluable subjects, and in ALPHA, the ORR was 67%, with 
a CR rate of 67% (data cutoff 18 Oct 2021; data on file, Allogene).   
1.2.6.3 
ALLO-501A Phase 2 Dose 
For the ALLO-647-201 study, to arrive at the ALLO-501A cell dose and the RP2D 
encompassing both the lymphodepletion regimen and the ALLO-501A dose, the totality of 
data from ALLO-501A, ALLO-501 and ALLO-647 were considered.   
Across the ALPHA and ALPHA2 studies, allogeneic anti-CD19 CAR T cells were evaluated 
at cell doses of 40 x 106, 120 x 106, and 360 x 106.  A manageable safety profile was 
observed across all cell doses evaluated with no DLT or GvHD observed (Neelapu et al, 
2020).  Anti-tumor activity was observed across all cell dose levels, and cell expansion was 
not markedly different between the 120 x 106 and 360 x 106 dose levels (Neelapu et al, 
2020).  Given this, and the manageable safety profile across all cell dose levels, the 120 x 106 
cell dose level was selected as the RP2D for the ALPHA2 Phase 2 study. 
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1.2.6.4 
RP2D for Lymphodepletion Regimen 
Cohorts across the ALPHA and ALPHA2 studies were evaluated for selection of the RP2D 
encompassing both the cell dose and the lymphodepletion regimen.  Among these cohorts, 8 
subjects previously untreated with CD19 targeted CAR T cells were treated with the FCA-90 
lymphodepletion regimen and a minimum cell dose of 120 x 106.  This regimen demonstrated 
a response and CR rate of 62.5%, superior to other cohorts.  Additionally, data indicate that 
50% (4/8) of subjects in this group remain in ongoing complete remission, relative to 
ongoing complete remission rates of 0% to 30% in other dose cohorts. In addition, as 
durability data has matured, among subjects with the opportunity to be followed for 6 
months, duration of response from this group is clinically meaningful (follow-up range from 
17 to 24 months).  Finally, Allogene’s exposure-response analysis have shown that higher 
ALLO-647 exposure is associated with increased depth and duration of host T cell depletion, 
increased CAR T expansion, and higher rates of clinical response. Therefore, based on 
comparison of response rates and exposure-response modelling, Allogene considers the 
FCA-90 preferable to both FCA-60 regimen and the consolidation regimens previously 
tested. 
1.2.7 
Biomarker Rationale 
1.2.7.1 
ALLO-501A 
The objectives of the biomarker assessments will be to understand the relationship between 
the cellular kinetics, phenotype, and pharmacodynamic activity of ALLO-501A, in relation to 
its anti-tumor activity and safety profile. This understanding may identify a phenotypic 
profile that optimizes anti-tumor activity while minimizing the risk of toxicity. In support of 
these efforts, various cellular, molecular and protein-based assays may be deployed such as 
multiparametric flow cytometry, qPCR, single cell RNA-seq, ELISA, IHC etc. 
The cellular kinetics of ALLO-501A may be measured using multiparametric flow 
cytometry, and/or PCR-based molecular assays, to elucidate transgene levels, allowing for 
both the precise quantitation of CAR+ T cells, as well as immunoprofiling of the CAR T 
drug product at baseline and over the course of the study. The relative proportion of naïve, 
memory, activated and exhausted CAR+ T cells may be monitored and correlated with both 
the quantity and duration of the CAR T cells and any observed anti-tumor and/or safety 
response. The absence of risk of replication competent lentivirus (RCL) may be monitored, 
eg, PCR-based assay, for any relationship to safety and/or efficacy endpoints.  
A second imperative of the biomarker plan will be to understand how ALLO-501A CAR 
T cell drug product behaves in the context of the lymphodepletion regimen comprising of 
fludarabine, cyclophosphamide, and ALLO-647 and how it interacts with the recipient’s 
immune cells as they re-populate. The re-population of endogenous immune cells may be 
monitored by TBNK assays and multiparametric flow cytometry. Subjects’ samples may be 
submitted to high resolution HLA typing (locally or centrally) to understand the influence of 
differing degrees of HLA mismatch between the recipient and the donor cell populations. 
Immunogenicity to the CAR T cell population may be monitored by measurement of 
anti-CAR (scFv), anti-TALEN antibodies and anti-donor HLA antibodies. Finally, the 
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proportion of CAR T cells that express TCR may be measured to monitor for TCR driven 
clonal expansion and the risk of GvHD. 
 
 
 
 
 
 
 
 
1.2.7.2 
ALLO-647 
The goal of the lymphodepletion strategy is to deplete endogenous lymphocytes to a 
sufficient depth and duration to permit maximal expansion of allogeneic CAR T cells, 
leading to clinical response. The efficacy of ALLO-647 as a lymphodepletion agent will be 
assessed through measures of the depth and duration of host lymphocyte depletion. The depth 
and duration of lymphodepletion in peripheral blood will be quantitatively measured using 
local ALC assays for the baseline assessment and a central lab-based flow cytometric assay 
to detect T, B, and NK cell populations at specified timepoints, noted in the Schedule of 
Activities. Additionally, exposure of ALLO-647 in serum will be monitored using an 
immunoassay specific for ALLO-647. Finally, protein expression of CD52, the target of 
ALLO-647, may be monitored in peripheral blood samples, eg, using flow cytometric 
analysis, and/or in lymph node biopsies, eg, using immunohistochemical analysis. The 
collection of biomarker samples is described in the Schedule of Activities and the study 
laboratory manual. 
2. STUDY HYPOTHESIS, OBJECTIVES, AND ENDPOINTS 
2.1 
Study Hypothesis: 
ALLO-647 (A), administered with fludarabine (F) and cyclophosphamide (C) in a 
lymphodepletion regimen before ALLO-501A is efficacious in subjects with 
relapsed/refractory (R/R) LBCL, as determined by prolongation in progression-free survival 
(PFS) relative to FC alone as assessed per Lugano Classification and Independent Review 
Committee (IRC). 
2.2 
Objectives and Endpoints 
Primary Objectives: 
Primary Endpoints: 
Efficacy  
• To assess clinical efficacy of ALLO-647 (in a 
lymphodepletion regimen before ALLO-501A) 
compared to FC alone as measured by PFS and 
assessed by IRC in subjects with R/R LBCL. 
Efficacy  
• PFS in FCA vs FC alone, defined as the time from 
randomization to disease progression, or relapse 
per the Lugano classification criteria (Cheson  et al, 
2014) as assessed by IRC or death 
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Secondary Objectives: 
Secondary Endpoints: 
Efficacy 
• To assess the clinical efficacy of ALLO-647 as 
measured by ORR and assessed by IRC. 
• To assess clinical efficacy of ALLO-647 with FC 
(in a lymphodepletion regimen before ALLO-
501A) compared to FC alone as measured by EFS 
and assessed by IRC in subjects with R/R LBCL. 
• To characterize the efficacy of ALLO-647 as 
measured by DOR and assessed by IRC 
• To characterize other aspects of the efficacy of 
ALLO-647, including PFS, response rate per 
investigator review, DOR, and overall survival 
• To characterize the depth and duration of 
lymphodepletion with and without ALLO-647 
Efficacy 
• ORR in FCA vs FC alone, defined as assessment of 
CR or PR, assessed using the Lugano classification 
criteria 2014; Cheson , et al, 2014) by IRC at any 
time up through commencement of new anti-cancer 
therapy or withdrawal of consent. 
• EFS in FCA vs FC alone, defined as the time from 
randomization to disease progression or relapse per 
the Lugano classification criteria 2014 as assessed 
by IRC and per investigator assessment, new anti-
cancer therapy, or death 
• DOR, defined as time from the first observed 
response to disease progression or relapse (per IRC 
and per investigator assessment) or death 
• ORR in FCA vs FC alone per investigator 
assessment at any time up through commencement 
of new anti-cancer therapy or withdrawal of 
consent 
• Best overall response (CR, PR, SD, PD) (per IRC 
and per investigator assessment) at any time up 
through commencement of new anti-cancer therapy 
or withdrawal of consent 
• PFS in FCA vs FC alone, defined as time from the 
randomization to progression or relapse per 
investigator assessment per the Lugano 
classification criteria as assessed by investigator, or 
death 
• TTR, defined as the time from randomization to the 
first observed response (per IRC and per 
investigator assessment) 
• OS in FCA vs FC alone, defined as the time from 
randomization to death 
• Depth and duration of lymphodepletion, as 
assessed by lymphocyte count 
• To characterize the PK of ALLO-647 
• PK concentrations will be used in a population PK 
model 
• To characterize cellular kinetics of ALLO-501A 
when administered with and without ALLO-647 
• ALLO-501A expansion and persistence, eg, Cmax 
and AUC. 
• To characterize the pharmacodynamics of ALLO-
647 
• Pharmacodynamics will be evaluated on host T cell 
counts 
• To evaluate immunogenicity of ALLO-501A and 
of ALLO-647 
• The incidence of ADA against ALLO-501A scFv 
and/or TALEN® 
• The incidence of ADA against ALLO-647 
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Safety 
• To evaluate the overall safety profile of ALLO-647 
by comparing FCA lymphodepletion with FC 
lymphodepletion 
• To evaluate the overall safety profile of ALLO-
501A following lymphodepletion 
Safety 
• AEs as characterized by preferred term, frequency, 
severity, timing, seriousness, and relationship to 
ALLO-647, and by FCA vs FC 
• The incidence of infusion-related reactions, 
cytopenias, and infections 
• AEs as characterized by preferred term, frequency, 
severity timing, seriousness, and relationship to 
ALLO-501A and by FCA vs FC 
• The incidence and severity of CRS, 
neurotoxicity, infections, hematologic toxicities, 
prolonged cytopenias, and GVHD 
• The incidence and severity of clinically significant 
laboratory toxicities. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
  
 
 
  
ADA = anti-drug antibody; AE = adverse event; CR = complete response; CRS = cytokine release syndrome; 
DOR = duration of response; EFS = event-free survival; 
 
 FC = fludarabine and cyclophosphamide; FCA = fludarabine, cyclophosphamide, and ALLO-647; GVHD 
= acute graft-vs-host disease; IRC = independent review committee; LBCL = large B-cell lymphoma; MRD = 
minimal residual disease; ORR = overall response rate; OS = overall survival; PK = pharmacokinetic(s); PD = 
progressive disease; PR = partial response; 
; PFS = progression-free survival; 
;  R/R = relapsed/refractory; SD = stable disease; 
; 
TTR = time-to-response 
3. STUDY DESIGN 
3.1 
Study Overview 
This is a randomized, open-label, multicenter Phase 2 study evaluating the safety, and 
efficacy of lymphodepletion with fludarabine (F), cyclophosphamide (C), and ALLO-647 
(A) vs FC alone, in subjects with R/R LBCL receiving ALLO-501A allogeneic CAR T cell 
therapy. 
The study treatment schema is shown in Figure 1, the lymphodepletion and cell dose is in 
Figure 2 and the study evaluation plan is shown in Figure 3. For an individual subject, the 
study will be divided into different periods including pre-screening (optional), screening, 
lymphodepletion, treatment, and follow up (Figure 1).   
Subjects must have relapsed or refractory disease after at least 2 lines of chemotherapy, 
including an anthracycline and an anti-CD20 monoclonal antibody.   
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The target accrual is approximately 70 subjects, with subjects to randomized in a 1:1 ratio to 
one of 2 treatment arms: 
• FCA:  Lymphodepletion with FCA (n=35 subjects). 
o F 30 mg/m2 Days -5, −4, −3 
o C 300 mg/m2 Days -5, −4, −3 
o ALLO-647 30 mg/day Days -5, -4, -3  
• FC:  Lymphodepletion with FC (n=35 subjects) 
o F 30 mg/m2 Days -5, −4, −3 
o C 300 mg/m2 Days -5, −4, −3 
All subjects will be treated with ALLO-501A 120 x 106 CAR+ cells following 
lymphodepletion. 
Treatment randomization will occur centrally.  Subjects will be assigned randomly in a 1:1 
ratio to a lymphodepletion regimen of either FC or FCA.   
Randomization will be stratified based on the following risk factors: 
 
Stratum 1:  ULN < LDH ≤ 2 x ULN and presence of lesion ≥5 cm (50 mm) 
 
Stratum 2:  LDH ≤ ULN or all lesions <5 cm  
Response assessment for study efficacy endpoints will be determined by an Independent 
Radiology Committee (IRC).   
This study is designed with an adaptive sample size re-adjustment.  If the criteria to adjust the 
sample size are met, up to 136 subjects may be randomized in the same 1:1 ratio. 
3.2 
Test Products 
Investigational Medicinal Products (IMPs): 
IMP1: ALLO-501A, an allogeneic CAR T targeting CD19. 
IMP2: ALLO-647 is a humanized 
 monoclonal antibody that recognizes the human 
CD52 antigen and will be used as a part of the lymphodepletion regimen.   
Non-IMPs: 
Fludarabine; cyclophosphamide.  as part of the lymphodepletion regimen.   
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3.3 
Study Termination  
The study will end when all subjects treated with ALLO-501A have been followed for at 
least 
 from randomization, have withdrawn consent for any further contact, been 
lost to follow-up, or died, unless the study is terminated by the sponsor earlier. 
3.4 
Duration of Study 
The estimated accrual for the study is approximately 24 months. These patients will be 
followed for 
 from randomization. The overall duration of the study is expected to 
be approximately 84 months from first subject randomized to last subject last visit. 
Subjects will participate in the study for approximately
 and will subsequently roll-
over to a long-term follow up study for an extended safety monitoring period. 
4. SUBJECT ELIGIBILITY CRITERIA 
This study can fulfill its objectives only if appropriate subjects are enrolled/randomized. The 
following eligibility criteria are designed to select subjects for whom participation in the 
study is considered appropriate. All relevant medical and nonmedical conditions should be 
taken into consideration when deciding whether a particular subject is suitable for this 
protocol. Sponsor may request the review of selected screening assessments prior to 
randomization. 
4.1 
Inclusion Criteria 
Subjects must meet all the following inclusion criteria to be eligible for randomization in the 
study.  Eligibility based on disease characteristics will be determined locally (by 
investigator/site personnel).  
1. Histologically confirmed diagnosis of relapsed/refractory large B-cell lymphoma at last 
relapse per WHO 2017: 
a. DLBCL not otherwise specified, DLBCL coexistent with follicular lymphoma of 
any grade, EBV+ DLBCL, T cell/histiocyte rich large B cell lymphoma, DLBCL 
with IRF4/MUM1 rearrangement,  
b. High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements,  
c. Transformation of follicular lymphoma or marginal zone lymphoma to DLBCL 
d. Primary mediastinal B cell lymphoma 
e. Follicular lymphoma Grade 3B 
2. At least 1 measurable lesion at time of randomization according to the revised IWG 
Response Criteria for Malignant Lymphoma (Cheson et al, 2014) 
a. A measurable node must have a longest transverse diameter greater than 1.5 cm 
b. A measurable extranodal lesion must have a longest diameter greater than 1.0 cm 
3. Relapsed or refractory disease after at least 2 lines of chemotherapy including an 
anthracycline and an anti-CD20 monoclonal antibody.  
4. Male or female subjects ≥18 years of age. 
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5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1. 
6. Absence of donor (product)-specific anti-HLA antibodies (DSA) at screening. 
7. Adequate hematological function, including: 
a. Absolute neutrophil count (ANC) ≥1,000/µL (without growth factor support in the 
previous 7 days with filgrastim or 14 days with pegfilgrastim prior to screening). 
b. Platelet count ≥50,000/µL (without transfusion support during the previous 7 days 
prior to screening) 
c. Hemoglobin ≥8 g/dL (≥5 mmol/L) 
d. Absolute lymphocyte count (ALC) ≥300/μL 
8. Adequate Renal Function:  estimated creatinine clearance ≥50 mL/min (Cockcroft-Gault) 
or directly measured with 24-hour urine collection. 
9. Adequate Liver Function, including: 
a. Total bilirubin ≤1.5 × ULN, except in subjects with Gilbert’s Syndrome who must 
have a total bilirubin ≤3 × ULN; 
b. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3 × ULN; 
≤5.0 × ULN if there is liver involvement by the tumor; 
c. Alkaline phosphatase ≤2.5 × ULN (≤5 × ULN in case of bone metastasis). 
10. Lactic acid dehydrogenase (LDH):  ≤2 x ULN 
11. Normal blood oxygen saturation level (SpO2) >92% on room air. 
12. Left ventricular ejection fraction (LVEF) ≥40% and no clinically significant cardiac-
related pericardial or pleural effusion at screening. 
13. Resolved acute effects of any prior therapy to baseline severity or CTCAE Grade ≤1 
except for adverse events (AEs) not constituting a safety risk by investigator judgement. 
14. Negative for hepatitis B antigen. (Subjects who are HBs Ag and/or Anti-HBc positive are 
not eligible. If indeterminate results are obtained, viral DNA levels should be measured 
to confirm negative viral status). 
15. Seronegative for hepatitis C antibody. If hepatitis C antibody test is positive, then 
subjects must be tested for the presence of antigen by RT-PCR and subject must be HCV 
RNA negative. 
16. Serum pregnancy test (for females of childbearing potential) negative at screening. 
17. Female subjects of non-childbearing potential must meet at least 1 of the following 
criteria: 
a. Achieved postmenopausal status, defined as follows: cessation of regular menses for 
at least 12 consecutive months with no alternative pathological or physiological 
cause; status may be confirmed with a serum follicle stimulating hormone level 
confirming the postmenopausal state; 
b. Have undergone a documented hysterectomy and/or bilateral oophorectomy; 
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c. Have a medically confirmed ovarian failure. 
All other female subjects (including female subjects with tubal ligations) are considered 
to be of childbearing potential. 
Fertile male subjects and female subjects of childbearing potential must be willing to use 
a highly effective method of contraception as outlined in Section 4.4 for at least 
12 months (6 months for males) after the last documented use of cyclophosphamide. 
18. Evidence of a signed and dated informed consent document indicating that the subject 
has been informed of all pertinent aspects of the study. 
19. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and 
other procedures. 
4.2 
Exclusion Criteria 
1. Active central nervous system (CNS) involvement by malignancy.  Note: subjects with a 
history of CNS disease that has been effectively treated will be eligible. 
2. Clinically significant CNS dysfunction, eg, seizure disorder, cerebrovascular 
ischemia/hemorrhage, dementia, cerebellar disease, cerebral edema, posterior reversible 
encephalopathy syndrome, or any autoimmune disease with CNS involvement. 
3. Current thyroid disorder (including hyperthyroidism), except for subjects with 
hypothyroidism controlled on a stable dose of hormone replacement therapy. 
4. Any other active malignancies that required systemic treatment within 3 years prior to 
randomization (Note: cancers that can be adequately treated with local measures like 
surgical resection or local radiation with limited chance of recurrence or spread such as 
basal cell or squamous cell skin cancer, carcinoma in situ, or low Gleason score prostate 
cancers are acceptable). 
5. Radiation therapy within 2 weeks prior to lymphodepletion. 
6. Prior irradiation to >25% of the bone marrow. 
7. Hypocellular bone marrow for age by institutional standard as determined from a bone 
marrow biopsy performed at time of screening. 
8. Donor lymphocyte infusion within 30 days prior to lymphodepletion. 
9. Autologous or allogeneic HSCT within last 6 months (24 weeks) prior to 
lymphodepletion. 
10. Prior treatment with anti-CD19 targeted therapies (including CAR T cell therapy and 
bispecific antibodies, etc).  
11. Systemic anti-cancer therapy within 2 weeks prior to receiving lymphodepletion. If the 
last immediate anti-cancer treatment contained an antibody-based agent(s) (approved or 
investigational), then an interval of 28 days or 5 half-lives (whichever is shorter) of the 
agent(s) prior to receiving ALLO-647.  No bridging therapy (including corticosteroids for 
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disease management) is permitted during the screening period before initiating 
lymphodepletion. 
12. Participation in other studies involving investigational drug(s) within 28 days prior to 
lymphodepletion (with the exception of small molecule drugs for which only 14 days is 
required). 
13. Ongoing treatment with immunosuppressive agents; for example: 
a. Corticosteroid use within 1 week prior to first dose of lymphodepletion, with the 
exception of inhaled steroid for asthma, topical steroid use, or another local 
corticosteroid administration. Subjects requiring systemic steroids at daily doses >10 
mg prednisone (or corticosteroid equivalent), or those who are administered steroids 
for lymphoma control or WBC-count-lowering are not eligible for the study; 
b. Infliximab must be stopped at least 45 days prior to administration of ALLO-501A. 
14. Active and clinically significant autoimmune disease requiring systemic therapy within 
the last 2 years including, but not limited to, Guillain-Barre syndrome, amyotrophic 
lateral sclerosis, rheumatoid arthritis, systemic lupus erythematosus, other connective 
tissue disorders, vasculitis, inflammatory bowel disease, immune cytopenias, severe 
psoriasis, autoimmune hemolytic anemia or idiopathic thrombocytopenic purpura. 
15. Subject known to be refractory to platelet or red blood cell transfusions. 
16. Active acute or chronic graft-versus-host disease (GvHD), or GvHD requiring 
immunosuppressive treatment within 4 weeks of randomization. 
17. Subjects with active systemic bacterial, fungal, or viral infection requiring systemic 
treatment (including positive blood cultures within 7 days before starting 
lymphodepletion).   
a. Subjects must not be receiving systemic anti-infectious agent for the treatment of an 
active infection within 48 hours before ALLO-501A administration (prophylactic use 
is allowed). 
b. Subjects who are CMV seropositive at screening must demonstrate CMV clearance 
(with a qPCR result of not detected) prior to start of lymphodepletion. 
c. Subjects with untreated latent tuberculosis (by interferon gamma release assay 
[IGRA]) are not eligible. 
18. Any form of primary and acquired immunodeficiency (eg, severe combined 
immunodeficiency disease). 
19. Myocardial infarction or unstable angina within 6 months prior to screening, or unstable 
arrhythmia. 
20. Cardiac lymphoma involvement 
21. History of hypertension crisis or hypertensive encephalopathy within 6 months prior to 
screening. 
22. History of solid organ transplant (corneal transplant permitted). 
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23. History of hemophagocytic lymphohistiocytosis (HLH). 
24. History of progressive multifocal leukoencephalopathy (PML). 
25. Clinically significant liver disease, including viral or other hepatitis or cirrhosis 
26. Clinically significant pulmonary disease, such as severe COPD (Gold3, FEV1<50%), 
history of bronchospasm requiring intubation, interstitial lung disease, or pneumonitis 
(drug-related or autoimmune).  
27. Known or suspected hypersensitivity to murine and bovine products. 
28. Other acute or chronic medical or psychiatric condition or laboratory abnormality that 
may increase the risk associated with study participation in the judgment of the 
investigator 
29. Subjects unwilling to undergo an extended safety monitoring period (long-term follow 
up). 
30. Pregnant or breastfeeding or planning to become pregnant or breastfeed during the study 
or within 12 months (6 months for males) of last dose of cyclophosphamide. 
4.3 
Criteria for ALLO-501A Administration
 
Following lymphodepletion, subjects will be assessed for eligibility for ALLO-501A infusion 
on 
   
1. 
Adequate organ functions including renal and hepatic function based on the last 
assessment performed within the lymphodepletion period, defined as: 
a. 
Estimated creatinine clearance ≥50 mL/min (Cockcroft-Gault) or directly 
measured with 24-hour urine collection. 
b. 
AST and ALT ≤3 × ULN; ≤5.0 × ULN if there is liver involvement by the tumor.  
c. 
Alkaline phosphatase ≤2.5 × ULN (≤5 × ULN in case of bone metastasis).  
d. 
Total bilirubin ≤1.5 × ULN, except in subjects with Gilbert’s Syndrome who must 
have a total bilirubin ≤3 × ULN. 
2. 
No clinical signs of cardiac failure. 
3. 
No active systemic bacterial, fungal, protozoal, or viral infection not controlled by 
adequate treatment, and absence of positive blood cultures within 7 days before 
ALLO-501A administration. Subjects must be either: 
• 
fever free for ≥48 hours without anti-pyretic drug prior to ALLO-501A infusion, 
and must not be receiving systemic anti-infectious agent for the treatment of an 
active infection within 48 hours before ALLO-501A administration (prophylactic 
use is allowed), or 
• 
fever free on the day of ALLO-501 infusion in the case of fever due only to ALLO-
647 related infusion-related reaction 
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4. 
Normal SpO2 >92% on room air. 
5. 
Non-hematological toxicity must be resolved to baseline or Grade 1 prior to ALLO-
501A infusion. 
6. 
Absence of viral reactivation (asymptomatic viremia not clinically significant are 
allowed). 
7. 
No other medical condition(s) nor laboratory findings that, in the opinion of the 
investigator, might jeopardize subject’s safety. 
Two doses of tocilizumab must be available for each subject prior to infusion of ALLO-501A 
and ready for administration within 2 hours. In the event of a pandemic-related shortage, one 
dose of tocilizumab must be available on-site for immediate administration (within 2 hours), 
with access to an additional dose of tocilizumab within 8 hours after each previous dose of 
tocilizumab administered, if needed. In addition, a second line CRS agent must be available 
which, while not formally studied or FDA approved for use in CRS, have been used in CRS 
management (Riegler  et al, 2019). This may include the anti IL6 agent siltuximab and IL-1R 
inhibitor anakinra, depending on the institution’s CRS guidelines. 
If a subject does not meet the eligibility criteria for ALLO-501A administration, the 
ALLO-501A infusion must be delayed until the event resolves or returns to baseline, up to a 
maximum delay of 3 days. If the event is not resolved or does not return to baseline during 
the allowed delay time, ALLO-501A must not be administered unless otherwise agreed 
between the investigator and the sponsor. 
4.4 
Contraception Requirements 
All male subjects and female subjects who are of childbearing potential and who are sexually 
active and at risk for pregnancy with their partner(s) must agree to use a highly effective 
method of contraception consistently and correctly for the duration of the active treatment 
period and for at least 12 months (6 months for males) after the last dose of 
cyclophosphamide. The investigator or his or her designee, in consultation with the subject, 
will confirm that the subject has selected an appropriate method of contraception for the 
individual subject and his or her partner(s) from the permitted list of contraception methods 
(see below) and will confirm that the subject has been instructed in its consistent and correct 
use. At time points indicated in the Schedule of Activities, the investigator or designee will 
inform the subject of the need to use highly effective contraception consistently and correctly 
and document the conversation and the subject’s affirmation in the subject’s chart (subjects 
need to affirm their consistent and correct use of at least 1 of the selected methods of 
contraception). In addition, the investigator or designee will instruct the subject to call 
immediately if the selected contraception method is discontinued or if pregnancy is known or 
suspected in the subject or partner. 
Highly effective methods of contraception are those that, alone or in combination, result in a 
failure rate of less than 1% per year when used consistently and correctly (ie, perfect use) and 
include the following: 
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a. Established use of estrogen and progesterone-containing hormonal methods of 
contraception associated with inhibition of ovulation (eg, oral, inserted, injected, 
implanted, transdermal), provided the subject or male subject’s female partner plans to 
remain on the same treatment throughout the entire study and has been using that 
hormonal contraceptive for an adequate period of time to ensure effectiveness. 
b. Correctly placed copper containing intrauterine device. 
c. Intrauterine hormone-releasing system. 
d. Male sterilization with absence of sperm in the 90-day post-vasectomy ejaculate. 
e. Bilateral tubal ligation/bilateral salpingectomy or bilateral tubal occlusive procedure 
(provided that occlusion has been confirmed in accordance with the device’s label). 
NOTE: Sexual abstinence, defined as completely and persistently refraining from all 
heterosexual intercourse (including during the entire period of risk associated with the 
study treatments) may obviate the need for contraception ONLY if this is the preferred 
and usual lifestyle of the subject. 
4.5 
Sponsor’s Qualified Medical Personnel 
The contact information for the sponsor's appropriately qualified medical personnel for the 
study is documented in the study contact list located in the supporting study documentation. 
To facilitate access to appropriately qualified medical personnel on study related medical 
questions or problems, subjects are provided with a contact card. The contact card contains, 
at a minimum, protocol and investigational product identifiers, subject study numbers, 
contact information for the investigator site to provide advice on a medical question or 
problem originating from another healthcare professional not involved in the subject’s 
participation in the study. The contact number is not intended for use by the subject directly, 
and if a subject calls that number, he or she will be directed back to the investigator site. 
5. STUDY TREATMENTS 
For the purposes of this study, and per International Conference on Harmonization (ICH) 
guidelines, investigational product is defined as a pharmaceutical form of an active 
ingredient or placebo being tested or used as a reference/comparator in a clinical trial, 
including a product with a marketing authorization when used or assembled (formulated or 
packaged) in a way different from the approved form, or when used for an unapproved 
indication, or when used to gain further information about an approved use (ICH E6 1.33). 
For this study, the investigational products are ALLO-501A and ALLO-647.  
5.1 
Allocation to Treatment: Randomized Treatment Assignment: 
The medical monitor may review to confirm subject eligibility and approval for 
enrollment/randomization. Subject enrollment will be approved by the Sponsor. 
Treatment randomization will occur centrally. Subjects will be assigned randomly in a 1:1 
ratio to a lymphodepletion regimen of either FC or FCA.   
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Randomization will be stratified based on the following risk factors: 
 
Stratum 1:  ULN < LDH ≤ 2 x ULN and presence of lesion ≥5 cm (50 mm) 
 
Stratum 2:  LDH ≤ ULN or all lesions <5 cm    
5.2 
Investigational Product Compliance 
All doses of investigational products will be administered by the appropriately designated 
study staff at the investigational site. 
The site will complete required dosage Administration Record; template forms will be 
located in the IP manual. The use of the Administration Record is preferred but it does not 
preclude the use of an existing appropriate clinical site documentation system. The existing 
clinical site's documentation system should capture all pertinent /required information on the 
preparation and administration of the dose. This may be used in place of the Administration 
Record after approval from the sponsor and/or designee.  
5.3 
Investigational Medicinal Product Supplies  
5.3.1 
ALLO-501A  
ALLO-501A is the investigational medicinal product 1 (IMP1). 
5.4 
Dosage Form(s) and Packaging of ALLO-501A 
The ALLO-501A dosage form is composed of CAR+_TCRαβ−_CD52+/− CAR T cells 
formulated at 20 × 106 viable CAR+ T cells/mL in a commercially available cryopreservation 
media. ALLO-501A injection is presented as a sterile solution for IV administration. Each 
vial is sealed with a coated stopper and an overseal.  
The product is labeled according to local regulatory requirements. 
5.4.1.1 
Preparation and Dispensing of ALLO-501A 
See the IP manual for instructions on how to prepare the ALLO-501A for administration. 
ALLO-501A should be prepared and dispensed by an appropriately qualified and 
experienced member of the study staff (eg, physician, nurse, physician’s assistant, nurse 
practitioner, pharmacy assistant/technician, or pharmacist) as allowed by local, state, and 
institutional guidance. ALLO-501A vials are for single use only. 
Only qualified personnel who are familiar with procedures that minimize undue exposure to 
themselves and to the environment should undertake the preparation, handling, and safe 
disposal of ALLO-501A per the study IP manual. 
5.4.2 
ALLO-647  
ALLO-647 is the investigational medicinal product 2 (IMP2). 
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5.4.2.1 
Dosage Form(s) and Packaging of ALLO-647 
ALLO-647 drug product is provided as a 
 for intravenous administration in a 
glass vial at a concentration of 10 mg/mL. It is sealed with a coated stopper and an overseal, 
and labelled according to local regulatory requirements. The vial is designed for single use.  
5.4.2.2 
Preparation and Dispensing of ALLO-647 
See the IP manual for instructions on how to prepare the ALLO-647 for administration. 
ALLO-647 should be prepared and dispensed by an appropriately qualified and experienced 
member of the study staff (eg, physician, nurse, physician’s assistant, nurse practitioner, 
pharmacy assistant/technician, or pharmacist) as allowed by local, state, and institutional 
guidance. 
Only qualified personnel who are familiar with procedures that minimize undue exposure to 
themselves and to the environment should undertake the preparation, handling, and safe 
disposal of ALLO-647. 
5.5 
Non-Investigational Medicinal Product Supplies 
Central supply or locally obtained commercial supplies of these drugs will be used in 
accordance with local regulations and the package insert. Fludarabine and cyclophosphamide 
are approved/authorized chemotherapy agents, and are used for conditioning before 
autologous CD-19 CAR T therapy which has been approved at a minimum in the US and EU 
(Yescarta USPI, Yescarta SmPC, Kymriah USPI, Kymriah SmPC, Breyanzi USPI, Breyanzi 
EPAR). 
5.5.1 
Fludarabine 
Fludarabine phosphate is a synthetic purine nucleoside that differs from physiologic 
nucleosides in that the sugar moiety is arabinose instead of ribose or deoxyribose. 
Fludarabine is a purine antagonist antimetabolite. 
5.5.2 
Cyclophosphamide 
Cyclophosphamide is a nitrogen mustard-derivative alkylating agent. Following conversion 
to active metabolites in the liver, cyclophosphamide functions as an alkylating agent; the 
drug also possesses potent immunosuppressive activity.  
5.6 
Administration 
For specific details regarding administration of the non-IMPs, refer to the most recent version 
of the relevant prescribing information (Fludarabine USPI, Fludarabine SmPC; 
Cyclophosphamide USPI; Cyclophosphamide SmPC). 
5.6.1 
Fludarabine and Cyclophosphamide 
Subjects must be prepared for ALLO-501A administration with lymphodepletion. 
Lymphodepleting chemotherapy will be fludarabine and cyclophosphamide with or without 
ALLO-647.  
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Fludarabine 30 mg/m2 will be administered intravenously over approximately 15 to 30 
minutes for 
, from 
.   
Fludarabine dose should be reduced based on renal function.  Subjects with creatinine 
clearance 50 to 80 mL/min should have a 20% dose reduction of each daily fludarabine dose 
(ie, 20 mg/m2), or per institutional standard.   
Cyclophosphamide 300 mg/m2 will be administered intravenously over approximately 1 hr 
for 
, from 
.   
Chemotherapy, including anti-emetics and hydration, should be administered according to 
institutional guidelines.  Dexamethasone and other steroids are not to be administered as pre-
medications. 
Refer to the most recent version of the package insert for specific details surrounding the 
administration of non-IMPs. 
5.6.2 
ALLO-647 
For subjects randomized to the FCA arm, ALLO-647 will be administered IV over 
approximately 4 hours. ALLO-647 must be administered after the completion of FC. ALLO-
647 must not be infused concomitantly with other drug products.  
Subjects should be closely monitored up to 2 hours after the completion of the infusion or per 
institutional guidelines. 
Details for ALLO-647 infusion preparation are provided in the current IP manual. 
5.6.2.1 
Premedication Prior to ALLO-647 Infusion 
During treatment, subjects receiving ALLO-647 must receive premedication with 10 mg/kg 
hydrocortisone IV (or equivalent) or per institutional standard maximum daily dose prior to 
ALLO-647 infusion on 
 (as applicable according to the ALLO-647 
dose).   
Subjects will also receive a standardized non-steroid premedication for infusion-related 
reaction on each day of ALLO-647 infusion, or per institutional standard practices.  Subjects 
on the FC arm may receive premedications before fludarabine and/or cyclophosphamide per 
institutional standard practices: 
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Medication 
Premedication 
Fludarabine; Cyclophosphamide 
Premedications if per institutional standard practices 
ALLO-647 
Steroid:  Hydrocortisone 10 mg/kg IV (or equivalent) 
(or maximum daily dose) 
Antihistamine (eg, diphenhydramine) 
H2 blocker (eg, famotidine) 
Acetaminophen (paracetamol) 
Optional: long-acting non-sedating antihistamine 
ALLO-501A 
Premedications if per institutional standard practices 
 
5.6.2.2 
ALLO-647 Dose Interruption 
Subjects experiencing toxicity despite supportive care may have the infusion interrupted or 
stopped.  Appropriate follow-up assessments should be done until adequate recovery occurs 
as assessed by the investigator.  
In the event of an infusion-related reaction, the infusion rate of ALLO-647 may be decreased 
by up to 50% of original rate of infusion or interrupted until resolution of the event and re-
initiated until completion of the infusion (Appendix 6). If the infusion is not resumed and the 
patient received only a partial dose, the actual dose administered will be entered into the 
eCRF. 
Lymphodepletion may be delayed as needed until toxicity resolution, for up to 3 days.  
Resuming ALLO-647 following treatment interruption for treatment related toxicity may not 
occur until all of the following parameters have been met: 
• Non-hematologic toxicities have returned to baseline or Grade 1 severity (or, at the 
investigator’s discretion, Grade ≤2 if not considered a safety risk for the subject). 
If a dose interruption results from worsening of hematologic or biochemical parameters, the 
frequency of relevant blood tests should be increased as clinically indicated. 
5.6.3 
ALLO-501A 
Eligibility criteria for ALLO-501A administration will be assessed prior to infusion of 
ALLO-501A to ensure subjects’ safety (Section 4.3). 
Subjects will receive the intended dose of ALLO-501A treatment administered intravenously 
over approximately 5 minutes on
.   
Details for ALLO-501A infusion preparation are provided in the IP Manual. 
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Pre-treatment with antihistamine and acetaminophen (paracetamol) is permitted if per local 
institutional practices. 
If a subject does not meet the eligibility criteria allowing ALLO-501A administration due to 
an AE or other reason (in consultation with the medical monitor) (Section 4.3), ALLO-501A 
infusion must be delayed until the event resolves or returns to baseline, up to a maximum 
delay of 3 days (Section 4.3).  If the event is not resolved or does not return to baseline 
during the allowed delay time, ALLO-501A must not be administered unless otherwise 
agreed between the investigator and the sponsor. 
For ALLO-501A, there will be no dose decrease. 
5.7 
Study Stopping Criteria 
5.7.1 
Stopping Criteria for ALLO-647 
Accrual pausing criteria will be described in the Data Safety Monitoring Board charter. 
5.7.2 
Stopping Criteria for ALLO-501A 
If a Grade ≥2 steroid resistant/refractory acute GVHD event occurs, and the subject received 
>7 × 104/kg TCR positive cells, then accrual to the study will be paused for further safety 
review. 
5.8 
Medication Errors 
Safety Event 
Recorded on the eCRF 
Reported on the SAE Report Form to the Sponsor 
or Designee Within 24 Hours of Awareness 
Medication error 
All (regardless of whether 
associated with an AE) 
Only if associated with a SAE. 
 
Medication errors may result from the administration of the investigational product to the 
wrong subject, or at the wrong time, or at the wrong dosage strength.  
Medication errors include: 
• Medication errors involving subject exposure to the investigational product; 
• Potential medication errors or uses outside of what is foreseen in the protocol that do 
or do not involve the participating subject. 
Such medication errors occurring to a study participant are to be captured as a protocol 
deviation, on the appropriate product log page of the eCRF, and on the AE page if the 
medication error is related to an adverse event. Refer to the study eCRF completion 
guidelines for further instructions. 
In the event of medication dosing error, the sponsor should be notified immediately. 
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Medication errors should be reported to the sponsor or designee within 24 hours on the SAE 
report form only when associated with a serious adverse event. 
5.9 
Investigational Product Storage  
The investigator, or an approved representative, eg, pharmacist, will ensure that all 
investigational and non-investigational products are stored in a secured area with controlled 
access under required storage conditions and in accordance with applicable regulatory 
requirements.  Investigational products should be stored in their original containers and in 
accordance with the labels.  It is preferred that ALLO-501A be stored in the liquid nitrogen 
shipper until product preparation.   
See the IP manual for further details on storage and handling of ALLO-647 and ALLO-501A 
once diluted and package inserts for Flu/Cy for handling of those products once reconstituted 
and/or diluted.  
Site systems must be capable of measuring and documenting (eg, via a log), at a minimum, 
daily minimum and maximum temperatures for all site storage locations (as applicable, 
including frozen, refrigerated, and/or room-temperature products). This should be captured 
from the time of investigational product receipt throughout the study. 
Any excursions from the investigational product label storage conditions should be reported 
to Allogene immediately upon discovery.  The site should actively pursue options for 
returning the product to the storage conditions described in the labeling, as soon as possible.  
Deviations from the storage requirements, including any actions taken, must be documented 
and reported to Allogene. 
Once an excursion is identified, the investigational product must be quarantined and not used 
until Allogene provides permission to use the investigational product.  It will not be 
considered a protocol deviation if Allogene approves the use of the investigational product 
after the temperature excursion.  Use of the investigational product with a known temperature 
excursion or other product complaint prior to Allogene approval will be considered a 
protocol deviation.  
Specific details regarding information the site should report for each excursion will be 
provided to the site by sponsor or its designee.  
Receipt of materials, door opening and closing, and other routine handling operations where 
the products are briefly out of the temperature range described in the labeling are not 
considered excursions.  
5.10 
Investigational Product Accountability  
The appropriate, trained site staff will be required to maintain a record of the study treatment 
shipment documentation, study treatment inventory and study treatment accountability. 
Inventory and accountability records must be readily available to the study monitor, the 
sponsor, and any regulatory authority. Any study treatment destruction at the institution or by 
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institutional vendor must be performed ensuring compliance with 21 CFR 312.59 and ICH 
E6 8.4.2. 
5.10.1 
Return or Destruction of Investigational Product Supplies  
The sponsor or designee will provide guidance on the return or destruction of both used and 
unused investigational product (eg, at the site). If destruction is authorized by the sponsor to 
take place at the investigator site, the investigator must ensure that the materials are 
destroyed in compliance with applicable environmental regulations, institutional policy, and 
any special instructions provided by Allogene, and all destruction must be adequately 
documented.  
Any study treatment destruction at the institution or by an institutional vendor must be 
performed ensuring compliance with 21 CFR 312.59 and ICH GCP E6 4.6.  
Refer to the ALLO-501A and ALLO-647 IP manual for specific instructions on return or 
destruction of investigational products. 
5.11 
Concomitant Treatments 
Concomitant treatment considered necessary for the subject’s well-being may be given at the 
discretion of the treating physician, unless specified as a prohibited medication.   
All concomitant treatments, blood products, as well as nondrug interventions received by 
subjects will be recorded on the eCRF from screening through 3 months (90 days) after the 
ALLO-501A infusion, or initiation of a new anti-cancer therapy.  After 3 months of follow-
up, or initiation a new anti-cancer therapy, only targeted concomitant medication will be 
collected through 12 months including gammaglobulin, immunosuppressive drugs, anti-
infective drugs, vaccinations, and any therapy for the treatment of the subject’s disease (anti-
lymphoma therapies). 
New anti-cancer therapy administered must be entered in the eCRF. 
Administration of hematopoietic growth factors (filgrastim, pegfilgrastim) are permitted after 
randomization as needed for ANC <500/μL in accordance with local or institutional 
guidelines.  
IVIG administration in accordance with local and institutional guidelines is also permitted 
during screening and after randomization as needed to maintain an IgG serum concentration 
above 400 mg/dL. 
5.12 
Toxicity Mitigation and Management 
5.12.1 
Cytokine Release Syndrome 
Cytokine release syndrome (CRS) is a symptom complex associated with the use of 
monoclonal antibodies and adoptive cell therapies that activate lymphocytes. The condition 
results from the release of cytokines from cells targeted by antibodies, immune effector cells 
recruited to the tumor area and subject’s immune cells activated during this process. When 
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cytokines are released, a variety of clinical signs and symptoms associated with CRS present 
themselves including cardiac, gastrointestinal, laboratory (coagulation, renal and hepatic), 
neurological, respiratory, skin, vascular (hypotension), and constitutional (fever, rigors, 
headaches malaise, fatigue arthralgia, nausea and vomiting). CRS can range from mild, flu-
like symptoms to a severe life-threatening syndrome including progression to 
hemophagocytic lymphohistiocytosis. 
The severity of CRS will be assessed according to the American Society for Transplantation 
and Cellular Therapy (ASTCT; formerly American Society for Blood and Marrow 
Transplantation, ASBMT) grading criteria described by Lee et al (2019) (Table 1). A 
suggested treatment algorithm for the management of CRS is provided in Appendix 5.  
Table 1. ASTCT CRS Consensus Grading 
CRS 
Parameter 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Fevera 
Temperature 
≥38oC 
Temperature 
≥38oC 
Temperature 
≥38oC 
Temperature ≥38oC 
With 
Hypotension 
None 
Not requiring 
vasopressors 
Requiring a 
vasopressor with 
or without 
vasopressin 
Requiring multiple 
vasopressors 
(excluding 
vasopressin) 
And/orb 
Hypoxia 
None 
Requiring low-
flow nasal 
cannulac or blow-
by 
Requiring high-
flow nasal 
cannulac, 
facemask, 
nonrebreather 
mask, or Venturi 
mask 
Requiring positive 
pressure (eg, CPAP, 
BiPAP, intubation 
and mechanical 
ventilation) 
ASTCT (Lee et al 2019)  
Abbreviations: ASBMT = American Society for Blood and Marrow Transplantation; CRS = cytokine release syndrome; 
CTCAE = Common Terminology Criteria for Adverse Events 
Organ toxicities associated with CRS may be graded according to CTCAE v5.0 but they do not influence CRS grading. 
a Fever is defined as temperature ≥38°C not attributable to any other cause. In subjects who have CRS then receive 
antipyretic or anticytokine therapy such as tocilizumab or steroids, fever is no longer required to grade subsequent CRS 
severity. In this case, CRS grading is driven by hypotension and/or hypoxia. 
b CRS grade is determined by the more severe event: hypotension or hypoxia not attributable to any other cause. For 
example, a subject with temperature of 39.5°C, hypotension requiring 1 vasopressor, and hypoxia requiring low-flow 
nasal cannula is classified as grade 3 CRS. 
c Low-flow nasal cannula is defined as oxygen delivered at ≤6 L/minute. Low flow also includes blow-by oxygen delivery. 
High-flow nasal cannula is defined as oxygen delivered at >6 L/minute. 
 
Subjects shall be closely monitored for signs and symptoms of CRS, ie, fever, hypoxia, and 
hypotension. Subjects should be advised to seek immediate medical attention should signs or 
symptoms of CRS occur at any time. At the first sign of CRS, institute treatment with 
supportive care, tocilizumab, or tocilizumab, and corticosteroids as indicated. 
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Subjects who experience Grade 2 or higher CRS (eg, hypotension, not responsive to fluids, 
or hypoxia requiring supplemental oxygenation) should be monitored with continuous 
cardiac telemetry and pulse oximetry. For subjects experiencing Grade ≥3 CRS, an 
echocardiogram should be performed to assess cardiac function and subjects should be 
promptly considered for intensive care supportive therapy. 
5.12.1.1 
Hypotension and Renal Insufficiency in the Setting of CRS    
Hypotension and renal insufficiency should be treated as described here or according to 
medical judgment and institutional practice guidelines. Vigorous intravenous fluid hydration 
may be needed to manage hypotension and vascular leak in the setting of CRS. Subjects 
should be closely monitored to prevent fluid overload, and in some cases continuous veno-
venous hemodialysis may be required. Invasive hemodynamic monitoring, for example, with 
a pulmonary artery catheter, may be helpful to optimize fluid management in settings of 
concurrent severe capillary leak, aggressive IVF administration, and/or pulmonary edema. 
Anti-hypertensives should be withheld whenever blood pressure begins to decrease below 
baseline values. 
The baseline blood pressure is defined for this guideline as the average of all blood pressure 
readings obtained during the 24 hours prior to ALLO-501A infusion. The first treatment for 
hypotension is administration of IV normal saline boluses. 
• Subjects with a systolic blood pressure, diastolic blood pressure, or mean arterial 
pressure that is 80% or less of their baseline or less than the lower limit of normal 
should receive 1-liter normal saline bolus. 
• If the hypotension does not respond adequately within 1 hour, a second bolus at a 
volume per investigator discretion should be given. 
• If hypotension persists despite 2 fluid boluses, consideration should be given for 
monitoring in the intensive care unit and administering vasopressor support. 
These guidelines may be modified based on institutional guidelines and the clinical 
characteristics of individual subjects, such as pulmonary status, cardiac function, and other 
factors. 
5.12.1.2 
Cardiac Toxicity in the Setting of CRS 
Cardiac manifestations of CRS may include arrhythmias, decreased ejection fraction/heart 
failure, myocardial ischemia, and cardiac arrest. Tachycardia is common in the setting of 
CRS and medications to slow sinus tachycardia should be avoided. Hypotension should be 
managed as in Section 5.12.1.1. 
Subjects with persistent hypotension not responsive to fluids should be evaluated for 
decreased ejection fraction/heart failure by echocardiogram. These toxicities should be 
emergently managed per medical judgment and institutional practice guidelines. 
Subjects with ≥Grade 2 cardiac toxicity should be monitored with continuous cardiac 
telemetry and pulse oximetry. Tocilizumab and corticosteroids should be administered per 
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Appendix 5. Follow-up ECGs and echocardiograms are recommended to monitor the course 
of toxicity to potential resolution. 
5.12.2 
Neurologic Toxicity 
Neurologic toxicities that were fatal or life-threatening occurred following treatment with 
autologous CAR T cell therapies. The most common neurologic toxicities included 
encephalopathy, headache, tremor, dizziness, aphasia, delirium, insomnia, and anxiety. 
Subjects who experience Grade 2 or higher neurologic toxicities should be monitored with 
continuous cardiac telemetry and pulse oximetry. Intensive care supportive therapy should be 
provided for Grade ≥3 neurologic toxicities. Non-sedating, anti-seizure medicines 
(eg, levetiracetam) for seizure prophylaxis should be considered for any Grade 2 or higher 
neurologic toxicities. In the event of Grade ≥3 neurological toxicity suspected related to 
ALLO-501A, a lumbar puncture should be performed, if safe to do so, and CSF collected, for 
infectious workup (including HHV6 and HHV7). If neurologic toxicity is suspected, the 
recommendations presented in Appendix 10 should be closely followed. For AEs of 
neurological toxicity, a neurotoxicity (ICANS) eCRF should be completed in the EDC, 
including the Immune Effector Cell-Associated Encephalopathy (ICE)  score. When relevant 
an assessment for new or reoccurrence of CNS disease should be considered including MRI. 
In general, neurological toxicities will graded according to CTCAE version 5.0. The ASTCT 
recently developed the immune effector cell-associated neurotoxicity syndrome (ICANS) 
consensus grading guidelines (Lee et al, 2019), which are provided in Appendix 8. The ICE 
assessment tool is incorporated into the grading of ICANS and is also provided in Appendix 
9.  In the event of ICANS or Grade ≥3 neurotoxicity data specific to the ASTCT ICANS 
consensus definition, including the ICE assessment will be collected on the SAE/AESI/eCRF 
form as outlined in the safety reporting guidance. Events of Grade ≥3 neurological toxicity 
are considered an AESI and require reporting to the sponsor within 24 hours of awareness. 
5.12.3 
Anti-Infective Prophylaxis 
Similar to alemtuzumab, ALLO-647 may be associated with prolonged and severe 
lymphopenia. and the effects of ALLO-501A on normal B cells may lead to B cell depletion and 
hypogammaglobulinemia, therefore, patients will be at increased risk for infection.  
Subjects should follow institutional guidelines for food hygiene, mask wearing in high-risk 
situations and maintain hand hygiene. Subjects should receive inactivated or recombinant 
influenza vaccine annually and follow local guidelines regarding vaccination for COVID-19 
(see Section 5.13.3). 
Protocol inclusion and exclusions regarding infections are outlined in Section 4.1 and Section 
4.2. 
For subjects living in or travelling to endemic areas screening should be considered for West 
Nile Virus, Strongyloides, Cocciomycosis, and Histoplamosis.  Serum Aspergillus 
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galactomannan antigen should be performed in subjects with a past history of invasive 
aspergillosis and other high-risk patients. 
Subjects in FC and FCA arms shall receive anti-infective prophylaxis as recommended by 
the US National Comprehensive Cancer Network for subjects receiving fludarabine, 
alemtuzumab (NCCN Guidelines, 2020), or per institutional guidelines. Any anti-infective 
prophylaxis administered will be recorded in the eCRF. Refer to the full prescribing 
information for a complete description of the individual product. 
From Day −5 until the ANC is >500 cells/µL, all subjects are recommended to receive the 
following anti-infective prophylaxis (or per institutional guidelines): 
• 
Bacterial – fluoroquinolone prophylaxis during neutropenia.  If intolerant to 
fluoroquinolone, consider TMP/SMX or an oral their-generation cephalosporin. 
• 
Fungal – posaconazole or voriconazole. Both posaconazole and voriconazole are 
potent inhibitors of hepatic cytochrome P450 3A4 (CYP3A4) isoenzymes and may 
significantly decrease the clearance of agents which are sensitive substrates of 
CYP3A4. Examples of CYP3A4 substrates can be found in Drug Development and 
Drug Interactions: Table of Substrates, Inhibitors and Inducers (Drug Interactions, 
2020). 
• 
Pneumocystis jirovecii prophylaxis (PCP) – TMP/SMX. The following agents can 
also be considered: atovaquone, dapsone, pentamidine (aerosolized or IV). 
From Day −5 for a minimum of 2 months after FC or FCA and until the CD4 count is 
>200 cells/µL: 
• 
Prophylaxis for herpes viruses – acyclovir, famciclovir, valacyclovir  
CMV Prophylaxis and Surveillance: 
• 
FCA subjects who are CMV-seropositive at screening receive antiviral therapy for 
CMV prophylaxis (recommend letermovir [480 mg administered orally once daily for 
100 days, or longer if clinically indicated beginning during lymphodepletion; 
intravenous prophylaxis should only be used if clinically necessary]).  CMV-
seropositive subjects on the FC arm may receive letermovir at the investigator’s 
discretion. 
• 
All subjects who are CMV seronegative at baseline should consider condom use to 
prevent primary infection via sexual intercourse. 
• 
Consists of weekly monitoring by PCR for a minimum of 2 months after FC or FCA. 
• 
In case of CMV reactivation, administer therapy per institutional standards 
(valganciclovir, ganciclovir, other recommended agents) or per guidance of local 
Infectious Disease specialists.   
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• 
If CMV remains detectable or in case of viral infection, further ID evaluation is 
recommended. 
Subjects should receive inactivated or recombinant influenza vaccine annually. 
5.12.4 
B Cell Depletion 
It is possible that B cell depletion and hypogammaglobulinemia will occur due to the effects 
of ALLO-501A on normal B cells. Gamma globulin will be administered for 
hypogammaglobulinemia according to institutional guidelines. At a minimum, trough IgG 
levels should be kept above 400 mg/dL including at baseline, and as indicated, especially in 
the setting of infection (ie, American Society for Blood and Marrow Transplantation, Center 
for International Bone Marrow Transplant Research; Hill et al, 2019). 
5.12.5 
Graft Versus Host Disease  
Cutaneous Grade 1 acute GvHD will be managed with topical corticosteroids. In case of Grade 
>2 acute GvHD, institutional guidelines for the treatment of GvHD will be applied and could 
include the use of systemic corticosteroids. Investigators are advised to activate the 
rituximab-induced ablation of ALLO-501A in case of steroid resistant/refractory acute 
GvHD; up to 4 weekly doses of 375 mg/m2 is recommended.  
A system to grade the severity of acute GVHD is provided in Appendix 3. 
The monitoring of chronic GvHD will be pursued for at least 2 years after the last 
ALLO-501A infusion. The National Institutes of Health Consensus Development Project on 
Criteria for Clinical Trials in Chronic Graft-versus-Host Disease has issued the staging 
classification, provided in Appendix 4. Institutional guidelines for the treatment of chronic 
GVHD should be applied. 
5.12.6 
Infusion-Related Reactions 
Following the first infusion of some therapeutic mAbs, subjects may experience infusion-
related reactions characterized by fever and chills, and less commonly, hypotension, 
headache, nausea, or vomiting. These adverse events are generally ascribed to lysis of the 
cellular targets, cytokine release, or complement activation. 
In the event of infusion related reactions, the investigator should institute treatment measures 
according to best medical and nursing practice. A suggested treatment algorithm for the 
management of infusion-related reactions is provided in Appendix 6; however, if local 
standard of care is a different regimen, it should be utilized.  
Details on pre-medications to be administered prior to ALLO-647 are provided in Section 
5.6.2.1.  The pretreatment medications will not be supplied by Allogene.  
Detailed guidance on treatment and dose interruption is provided in Appendix 6. 
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5.12.7 
Blood Product Support for Anemia and Thrombocytopenia 
All blood products should be irradiated and leukocyte reduced. Using CBCs as a guide, the 
subject should receive platelets and packed red blood cells as needed per institutional 
guidelines. Cross-match-compatible blood products for transfusion should be used where 
feasible. Leukocyte filters should be utilized for all blood and platelet transfusions to 
decrease sensitization to transfused WBCs and decrease the risk of cytomegalovirus 
infection.  
5.12.8 
Fever and Neutropenia 
Evaluation for a source of infection should be performed per institutional guidelines. Fevers 
should be treated with acetaminophen and comfort measures. NSAIDs and corticosteroids 
should be avoided. Subjects who are neutropenic and febrile should receive broad-spectrum 
antibiotics. Maintenance IV fluids (normal saline) should be started on most subjects with 
high fevers, especially if oral intake is poor or if the subject has tachycardia. G-CSF (eg, 
filgrastim, or biosimilars) should be used according to published guidelines (eg, Infectious 
Disease Society of America). Subjects who develop prolonged neutropenia should be 
managed according to the institutional guidance. Alternate reasons for the prolonged 
neutropenia e.g. viral (CMV, EBV, Parvovirus 19, ADV, HHV-6), drug related, and 
metabolic causes should be ruled out. A thorough evaluation for acquired bone marrow 
failure syndromes should be performed where clinically indicated. This may include 
performing bone marrow biopsy, and testing for TCR-beta clonality on the bone marrow 
sample when clinically indicated. Myelosuppressive medications should also be avoided.  
5.12.9 
Hematopoietic Growth Factors 
Primary prophylactic use of granulocyte colony stimulating factors is permitted to treat 
expected treatment emergent neutropenia as indicated by the current American Society of 
Clinical Oncology guidelines. Administration of filgrastim or pegfilgrastim (or biosimilars of 
either) is permitted per protocol and recommended for ANC <500 cells/µL following 
lymphodepletion and CAR+ T cell infusion in accordance with local or institutional 
guidelines. 
Erythropoietin may be used at the investigator’s discretion for the supportive treatment of 
anemia. 
5.12.10 
Anti-Diarrheal, Anti-Emetic Therapy  
Primary prophylaxis of diarrhea, nausea and vomiting is permitted at the investigator’s 
discretion. The choice of the prophylactic drug as well as the duration of treatment is up to 
the investigator assuming there is no known or expected drug-drug interaction and assuming 
the drug is not included in the Prohibited Treatment(s) section (Section 5.13). 
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5.13 
Prohibited Treatments 
5.13.1 
Anti-Inflammatory Therapy 
Systemic steroids must not be administered within 2 days prior to ALLO-501A (except to 
treat or prevent ALLO-647 infusion reactions). Other steroid use should be checked with the 
sponsor before starting lymphodepletion. 
Corticosteroids and other immunosuppressive drugs should also be avoided for 3 months 
after ALLO-501A infusion, unless used to manage ALLO-501A or ALLO-647 related 
toxicities. Acute emergency administration, topical applications, inhaled sprays, eye drops, or 
local injections of corticosteroids are allowed. 
Other medications that might interfere with the evaluation of the investigational product, 
such as non-steroidal anti-inflammatory agents, should also be avoided for the same time 
period unless medically necessary. 
5.13.2 
Other Antitumor/Anticancer or Experimental Drugs 
No additional radiation or systemic anti-tumor treatment will be permitted until documented 
progressive disease, unless otherwise specified in this protocol.  
There is no information on potential interactions with the concurrent use of select vitamins or 
herbal supplements, therefore their use should be avoided. 
5.13.3 
Viral vaccines 
The safety of immunization with live viral vaccines during or following ALLO-501A 
treatment has not been studied. Vaccination with live virus vaccines is not recommended for 
at least 6 weeks prior to the start of lymphodepleting regimen, during ALLO-501A treatment, 
and until immune recovery following treatment with ALLO-501A. 
The administration of COVID-19 vaccines which have been authorized by Health Authorities 
under an Emergency Use Authorization (EUA) or equivalent is permitted on study, as per 
institutional guidelines. 
6. STUDY PROCEDURES  
For an individual subject, the study will be divided in different periods including pre-
screening (optional), screening, lymphodepletion, treatment, and follow-up.  
6.1 
Prescreening 
Prescreening period is optional and may be used for the assessment of the absence of donor-
specific anti-human leukocyte antigen (HLA) antibodies prior to a subject entering the 
screening period. The results may be used to determine a subject’s eligibility for study 
participation.  
All subjects being considered for the study and eligible for optional pre-screening must sign a 
pre-screening informed consent form before completing any study-specific pre-screening 
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procedures. The investigator (or appropriate delegate at the site) will obtain informed consent 
from each subject in accordance with the procedures described in the Schedule of Activities 
and on the informed consent form. A subject identification number will be assigned after the 
form has been signed and upon entering the subject into pre-screening in the eCRF. 
Donor-specific anti-HLA antibody assessment completed during pre-screening must be 
repeated at screening if subject receives a transfusion (ie, red blood cells, platelets, plasma) 
between time of pre-screening and screening. 
6.2 
Screening 
All subjects being considered for the study and eligible for screening must sign an informed 
consent form before completing any study-specific procedures. The investigator (or 
appropriate delegate at the site) will obtain informed consent from each subject in accordance 
with the procedures described in the Schedule of Activities and on the informed consent 
form. A subject identification number will be assigned after the form has been signed and 
upon entering the subject into screening in the eCRF.  
For screening procedures see the Schedule of Activities. 
Screening will start after the informed consent form is signed. Subject’s eligibility criteria 
will be checked. The Screening period 
. Sponsor may request the 
review of selected screening assessments prior to randomization.  Subjects who meet all 
eligibility criteria at the end of the Screening period will then enter the Lymphodepletion 
Period.  Screening assessments may be repeated to meet eligibility. 
Screen failures are defined as participants who consent to participate in the clinical trial, who 
do not meet one or more criteria required for participation in the trial during the screening 
period and are not subsequently entered in the study. A minimal set of screen failure 
information is required to ensure transparent reporting of screen failure participants, to meet 
the Consolidated Standards of Reporting Trials (CONSORT) publishing requirements and to 
respond to queries from regulatory authorities. Minimal information includes demography, 
screen failure details, eligibility criteria, and any SAE. This information will be captured in 
the eCRF and in site source documents (patient medical record). 
Individuals who do not meet the criteria for participation in this trial (screen failure) may be 
rescreened. Refer to the eCRF completion guidelines for assignment of subject identification 
numbers for rescreened participants. 
6.3 
Lymphodepletion 
Lymphodepletion begins on 
.   
For procedures performed during the lymphodepletion period, see Section 6 and the Schedule 
of Activities. 
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6.4 
Treatment  
Treatment will be on 
 with the administration of ALLO-501A. 
For procedures performed during the treatment period, see Section 6 and the Schedule of 
Activities. 
6.5 
Follow-up  
6.5.1 
Follow-up for Subjects Completing Treatment 
For subjects treated with ALLO-501A, follow-up in this study will last through 
.  
For follow up procedures see the Schedule of Activities and Study Assessments (Section 6), 
and Appendix 11 for a summary of follow-up after disease progression. 
During follow-up, subjects who completed treatment and subsequently have documented 
radiographic disease progression may be treated with anti-cancer therapy including 
investigational trials, while remaining in follow-up for safety and survival follow-up in this 
study.  Scans documenting disease progression, including additional scans if available, must 
be sent to the IRC for central review. 
If a subject starts a new anti-cancer therapy, no further disease assessments, local blood 
analyses, and central research samples (except described below) are necessary, however, the 
subject should continue to be followed to the extent possible for:   
• Related serious adverse events as well as events relevant for long-term follow-up:  
new incidence of infection (potentially product-related), malignancy(ies), and/or 
hematologic disorder, as well as new incidence or exacerbation of a pre-existing 
neurologic, prior rheumatologic, or other autoimmune disorder (Section 8.1.3). 
• Targeted concomitant medications (Section 5.11) including gamma globulin, 
immunosuppressive drugs, anti-infective drugs, vaccinations, and any therapy for the 
treatment of the subject’s disease (anti-lymphoma therapies). 
• Blood sample for RCL, genomic safety biospecimen, and PBMCs (Schedule of 
Activities). 
• Survival status (Section 6.6) 
Subjects who experience progressive disease but do not start a new anti-cancer therapy do 
not need to complete additional disease assessments.  They should continue to be followed 
per the above bullet points with the following adjustment: 
• Subjects experiencing progression before three months (from Day 0) should continue 
to report AEs through 3 months and then transition to reporting only related serious 
adverse events (Section 8.1.3) 
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At the EOS visit, or at the time of withdrawal from the study, subjects will be asked to 
participate in a noninterventional safety-monitoring long term follow-up (LTFU) study.  In 
that study, subjects treated with ALLO-501A will be followed for a total of 15 years per 
requirement of the regulatory authorities for the follow-up of any subject having received a 
gene therapy treatment. 
6.5.2 
Follow-up after Randomization when subject did not receive study treatment 
For all randomized subjects who do not receive study treatment, provide tumor assessment 
data (imaging or similar) until disease progression or death is observed, or study completion 
at 
, whichever is earlier.  Safety assessments do not need to be completed. 
After disease progression, they should be followed for subsequent anti-cancer therapies, and 
survival only, until the study is completed.  No other clinic visits or assessments are required. 
Subjects who received no study treatment may be treated with anti-cancer therapy including 
investigational trials, while remaining in follow-up for safety and survival in this study. 
Reasons for not receiving any study treatment include: 
• Infection or adverse event (which precludes dosing) 
• Disease progression (clinical) 
• Full consent withdrawal   
6.5.3 
Follow-up after Randomization and Lymphodepletion when subject did not 
receive ALLO-501A 
If a subject is randomized and receives lymphodepletion including at least 1 dose of FC or 
ALLO-647, but does not receive ALLO-501A, provide tumor assessment data (imaging or 
similar) until disease progression or death is observed, or study completion at Month 60, 
whichever is earlier.  Also complete study safety visits including laboratory assessments 
relative to FC or FCA.   
After disease progression, they should be followed as described in Section 6.5.1  including 
subsequent anti-cancer therapies, safety, and survival, until the study is completed.    Blood 
samples for RCL and participation in the 15-year follow-up are not required if the subjects 
did not receive ALLO-501A CAR T cells.  Subjects who received partial treatment (and not 
ALLO-501A) may be treated with anti-cancer therapy including investigational trials, while 
remaining in follow-up for safety and survival in this study. 
Reasons for withdrawal from ALLO-501A treatment include: 
• Infection or adverse event (which precludes dosing) 
• Disease progression (clinical) 
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• Full consent withdrawal  
6.6 
Survival Follow-up 
For subjects who decline further protocol-required procedures or assessments after starting a 
new anti-cancer therapy, subjects can be contacted to assess survival status by clinic visit or 
telephone to assess survival until death, withdrawal by subject, lost to follow-up, or study 
terminated by Sponsor, whichever comes first. 
6.7 
Subject Withdrawal  
6.7.1 
Reasons for Withdrawal from Study (End of Study) 
Reasons for withdrawal from the study include: 
1 Full withdrawal of consent (see Section 6.7.2) 
2 Lost to follow-up (see Section 6.7.3) 
3 Death 
4 Completed study 
If a subject does not return for a scheduled visit, every effort should be made to contact the 
subject. In any circumstance, every effort should be made to document subject outcome, if 
possible. The investigator should inquire about the reason for withdrawal, request that the 
subject return for the EOS visit and follow up with the subject regarding any unresolved AEs 
6.7.2 
Withdrawal of consent:  
Subjects have the right to withdraw from the study at any time and for any reason without 
prejudice to his or her future medical care by the physician or at the institution.   
Subjects can decline to continue to receive study required treatment and/or other protocol 
required procedures at any time during the study but continue to participate in the study.  
If the subject declines continuing protocol required procedures, the investigator must discuss 
with the subject the appropriate process for discontinuation from investigational product, 
study treatment or other protocol required therapies and must discuss options for 
continued participation, completion of procedures and the associated data collection as 
outlined in the Schedule of Activities. The level of follow-up and method of 
communication should also be discussed between the research staff and the subject 
and documented in the source documents.    
Withdraw of consent for a study means that the subject does not wish to receive further 
protocol required therapy or undergo procedures and the subject does not wish to continue 
further study follow-up.  Subject data collected up to withdraw of consent will be 
retained and included in the analysis of the study, and where permitted by local regulations, 
publicly available data (death records) can be included after withdrawal of consent. The 
investigator is to discuss with the subject appropriate procedures for withdrawal from the 
study. 
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As part of the study, sites may be asked to conduct searches of public records, such as those 
establishing survival status, if available, to obtain survival data for any subject for whom the 
survival status is not known. Sites may be also asked to also retrieve autopsy reports to 
confirm status of disease at the time of death.  
The investigator and/or sponsor can also decide to withdraw a subject from the 
investigational product and/or other protocol-required therapies, or protocol procedures, at 
any time prior to study completion. 
6.7.3 
Lost to follow-up:  
All reasonable efforts must be made to locate subjects to determine and report their ongoing 
status. This includes follow-up with persons authorized by the subject as noted above. Lost to 
follow-up is defined by the inability to reach the subject after a minimum of 2 documented 
phone calls, faxes, or e-mails as well as lack of response by the subject to 1 registered mail 
letter. All attempts should be documented in the subject’s study source records. The site staff 
will consult publicly available sources, such as public health registries and databases, to 
obtain updated contact information. If, after all attempts, the subject remains lost to 
follow-up, then the last-known-alive date as determined by the investigator should be 
reported and documented in the subject’s study source records and in the eCRF. If it is 
determined that the subject has died, the site will use locally permissible methods to obtain 
the date and cause of death. If the investigator’s use of a third-party representative to assist in 
the follow-up portion of the study has been included in the subject’s informed consent, then 
the investigator may use a third-party representative to assist site staff with obtaining the 
subject’s contact information or other public vital status data necessary to complete the 
follow-up portion of the study.  
Subjects may withdraw from treatment at any time at their own request, or they may be 
withdrawn at any time at the discretion of the investigator or sponsor for safety or behavioral 
reasons, or the inability of the subject to comply with the protocol-required schedule of study 
visits or procedures at a given investigator site.  
7. ASSESSMENTS 
Every effort should be made to ensure that the protocol -required tests and procedures are 
completed as described. However, it is anticipated that from time to time there may be 
circumstances outside of the control of the investigator that may make it unfeasible to 
perform the test. In these cases, the investigator will take all steps necessary to ensure the 
safety and well-being of the subject. When a protocol-required test cannot be performed, this 
will be recorded as a protocol deviation (see Section 11.3). The study team will be informed 
of these incidents in a timely manner.  
For samples being collected and shipped to central laboratories, detailed collection, 
processing, storage, shipment instructions and contact information will be provided in the 
study central laboratory manual. 
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7.1 
Safety Assessment 
Safety assessments will include collection of AEs, SAEs, vital signs and physical 
examination, electrocardiogram (ECG [12-lead]), laboratory assessments, including 
pregnancy tests and verification of concomitant treatments. 
7.1.1 
Adverse Events 
Assessment of adverse events will include the type, incidence, severity (graded by the NCI 
CTCAE version 5.0, unless otherwise specified) timing, seriousness, and relatedness (see 
Section 8). The severity of CRS and neurotoxicity will be assessed according to the grading 
described in Table 1 and Appendix 9, respectively. The severity of acute graft versus host 
disease will be assessed according to the grading described in Appendix 3.  
7.1.2 
Laboratory Safety Assessment 
Hematology and blood chemistry will be drawn at the time points described in the Schedule 
of Activities and analyzed at local laboratories unless otherwise stated in Table 2. 
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Table 2. Safety Laboratory Tests 
Hematology 
Chemistry 
Infection 
Coagulation 
Urinalysis 
Pregnancy 
Test 
Hemoglobin 
and hematocrit  
ALT 
Serologies for 
HBV and HCV 
PT or INR 
Urine dipstick 
for protein, 
glucose, 
creatinine, and 
blood: If 
positive collect 
24-hr and/or 
microscopic 
cell count 
(Reflex 
Testing) 
For female 
subjects of 
childbearing 
potential, 
serum 
Platelets 
AST 
PTT 
WBC 
Alk Phos 
Fibrinogen 
Absolute/% 
Neutrophils 
Sodium 
RCL 
(Central 
laboratory) 
D-Dimers 
Absolute/% 
Lymphocytes 
Potassium 
Aerobic and 
anaerobic 
blood cultures 
 
Absolute/% 
Monocytes 
Magnesium 
 
Absolute/% 
Eosinophils 
Chloride 
Absolute/% 
Basophils 
Serum calcium 
Interferon 
gamma release 
assay (IGRA) 
for latent TB 
 
Screening for 
endemic 
infections as 
needed 
 
Screening and 
Monitoring for 
CMV and EBV 
and adenovirus 
if indicated 
Reticulocyte 
count 
Total bilirubina 
BUN or Urea 
 
Creatinine 
Creatinine 
clearance 
 
Uric Acid 
Glucose  
LDH 
Albumin 
Phosphorus or 
Phosphate 
Bicarbonate 
Total Protein 
TSH 
Ferritin 
CRP 
 
Abbreviations: Alk Phos = alkaline phosphatase, ALT = alanine aminotransferase, AST = aspartate 
aminotransferase, BUN = blood urea nitrogen, CMV = cytomegalovirus, CRP = C-reactive protein, EBV = 
Epstein-Barr virus, HBC = hepatitis B core, HCV = hepatitis C virus,  
INR = international normalized ratio, LDH = lactate dehydrogenase, PT = prothrombin time, PTT = partial 
thromboplastin time, RCL = replication competent lentivirus, TB = tuberculosis, TSH = thyroid stimulating 
hormone, WBC = white blood cell 
a For potential Hy's Law cases, in addition to repeating AST and ALT, laboratory tests should include albumin, 
creatine kinase, total bilirubin, direct and indirect bilirubin, gamma-glutamyl transferase, prothrombin time 
(PT)/INR, alkaline phosphatase, total bile acids and acetaminophen drug and/or protein adduct levels.  
7.1.3 
Vital Signs and Physical Examination 
Subjects will have a physical examination to include weight, vital signs, Immune Effector 
Cell-Associated Encephalopathy (ICE) score (baseline and as clinically indicated), 
neurological exam, assessment of ECOG performance status (Appendix 2), and height; 
height will be measured at baseline only.  
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7.1.4 
Electrocardiogram (12-Lead) 
At each time point (see Schedule of Activities), a single ECG should be performed to for 
cardiac safety and to  determine the QTcF (Fridericia’s) interval.  If the QTcF is prolonged 
(>500 msec, ie, CTCAE Grade 3) (except with underlying bundle branch block), then the 
ECG should be re-evaluated by a qualified person at the site for confirmation as soon as the 
finding is made, including verification that the machine reading is accurate.  If manual 
reading verifies a QTcF of > 500 msec, immediate correction for reversible causes (including 
electrolyte abnormalities, hypoxia and concomitant medications for drugs with the potential 
to prolong the QTcF interval) should be performed.  In addition, repeat ECGs should be 
performed hourly for at least 3 hours until the QTcF interval falls below 500 msec.  If QTcF 
interval reverts to less than 480 msec, and in the judgment of the investigator(s) and sponsor 
is determined to be due to cause(s) other than investigational product, treatment may be 
continued with regular ECG monitoring.  If in that timeframe the QTcF intervals rise above 
500 msec the investigational products will be held until the QTcF interval decreases to 
480 msec.  If the QTcF interval has still not decreased to ≤480 msec after 2 weeks, or if at 
any time a subject has a QTcF interval >515 msec or becomes symptomatic, the 
investigational product will be stopped.  An additional ECG may be performed as clinically 
indicated.  
Prior to concluding that an episode of prolongation of the QTcF interval is due to 
investigational product, thorough consideration should be given to potential precipitating 
factors (eg, change in subject clinical condition, effect of concurrent medication, electrolyte 
disturbance) and evaluation by specialist should be considered. 
If a subject experiences a cardiac or neurologic AE (specifically syncope, dizziness, seizures, 
or stroke), an ECG (triplicate) should be obtained at the time of the event.    
7.1.5 
Echocardiogram or Multigated Acquisition Scan  
LVEF will be assessed by echocardiography (ECHO) or multi-gated acquisition scan 
(MUGA) at Screening.  
The same technique that was used during Screening should be used for a given subject 
throughout the study. The Simpson’s method is the most commonly used method and the one 
recommended for LVEF measurement. 
7.1.6 
Pregnancy Testing 
For female subjects of childbearing potential, a serum pregnancy test, with sensitivity of at 
least 25 mIU/mL, will be performed at screening and following timepoints defined in the 
Schedule of Activities. 
A negative pregnancy test result is required before the subject may receive the investigational 
products. Pregnancy tests will also be done whenever 1 menstrual cycle is missed (or when 
potential pregnancy is otherwise suspected). Pregnancy tests may also be repeated if 
requested by institutional review boards (IRBs)/ethics committees (ECs) or if required by 
local regulations. 
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7.2 
Tumor Response Assessment 
Subjects will be evaluated for disease response by the site investigator at times indicated in 
the Schedule of Activities. Disease assessments will be evaluated per the Lugano 
classification criteria 2014 (Cheson et al, 2014). Flow cytometric, molecular or cytogenetic 
studies will not be used to determine response. 
Tumor assessments will include all known or suspected disease sites.  Disease-specific 
imaging as clinically appropriate will be performed.  Anti-cancer activity will be assessed at 
baseline, during treatment as specified in the Schedule of Activities, and whenever disease 
progression is suspected (eg, symptomatic deterioration). 
Disease assessments after ALLO-501A will be used to determine the time when PD occurs. 
Subjects with symptoms suggestive of disease progression should be evaluated for 
progression at the time symptoms occur even if it is off schedule as per the Schedule of 
Activities. 
A bone marrow aspirate and biopsy will be performed in subjects who are being assessed for 
CR. Per the revised IWG Response Criteria for Malignant Lymphoma (Cheson et al, 2014), a 
bone marrow aspirate and biopsy should be performed only when the subject had bone 
marrow involvement with lymphoma prior to randomization or if new abnormalities in the 
peripheral blood counts or blood smear cause clinical suspicion of bone marrow involvement 
with lymphoma after randomization. For treatment response confirmation, the bone marrow 
aspirate and biopsy must show no evidence of disease by morphology, or if indeterminate by 
morphology, it must be negative by immunohistochemistry to assign a CR to treatment. 
All subjects’ files and radiologic images must be available for source verification by the  
sponsor. 
7.2.1 
Imaging Assessments for Independent Review Committee 
In addition to the investigator’s assessment, disease-specific imaging as clinically 
appropriated, and additional clinical data will be submitted to and reviewed by the central 
radiology vendor (IRC) per the instructions in the imaging manual. For subjects who 
discontinue the study due to an assessment of PD, any additional imaging data, current and 
subsequent to the image in question, will be submitted to the central reviewer to confirm 
disease response. 
Imaging requirements, specifications, and transmittal requirements are outlined in the study 
imaging manual. 
7.3 
 Cell Kinetics and Pharmacokinetics Assessments 
Biospecimens will be collected at various time points and examined using cellular, molecular 
and protein-based assays such as an ELISA-based monitoring of ALLO-647, fludarabine, 
and cyclophosphamide PK, vector copy number (VCN) analysis by qPCR, and cellular 
kinetics analysis by flow cytometry. Samples for ALLO-501A and ALLO-647, fludarabine, 
and cyclophosphamide monitoring will be collected into appropriately labeled tubes as 
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outlined in the Schedule of Activities and central laboratory manual. The cellular kinetics and 
PK sampling schedule may be modified based on emerging cellular kinetics and PK data.  
In addition to samples collected at the scheduled times, an additional blood sample should be 
collected from subjects experiencing unexpected and/or serious AEs and the date and time of 
blood sample collection will be documented in the eCRF and source records. Such samples 
may be used to explore levels of ALLO-501A cells in subjects experiencing unexpected 
and/or SAEs. 
Where noted in the Schedule of Activities, blood samples for ALLO-647, fludarabine, and 
cyclophosphamide concentrations and ALLO-501A cellular kinetics assessment will be 
collected at approximately the same time as other assessments such as pharmacodynamics, 
wherever possible.  
All efforts will be made to obtain the cellular kinetics and PK samples at the scheduled 
nominal time relative to dosing. The time of the sample collection will be noted on the eCRF, 
sample labels, and requisition forms. If a scheduled blood sample collection cannot be 
completed for any reason, the missed sample time may be re-scheduled with agreement of 
the clinical investigator, subject, and sponsor. 
Cellular kinetics samples for ALLO-501A and PK samples for ALLO-647, fludarabine, and 
cyclophosphamide will be assayed using a validated analytical method in compliance with 
the selected vendor’s standard operating procedures (SOPs).  
The cellular kinetics and PK samples must be processed and shipped as indicated in the 
central laboratory manual provided to the investigative site to maintain sample integrity. Any 
deviations from the PK sample handling procedure (eg, sample collection and processing 
steps, interim storage or shipping conditions), including any actions taken, must be 
documented and reported to the sponsor. On a case-by-case basis, the sponsor may decide 
whether sample integrity has been compromised.  
As part of understanding the PK of the investigational product, samples may be used for 
evaluation of the bioanalytical method, as well as for other internal exploratory purposes. 
These data will not be included in the clinical study report (CSR). 
Additional instructions for sample collection, processing, storage, and shipping will be 
provided in the study laboratory manual. 
7.4 
Biomarker and Pharmacodynamic Assessments 
Biospecimens collected for pharmacodynamic and other biomarker assessments may include 
peripheral blood, body fluids, tumor tissues, and bone marrow aspirate, and may be used to 
analyze DNA, RNA, proteins, or metabolic biomarkers, for achieving planned biomarker 
objectives. Refer to the Schedule of Activities for sample collection time points and to the 
study laboratory manual for sample processing and shipping.  
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The following biospecimen types are planned to be collected in support of study objectives. 
Additional biospecimens collected over the course of subject disease management may be 
submitted for biomarker analyses.  
7.4.1 
Archival/De Novo Tumor Biopsies 
Lymph node tumor biospecimens from archival and de novo biopsies may be used to analyze 
candidate nucleic acid and protein biomarkers for their ability to identify those subjects who 
are most likely to benefit from treatment with the study drugs. Biomarkers may include, but 
are not limited to target expression, nucleic acid analyses, as well as cell types and 
constituents of the tumor microenvironment. De novo tumor biopsies obtained upon disease 
progression may be used to investigate acquired mechanisms of resistance and detection of 
ALLO-501A cells. Additional information on tissue collection procedures can be found in 
the Schedule of Activities and the study laboratory manual. 
7.4.2 
Peripheral Blood and Derivatives 
Peripheral blood and derivatives may be used to characterize cell phenotypes, measure 
soluble proteins, and analyze nucleic acids to support study objectives. Examples may 
include cytokines and immunophenotyping, with additional analyses may be warranted based 
on emerging data. 
Subjects may be evaluated for disease response by the site investigator at times indicated in 
the Schedule of Activities. Disease assessments will be evaluated per the revised IWG 
Response Criteria for Malignant Lymphoma (Cheson et al, 2014). Flow cytometric or 
cytogenetic studies will not be used to determine response. MRD may be assessed by 
molecular assay as exploratory measurement to define response and duration of response. 
7.5 
Immunogenicity 
Blood samples may be analyzed for the detection of anti-drug antibody (ADA) and 
neutralizing antibody (Nab) against ALLO-647, TALEN and ALLO-501A scFv. ADA and 
Nab samples will be analyzed using validated analytical methods in compliance with the 
vendor’s standard operating procedures and FDA/EMA guidelines, eg, ADA sample assay 
and analysis may follow a ECL approach of screening, confirmation, and titration. Only 
those samples tested to be positive for ADA may be further analyzed for Nab. 
Additional instructions for sample collection, processing, storage, and shipping are provided 
in the study laboratory manual.  
As part of understanding the immunogenicity of the investigational products, samples may be 
used for evaluation of the bioanalytical methods. These data may be used for internal 
exploratory purposes and may not be included in the CSR. The samples will be retained in 
accordance with local regulations and if not used within this timeframe, will be destroyed. 
7.6 
Gene Expression  
In order to identify changes in expression signatures potentially associated with ALLO-501A 
expansion, efficacy and/or persistence, a whole transcriptome analysis including, but not 
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limited to, the study subject’s baseline state, as well as expanding versus declining 
populations of CAR+ T-cells in peripheral blood and in tumor tissue may be performed and 
compared to  a) the infusion product’s expression, b) between subjects who respond vs non-
responders, and/or c)  in reference to the subject’s baseline.    
7.7 
Genomic Analyses 
During the manufacturing process, ALLO-501A undergoes both lentiviral integration of a 
foreign gene and TALEN®-mediated gene disruption. Although existing experience suggests 
that risks of T-cell transformation following a lentiviral insertion or gene disruption are low, 
there is still a theoretical potential that the modifications introduced in ALLO-501A could 
lead to cell transformation. If a secondary T-cell transformation occurs, genomic assays may 
be performed to assess the mechanism of the transformation. 
Blood and/ or tissue samples may be collected at the time specified in the Schedule of 
Activities, and when a safety signal is detected and archived until assay. For example, in case 
a secondary T-cell malignancy occurs, an attempt should be made to collect bone marrow 
(BM) samples, as well as blood. The initial BM sample should be collected as close as 
possible to the diagnosis of said secondary malignancy. Further BM samples should be 
collected at the next scheduled visits. 
Samples may be drawn and processed under the conditions described in the procedure 
manual, and subsequently cryopreserved at ≤–70°C until shipment to a third-party laboratory, 
where they may be processed and/or archived until a suitable assay is performed or until 
shipment to a central biorepository at the end of the study. 
7.8 
Banked Biospecimens  
Banked biospecimens, including serum/plasma, whole blood, bone marrow, and PBMC may 
be collected from subjects for other activities relating to the treatment response and disease 
under study, including assay bridging, sample stability, equivalency, etc. These specimens 
are not, by definition, pre-planned assessments described in the protocol. They would be 
handled in a manner that protects each subject’s privacy and confidentiality. Biospecimens 
will be assigned the subject’s study identification code, as generated in the eCRF. The data 
generated from assaying these biospecimens will also be indexed by this ID, and so not 
returned to the study subject. Biospecimens will be kept until destruction in facilities with 
access limited to authorized personnel, and biospecimen derived data will be stored on 
password protected computer systems. The key between the subject’s ID and the subject’s 
direct personally identifying information (eg, name, address) will only be held at the study 
site, and NOT by the Sponsor.  Unless a time limitation is required by local regulations or 
ethical requirements, biospecimens will be stored for many years (no time limit) to allow for 
research in the future, including research conducted during the lengthy drug development 
process and also post marketing research. Subjects may withdraw their consent for the use of 
their banked biospecimens at any time prior to the assay, by making a request to the 
investigator; in this case, any remaining biospecimens will be destroyed, but data already 
generated from the biospecimens will continue to be available to protect the integrity of 
existing analyses.  
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Unless prohibited by local regulations or ethics committee decision, a blood biospecimen 
(dipotassium edetic acid [ethylenediaminetetraacetic acid] [K2EDTA] whole blood collection 
optimized for a variety of assays) will be collected at the time specified in the Schedule of 
Activities for potential biomarker assays, e.g. known, novel, and complex fusion events, as 
well as other common alterations (substitutions, indels, and CNVs), etc, related to treatment 
and disease under study.   Similarly, the specimen may be used to assay for pathogens, either 
pre-existing and latent, or pathogens which appear following lymphodepletion. Such 
pathogens (eg, HHV6, HHV7, HTLV-1, etc.) may not be routinely clinically tested, 
depending on the standard of care at the site. 
Detailed collection, processing, storage, and shipment instructions are provided in the study 
laboratory manual. 
It is possible, though highly unlikely, that these biospecimens may result in commercially 
viable products, eg, an assay developed to detect a nucleic acid sequence identified in a study 
subject. Subjects will be advised in the informed consent document/subject information sheet 
that they will not be compensated in this event. 
7.9 
Patient Reported Outcomes 
Reducing mortality and morbidity is still the most important factor in clinical research. 
Nevertheless, issues such as reducing side effects, symptom relief and improving patients’ 
satisfaction have also become relevant parameters in the evaluation of medical strategies. 
Cancer treatments may produce adverse effects and diminish the quality of life (QoL) even 
when survival is extended. Progress in the acceptance of new cancer therapies is sometimes 
critically dependent on their QoL consequences. Health related QoL is a multidimensional 
concept, which represents the physiological, psychological and social influences of the 
disease and the therapeutic process from the patients’ perspective. It comprises 4 principal 
components: physical, psychological, social well-being, and daily-life functioning.  
The EQ-5D-5L is a generic patient questionnaire for assessing the overall health status of a 
patient. The EQ-5D-5L consists of a 5-dimension descriptive system including questions on 
mobility, selfcare, usual activities, pain/comfort, and anxiety/depression and a visual 
analogue scale (EQ VAS) which allows the respondent to record health on a vertical scale 
(eg, best health to worst health) thus allowing a quantitative measure of health outcome. 
Quality of life will also be assessed with the EORTC Quality of Life Questionnaire (QLQ-
C30) version 3. This is composed of multi-item and single scales. These include 5 functional 
scales (physical, role, emotional, social, and cognitive), 3 symptoms (fatigue, nausea and 
vomiting, and pain), and a global health status/QoL scale and 6 single items (dyspnea, 
insomnia, appetite loss, constipation, diarrhea and financial difficulties). All scales and single 
items meet the standards for reliability. The reliability and validity of the questionnaire is 
highly consistent across different language-cultural groups. 
EQ-5D-5L (PRO) and the QLQ-C30 (PRO) will be completed as outlined in the Schedule of 
Activities where possible. The study staff; however, cannot interpret any of the questions for 
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the subject. A subject may be exempt from completing the questionnaire if he or she is 
unable to read the questionnaire in one of the country languages available. 
8. ADVERSE EVENT REPORTING 
8.1 
Requirements 
Table 3 summarizes the requirements for recording safety events on the CRF and for 
reporting safety events to sponsor or designee per the study guidelines. These requirements 
are delineated for 3 types of events: (1) SAEs; (2) non-serious adverse events; and 
(3) exposure to the investigational product under study during pregnancy or breastfeeding.  
Table 3. Adverse Event Reporting 
Safety Event 
Recorded on the eCRF 
Reported on separate Form to 
Sponsor or Designee Within 
24 Hours of Awareness* 
SAE 
All 
All, use SAE/AESI report form 
Non-serious AE 
All 
None 
Adverse Event of Special Interest 
All 
All, use SAE/AESI report form 
Exposure to the investigational 
products under study during 
pregnancy or breastfeeding 
All (regardless of whether 
associated with an AE) 
Exposure during pregnancy, 
exposure via breastfeeding, 
(regardless of whether 
associated with an AE) 
* As per the reporting time period. 
All observed or volunteered events or suspected causal relationship to the investigational 
products will be reported as described in the following paragraphs. 
Events listed in Table 3 that require reporting to the sponsor or designee on the SAE/AESI 
Report Form within 24 hours of awareness of the event by the investigator are to be 
reported regardless of whether the event is determined by the investigator to be related 
to an investigational product under study. In particular, if the SAE is fatal or 
life-threatening, notification to the sponsor or designee must be made immediately, 
irrespective of the extent of available event information. This time frame also applies to 
additional new (follow-up) information on previously forwarded reports. In the rare situation 
that the investigator does not become immediately aware of the occurrence of an event, the 
investigator must report the event within 24 hours after learning of it and document the time 
of his/her first awareness of the event. Refer to the study safety reporting guidelines for more 
details on using the safety report forms to report SAEs, AESIs, or exposure to the 
investigational products under study during pregnancy or breastfeeding. 
For each event, the investigator must pursue and obtain adequate information both to 
determine the outcome and to assess whether it meets the criteria for classification as an SAE 
(see Section 8.2.4). In addition, the investigator may be requested by the sponsor or designee 
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to obtain specific follow-up information in an expedited fashion. This information is more 
detailed than that recorded on the eCRF. In general, this will include a description of the 
event in sufficient detail to allow for a complete medical assessment of the case and 
independent determination of possible causality. Any information relevant to the event, such 
as concomitant medications and illnesses, must be provided. In the case of a subject death, a 
summary of available autopsy findings must be submitted as soon as possible to the sponsor 
or designee. Any pertinent additional information must be reported on the SAE/AESI Report 
Form; additional source documents (eg, medical records, eCRF, laboratory data) are to be 
sent to the sponsor or designee ONLY upon request. 
As part of ongoing safety reviews conducted by the sponsor, any non-serious AE that is 
determined by the sponsor to be serious will be reported by the sponsor as an SAE. To assist 
in the determination of case seriousness, further information may be requested from the 
investigator to provide clarity and understanding of the event in the context of the clinical 
study. 
8.1.1 
Additional Details on Recording Adverse Events on the eCRF 
All events detailed in Table 3 will be recorded on the AE page(s) of the eCRF. It should be 
noted that the paper report form for reporting of SAE information to sponsor 
pharmacovigilance is not the same as the AE page of the eCRF. When reporting SAEs, the 
forms must be completed in a consistent manner. AEs should be recorded using concise 
medical terminology and the same SAE term should be used on both the eCRF and the paper 
report form for reporting of SAE information. 
8.1.2 
Eliciting Adverse Event Information 
The investigator is to record on the eCRF all directly observed AEs and all AEs 
spontaneously reported by the study subject. In addition, each study subject will be 
questioned about the occurrence of AEs in a non-leading manner. 
8.1.3 
Time Period for Collecting AE/AESI/SAE Information 
The time period for actively eliciting and collecting AEs, AESIs and SAEs for each subject 
begins from the time the subject provides informed consent (does not include prescreening 
consent) which is obtained before the subject’s participation in the study (ie, before receiving 
investigational products), through 60-month follow-up visit scheduled 
 after the 
initial dose of ALLO-501A according to the guidance below.   
All AEs will be collected through  months (
 days) after the last dose of ALLO-501A or 
until a subject begins a new anti-cancer therapy, whichever happens first.  After 
 
 AESIs and SAEs will be collected until 
, disease progression, or initiation 
of a new anti-cancer therapy, whichever happens first.  SAEs that are assessed as related to 
the IMP by the investigator should be collected and reported regardless of the time of 
occurrence (including beyond disease progression and initiation of new anti-cancer therapy).  
Events relevant for long-term follow-up (ie, the long term AESIs (Section 8.2.2) malignancy, 
hematological disorders, autoimmune disorders, neurological disorders, infections potentially 
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related to product) will be followed for a total of 5 years in this protocol and in a separate 
long term follow up protocol for a total of 15 years.    
For AEs that do not meet the definition of a SAE and which occur during the period from the 
time the screening informed consent is signed but prior to the subject receiving 
lymphodepletion, only those associated with protocol-related procedures should be reported. 
For subjects who are screen failures, the data collection period ends when screen failure 
status is determined. 
8.1.4 
Causality Assessment 
The investigator’s assessment of causality must be provided for all AEs (serious and 
non-serious); the investigator must record the causal relationship on the eCRF, and report 
such an assessment in accordance with the SAE reporting requirements, if applicable. An 
investigator’s causality assessment is the determination of whether there exists a reasonable 
possibility that the investigational products caused or contributed to an AE (ie, is there a 
reasonable possibility that the AE is related to the study treatment - No [unrelated] or Yes 
[related]). Generally, the facts (evidence) or arguments to suggest a causal relationship 
should be provided. If the investigator does not know whether the investigational product 
caused the event, then the event will be handled as “related to investigational product” for 
reporting purposes, as defined by the sponsor. If the investigator's causality assessment is 
“unknown but not related” to investigational product, this should be clearly documented on 
study records.  
In addition, if the investigator determines that an SAE is associated with study procedures, 
the investigator must record this causal relationship in the source documents and eCRF, and 
report such an assessment in the dedicated section of the SAE Report Form and in 
accordance with the SAE reporting requirements. 
8.1.5 
Sponsor’s Reporting Requirements to Regulatory Authorities 
AE reporting, including suspected unexpected serious adverse reactions, will be carried out 
in accordance with applicable ICH, EU, and country specific guidelines.  In the US, the FDA 
will be notified according to guidelines for expedited safety reporting in accordance with 21 
CFR 312.32 c(1) and Guidance for Industry and Investigators Safety Reporting Requirements 
for INDs and BA/BE Studies Dec 2012. 
The reference safety information for ALLO-501A and ALLO-647 will be the Investigator 
Brochure for each respective investigational product. 
8.2 
Definitions 
8.2.1 
Adverse Events 
An adverse event or experience is defined as any symptom, sign, illness, abnormal test 
finding, or untoward experience that develops or worsens during the course of the study, 
whether or not the event is considered related to the investigational product(s). 
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When a diagnosis is possible, it is preferable to record it, rather than a series of signs or 
symptoms relating to the diagnosis, on the case report form. 
Examples of adverse events include:  
• 
A worsening, excluding minor fluctuations, in the nature, severity, frequency, or 
duration of a pre-existing condition;  
• 
Development of an intercurrent illness during the study;  
• 
Development of symptoms which may or may not be related to the use of a 
concomitant medication or study drug;  
• 
Injury or accidents: if a medical condition is known to have caused the injury or 
accident, the medical condition and the accident should be reported as 2 separate 
medical events (eg, for a fall secondary to dizziness, both “dizziness” and “fall” 
should be recorded separately). 
Adverse events are detected in 2 ways:  
• 
Clinical: symptoms reported by the subject or signs detected on examination;  
• 
Ancillary Tests: clinically significant abnormalities of vital signs, ECG, laboratory 
tests, and other diagnostic procedures.  
An adverse event does not include: 
• 
Medical or surgical procedures (eg, surgery, endoscopy, tooth extraction, 
transfusion). The condition that leads to the procedure is an adverse event; 
• 
Pre-existing diseases or conditions present or detected prior to the start of study drug 
administration that do not worsen; 
• 
Situations where an untoward medical event has not occurred (eg, hospitalization for 
elective surgery, social and/or convenience admissions); 
• 
Overdose of either study drug or concomitant medication without any signs or 
symptoms. 
• 
Hospitalizations for study treatment infusions or precautionary measures per 
institutional policy. 
Additionally, AEs may include signs and symptoms resulting from: 
• 
Drug overdose; 
• 
Drug withdrawal; 
• 
Drug misuse;  
• 
Drug interactions; 
• 
Extravasation; 
• 
Exposure during pregnancy (EDP); 
• 
Exposure via breastfeeding; 
• 
Medication error. 
8.2.2 
Adverse Events of Special Interest 
An AE of special interest (AESI) is a noteworthy event for the particular product or class of 
products that a sponsor may wish to monitor carefully. It could be serious or non-serious AE 
which may require further investigation to characterize and understand it.  
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The following events, regardless of causality to ALLO-501A and ALLO-647, are considered 
as AESIs (see Section 8.1.3): 
• Grade ≥3 CRS  
• Grade ≥3 Neurologic toxicity 
• Grade ≥3 Infection 
• GvHD 
• Autoimmune disorders  
• Secondary malignancies 
• Suspected transmission of an infectious agents by a medicinal product (STIAMP) 
The following events regardless of causality to ALLO-501A and ALLO-647 are considered 
as long-term AESI (see Section 8.1.3 and Appendix 11): 
• Chronic GvHD 
• New incidence or exacerbation of a pre-existing rheumatologic or Autoimmune 
disorders  
• New incidence or exacerbation of a pre-existing neurologic disorder 
• Secondary malignancies and/or haematological disorders 
• New incidence of infection (potentially product-related) 
All AESIs should be reported within 24 hours of staff becoming aware of them and handled 
the same as SAEs. 
8.2.3 
Abnormal Test Findings 
Abnormal objective test findings should be recorded as AEs when any of the following 
conditions are met:  
• 
Test result is associated with accompanying symptoms; and/or 
• 
Test result requires additional diagnostic testing or medical/surgical intervention; 
and/or 
• 
Test result leads to a change in study dosing (outside of any protocol specified dose 
adjustments) or discontinuation from the study, significant additional concomitant 
drug treatment, or other therapy; and/or 
• 
Test result is considered to be an AE by the investigator or sponsor. 
Merely repeating an abnormal test, in the absence of any of the above conditions, does not 
constitute an AE. Any abnormal test result that is determined to be an error does not require 
recording as an AE. 
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8.2.4 
Serious Adverse Events 
A serious adverse event is any untoward medical occurrence at any dose that: 
• 
Results in death; 
• 
Is life-threatening (immediate risk of death); 
• 
Requires inpatient hospitalization or prolongation of existing hospitalization; 
• 
Results in persistent or significant disability/incapacity (substantial disruption of the 
ability to conduct normal life functions); 
• 
Results in congenital anomaly/birth defect. 
• 
Is considered an important medical event. 
Medical and scientific judgment is exercised in determining whether an event is an important 
medical event. An important medical event may not be immediately life-threatening and/or 
result in death or hospitalization. However, if it is determined that the event may jeopardize 
the subject or may require intervention to prevent one of the other AE outcomes, the 
important medical event should be reported as serious. 
Examples of such events are intensive treatment in an emergency room or at home for 
allergic bronchospasm; blood dyscrasias or convulsions that do not result in hospitalization; 
or development of drug dependency or drug abuse. 
Events that require an escalation of care when the subject is already hospitalized should be 
recorded as an SAE, eg, movement from routine care in the hospital to the ICU or if the event 
resulted in a prolongation of the existing planned hospitalization. 
8.2.5 
Hospitalization 
Hospitalization is defined as any initial admission (even less than 24 hours) in a hospital or 
equivalent healthcare facility, or any prolongation of an existing admission. Admission also 
includes transfer within the hospital to an acute/intensive care unit (eg, from the psychiatric 
wing to a medical floor, medical floor to a coronary care unit, or neurological floor to a 
tuberculosis unit). An emergency room visit does not necessarily constitute a hospitalization; 
however, the event leading to the emergency room visit is assessed for medical importance. 
Hospitalization does not include the following: 
• 
Rehabilitation facilities; 
• 
Hospice facilities; 
• 
Respite care (eg, caregiver relief); 
• 
Skilled nursing facilities; 
• 
Nursing homes; 
• 
Same-day surgeries (as outpatient/same-day/ambulatory procedures). 
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Hospitalization or prolongation of hospitalization in the absence of a precipitating clinical 
AE is not in itself an SAE. Examples include:  
• 
Admission for treatment of a preexisting condition not associated with the 
development of a new AE or with a worsening of the preexisting condition (eg, for 
workup of a persistent pretreatment laboratory abnormality); 
• 
Social admission (eg, subject has no place to sleep); 
• 
Administrative admission (eg, for yearly physical examination); 
• 
Protocol specified admission during a study (eg, for a procedure required by the study 
protocol); 
• 
Optional admission not associated with a precipitating clinical AE (eg, for elective 
cosmetic surgery); 
• 
Hospitalization for observation without a medical AE; 
• 
Preplanned treatments or surgical procedures. These should be noted in the baseline 
documentation for the entire protocol and/or for the individual subject; 
• 
Admission exclusively for the administration of blood products. 
Diagnostic and therapeutic noninvasive and invasive procedures, such as surgery, should not 
be reported as SAEs. However, the medical condition for which the procedure was 
performed should be reported if it meets the definition of an SAE. For example, an acute 
appendicitis that begins during the reporting period should be reported if the SAE 
requirements are met, and the resulting appendectomy should be recorded as treatment of the 
AE. 
8.2.6 
Disease Progression as an Adverse Event 
It is anticipated that a proportion of subjects will experience disease progression. Disease 
progression assessed by measurement of malignant lesions on radiographs or other methods 
but with no worsening of signs and symptoms should not be reported as AEs. 
Hospitalization due to signs and symptoms of disease progression should not be reported as 
an SAE.  
Progression of the malignancy under study (including signs and symptoms of progression) 
should not be reported as an SAE unless the outcome is fatal within the active collection 
period (see Section 8.1.3). A death attributed to disease progression of the underlying 
lymphoma should be recorded with the preferred term of B-cell lymphoma, with NCI 
CTCAE Grade 5 (see Severity Assessment in Section 8.3) and must be reported immediately 
to the sponsor. 
8.3 
Severity Assessment 
Severity will be graded by the NCI CTCAE version 5.0 or Table 4 below if not covered by 
CTCAE. CRS will be assessed per ASTCT 2019 (Table 1) and GvHD will be assessed as per 
Appendix 3 and Appendix 4. 
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Table 4. Adverse Event Severity Assessment 
Grade 
Clinical Description of Severity 
1 
Mild asymptomatic or mild symptoms; clinical or diagnostic observations only; 
intervention not indicated 
2 
Moderate; minimal, local or noninvasive intervention indicated; limiting age-
appropriate instrumental activities of daily living (such as preparing meals, 
shopping for groceries or clothes, using the telephone, managing money, etc.) 
3 
Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; limiting 
self-care activities of daily living (such as bathing, dressing and undressing, 
feeding self, using the toilet, taking medications, and not bedridden) 
4 
Life-threatening consequences; urgent intervention indicated 
5 
Death related to AE 
Note the distinction between the severity and the seriousness of an AE. A severe event is not 
necessarily an SAE. For example, a headache may be severe (interferes significantly with the 
subject’s usual function) but would not be classified as serious unless it met one of the 
criteria for SAEs listed in Table 4. 
8.4 
Special Situations 
8.4.1 
Potential Cases of Drug-Induced Liver Injury 
Humans exposed to a drug who show no sign of liver injury (as determined by elevations in 
transaminases) are termed “tolerators,” while those who show transient liver injury, but adapt 
are termed “adaptors.” In some subjects, transaminase elevations are a harbinger of a more 
serious potential outcome. These subjects fail to adapt and therefore are "susceptible" to 
progressive and serious liver injury, commonly referred to as drug-induced liver injury 
(DILI). Subjects who experience a transaminase elevation above 3 times the upper limit of 
normal (× ULN) should be monitored more frequently to determine if they are an “adaptor” 
or are “susceptible.” 
In the majority of DILI cases, elevations in AST and/or ALT precede total bilirubin (TBili) 
elevations (>2 × ULN) by several days or weeks. The increase in TBili typically occurs while 
AST/ALT is/are still elevated above 3 × ULN (ie, AST/ALT and TBili values will be 
elevated within the same laboratory sample). In rare instances, by the time TBili elevations 
are detected, AST/ALT values might have decreased. This occurrence is still regarded as a 
potential DILI. Therefore, abnormal elevations in either AST OR ALT in addition to TBili 
that meet the criteria outlined below are considered potential DILI (assessed per Hy’s law 
criteria) cases and should always be considered important medical events, even before all 
other possible causes of liver injury have been excluded. 
The threshold of laboratory abnormalities for a potential DILI case depends on the subject’s 
individual baseline values and underlying conditions. Subjects who present with the 
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following laboratory abnormalities should be evaluated further as potential DILI (Hy’s law) 
cases to definitively determine the etiology of the abnormal laboratory values: 
• Subjects with AST/ALT and TBili baseline values within the normal range who 
subsequently present with AST OR ALT values >3 × ULN AND a TBili value 
>2 × ULN with no evidence of hemolysis and an alkaline phosphatase value 
<2 × ULN or not available; 
• For subjects with baseline AST OR ALT OR TBili values above the ULN, the 
following threshold values are used in the definition mentioned above, as needed, 
depending on which values are above the ULN at baseline: 
Preexisting AST or ALT baseline values above the normal range: AST or ALT values 
>2 times the baseline values AND >3 × ULN; or >8 × ULN (whichever is 
smaller). 
Preexisting values of TBili above the normal range: TBili level increased from 
baseline value by an amount of at least 1 × ULN or if the value reaches 
>3 × ULN (whichever is smaller). 
Rises in AST/ALT and TBili separated by more than a few weeks should be assessed 
individually based on clinical judgment; any case where uncertainty remains as to whether it 
represents a potential Hy’s law case should be reviewed with the sponsor. 
The subject should return to the investigator site and be evaluated as soon as possible, 
preferably within 48 hours from awareness of the abnormal results. This evaluation should 
include laboratory tests, detailed history, and physical assessment. 
In addition to repeating measurements of AST and ALT and TBili, laboratory tests should 
include albumin, creatine kinase, direct and indirect bilirubin, gamma-glutamyl transferase, 
prothrombin time/international normalized ratio, total bile acids, alkaline phosphatase and 
acetaminophen drug and/or protein adduct levels. Consideration should also be given to 
drawing a separate tube of clotted blood and an anticoagulated tube of blood for further 
testing, as needed, for further contemporaneous analyses at the time of the recognized initial 
abnormalities to determine etiology. A detailed history, including relevant information, such 
as review of ethanol, acetaminophen (either by itself or as a co-formulated product in 
prescription or over-the-counter medications), recreational drug, supplement (herbal) use and 
consumption, family history, sexual history, travel history, history of contact with a 
jaundiced person, surgery, blood transfusion, history of liver or allergic disease, and potential 
occupational exposure to chemicals, should be collected. Further testing for acute hepatitis A, 
B, C, D, and E infection and liver imaging (eg, biliary tract) may be warranted.  
All cases demonstrated on repeat testing as meeting the laboratory criteria of AST/ALT and 
TBili elevation defined above should be considered potential DILI (Hy’s law) cases if no 
other reason for the LFT abnormalities has yet been found. Such potential DILI (Hy’s law) 
cases are to be reported as SAEs, irrespective of availability of all the results of the 
investigations performed to determine etiology of the LFT abnormalities.  
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A potential DILI (Hy’s law) case becomes a confirmed case only after all results of 
reasonable investigations have been received and have excluded an alternative etiology. 
8.4.2 
Exposure to the Investigational Product During Pregnancy or Breastfeeding 
Exposure to the investigational product under study during pregnancy are reportable to the 
sponsor or designee within 24 hours of investigator awareness. 
For both unapproved/unlicensed products and for marketed products, an EDP occurs if: 
• 
A female becomes, or is found to be, pregnant either while receiving or having been 
exposed (eg, because of treatment or environmental exposure) to the investigational 
product; or the female becomes or is found to be pregnant after discontinuing and/or 
being exposed to the investigational product; 
• 
An example of environmental exposure would be a case involving direct contact with 
an Allogene product in a pregnant woman (eg, a nurse reports that she is pregnant and 
has been exposed to chemotherapeutic products). 
• 
A male has been exposed (eg, because of treatment or environmental exposure) to the 
investigational product prior to or around the time of conception and/or is exposed 
during his partner’s pregnancy. 
If a subject or subject’s partner becomes or is found to be pregnant during the subject’s 
treatment with the investigational product, the investigator must report this information to the 
sponsor and/or designee following the safety reporting guidelines provided to the 
investigational site.  
In addition, the investigator must submit information regarding environmental exposure to an 
Allogene product in a pregnant woman (eg, a subject reports that she is pregnant and has 
been exposed to a cytotoxic product by inhalation or spillage). This must be done irrespective 
of whether an AE has occurred and Allogene will be notified within 24 hours of awareness of 
the exposure. The information submitted should include the anticipated date of delivery (see 
below for information related to termination of pregnancy). 
Follow-up is conducted to obtain general information on the pregnancy and its outcome for 
all EDP reports with an unknown outcome. The investigator will follow the pregnancy until 
completion (or until pregnancy termination) and notify the sponsor or designee of the 
outcome as a follow-up to the initial EDP supplemental form. In the case of a live birth, the 
structural integrity of the neonate can be assessed at the time of birth. In the event of a 
termination, the reason(s) for termination should be specified and, if clinically possible, the 
structural integrity of the terminated fetus should be assessed by gross visual inspection 
(unless pre-procedure test findings are conclusive for a congenital anomaly and the findings 
are reported). 
Additional information about pregnancy outcomes that are reported to the sponsor or 
designee follows:  
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• 
Spontaneous abortion includes miscarriage and missed abortion; 
• 
Neonatal deaths that occur within 1 month of birth should be reported, without regard 
to causality. In addition, infant deaths after 1 month should be reported when the 
investigator assesses the infant death as related or possibly related to exposure to the 
investigational product.  
Additional information regarding the EDP may be requested by the sponsor. Further 
follow-up of birth outcomes will be handled on a case-by-case basis (eg, follow-up on 
preterm infants to identify developmental delays). The investigator will provide the subject 
or the subject’s partner with the Pregnancy Informed Consent Form. The investigator must 
document the consent statement in the trial source documents for the subject or the subject’s 
partner.  
8.5 
Data Monitoring Committee/Data Safety Monitoring Board 
An independent data and safety monitoring board (DSMB) will be chartered to review 
accumulating safety and efficacy data throughout the study.   
The DSMB will review SAE information and enrollment pausing criteria after 
 have been randomized and have had the opportunity to be followed for 
 
after the first dose of lymphodepletion.   
During these periodic reviews and formal interim analyses, DSMB will also review all 
available study conduct data (e.g. accrual), and trial progress data. The DSMB may request 
additional safety data or recommend modifications of the study conduct, including the 
accrual of additional subjects or termination of the trial. 
At the time of second interim analysis the DSMB will also provide a recommendation such 
as stopping treatment for futility or to implement the adaptive sample size adjustment.  The 
DSMB may request additional reviews as needed. 
The sponsor may request additional reviews by the DSMB, or the DSMB may request 
additional reviews to the sponsor if safety or feasibility concerns are identified. The DSMB 
may make recommendations regarding study conduct of the study if safety or feasibility 
concerns are identified.  Data submitted to the DSMB may be monitored or unmonitored to 
facilitate and ensure timely DSMB review. The scope and remit of the DSMB will be 
described in a DSMB Charter. 
Sponsor access to the ongoing trial data will be controlled and described in the DSMB 
Charter and Trial Integrity Document. 
9. STATISTICAL METHODS 
Detailed methodology for summary and statistical analyses of the data collected in this study 
are outlined here and further detailed in statistical analysis plans (SAPs) separately. 
The data will be summarized with respect to demographic and baseline characteristics, 
efficacy observations and measurements, safety observations and measurements, PK and 
biomarker measurements.  
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9.1 
Analysis Sets  
1. Intent-to-Treat Analysis Set (All Randomized): The intent-to-treat (ITT) analysis set 
will consist of all randomized subjects. Unless otherwise specified, the ITT analysis 
set will be used as the primary analysis set for all efficacy analyses. Subjects will be 
analysed based on randomized treatment assignment, regardless of treatment 
received.   
2. Modified Intent-to-Treat Analysis Set: The modified intent-to-treat (mITT) analysis 
set includes all randomized subjects who received ALLO-501A. The mITT analysis 
set will be used for sensitivity analyses of efficacy endpoints. Subjects will be 
summarized according to the actual treatment received.   
3. Safety Analysis Set: The safety analysis set includes all randomized subjects who 
receive at least one (partial or complete) dose of ALLO-647 or ALLO-501A.  This 
analysis set will be used for analyses of safety.  Subjects will be summarized 
according to the actual treatment received.  Separate safety analysis sets will be 
defined for ALLO-647 and ALLO-501A with details in the SAP. 
4. PK Analysis Sets:  Separate PK analysis population will be defined for ALLO-647 
and ALLO-501A.  
(a) The PK parameter analysis population is defined as all randomized 
subjects treated who do not have protocol deviations influencing PK 
assessment and have sufficient information to estimate at least 1 of the PK 
parameters of interest. 
(b) The PK concentration population is defined as all randomized subjects 
who are treated and have at least 1 analyte concentration at baseline and 
post baseline. 
5. Pharmacodynamic/Biomarker Analysis Set: The pharmacodynamic/biomarker 
analysis population is defined as all randomized subjects with at least 1 of the 
pharmacodynamic/biomarkers evaluated at pre and/or post-dose. 
6. Immunogenicity Analysis Set: The immunogenicity analysis set includes all 
randomized subjects who receive at least 1 dose of study treatment and have at least 
1 valid result for the ADA testing. 
9.2 
Sample Size Determination 
A target of approximately 70 subjects may be randomized 1:1 to FC and FCA arm in the 
study. This study is designed with an adaptive sample size re-adjustment. 
  
A PFS hazard ratio (FCA/FC) of 0.40 is hypothesized in the intent-to-treat (ITT; all 
randomized) analysis set.  Assuming an exponential distribution for PFS and a median PFS 
of 2 months in the FC arm, this implies a 250% relative improvement in PFS and under the 
assumption of an exponentially distributed PFS time, corresponds to median PFS of 2 versus 
5 months (CRISPR Therapeutics 2021; Precision Biosciences 2020; Neelapu et al, 2017, Jain  
et al, 2021, and Locke et al, 2019).  The primary analysis is planned when 50 PFS have been 
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observed; the study has been sized to achieve 90% power at the 1-sided 2.5% significance 
level to detect a 250% improvement in median PFS time.  
 
 
  
 
 
 
 
The secondary endpoint ORR will be tested hierarchically using stepwise method after 
primary endpoint of PFS is statistically significant.  
An independent DSMB will be chartered to conduct interim analyses and provide 
recommendations on study conduct.  The DSMB will review SAE information and 
enrollment pausing criteria
 have been randomized and have 
had the opportunity to be followed for 30 days after the first dose of lymphodepletion.  
Additionally, the DSMB chair will receive all expedited safety reports at the time of 
regulatory submission and may request additional safety data at any time. The DSMB will 
review data at 2 formal interim analyses.  The first interim analysis will be for safety and 
feasibility and will occur after 15 subjects have been randomized and have had the 
opportunity to be followed for 2 months after randomization.  The second interim analysis 
will occur when 25 PFS events have been observed, at which time the DSMB will evaluate 
safety, feasibility, early stopping for futility, and the adaptive sample size re-adjustment.  
Evaluation of early efficacy will not be assessed at the time of the 2nd interim analysis.  The 
study will have an overall alpha level of 2.5% with 1-sided testing.  The futility interim 
analysis will use an O’Brien-Fleming spending rule.  Finally, if the event goal of 50 PFS 
events is unattainable within 1 year of the projected analysis timing, the DSMB may 
recommend conducting the primary analysis prior to the observation of 50 events at event 
target determined by the DSMB.  Under the design assumptions, this will preserve 80% 
power and enable a conclusion from the study to be reached.  A schematic of the study is 
provided in Figure 2.  The DSMB may recommend stopping the study for futility if the 
futility criteria are met.  
In the event the DSMB makes recommendations on changes to the trial conduct, Allogene, or 
the DSMB on behalf of Allogene, will discuss these recommendations with the agency prior 
to their implementation.   
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Adaptive Sample Size Re-adjustment 
The adaptive sample size re-adjustment will be evaluated at the time of the 25-PFS event 
interim analysis.  At this interim analysis time, the conditional power for the primary analysis 
will be calculated under the observed interim analysis hazard ratio.  The conditional power 
will be considered in the ‘promising zone’ if the conditional power is ≥ 50% or < 90%. 
 
 
If the conditional power falls outside the promising zone, either < 50% or ≥ 90%, study will 
be terminated due to futility or no change to the sample size will be made. As shown in Chen 
, 2004, and Mehta , 2011, this adaptive strategy, defined by pre-specification of a promising 
zone with a lower limit of conditional power of at least 50% and the pre-specification of a 
maximum number of events for the adjustment can be analyzed with unadjusted testing 
methods while preserving the overall type I error at 2.5%.   The independent statistician, in 
conjunction with the DSMB, will evaluate the interim analysis and implement any adaptive 
sample size re-estimation in accordance with this method pre-specified and further 
documented in DSMB charter. 
Access to Individual Subject Treatment Assignments 
In this randomized study, investigators will be aware of treatment received. Data handling 
procedures for the study will be devised to reduce potential sources of bias and maintain the 
validity and credibility of the study. These procedures will be outlined in the SAP, DSMB 
charter, and Trial Integrity Document.  
9.3 
Statistical Methods and Properties 
9.3.1 
Study Endpoints  
All corresponding endpoints to study objectives are listed in Section 2.2. 
9.3.1.1 
Primary Endpoints 
The primary efficacy endpoint for the evaluation of ALLO-647 efficacy will be PFS between 
treatment arms, defined as the time from randomization to disease progression, or relapse per 
the Lugano classification criteria (Cheson et al, 2014),  as assessed by IRC,  or death. 
Subjects not meeting the criteria for progression by the analysis data cutoff date will be 
censored at their last evaluable disease assessment date.  Subjects who receive new anti-
cancer therapy  in the absence of documented disease progression will have PFS censored at 
the last evaluable disease assessment prior to the new anti-cancer therapy. 
The primary analysis for the evaluation of ALLO-647 will be conducted when 50 PFS events 
have been observed. The details of the primary analysis plan will be provided in the study 
SAP.  
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9.3.1.2 
Secondary Efficacy Endpoints 
Objective response rate (ORR): defined as assessment of CR or PR, assessed using the 
Lugano classification criteria 2014; Cheson et al, 2014) by IRC at any time up through 
commencement of new anti-cancer therapy or withdrawal of consent.   Secondary analyses 
will use disease assessments per the investigator. 
EFS defined as the time from randomization to disease progression or relapse per the Lugano 
classification criteria 2014 as assessed by IRC,  death, or commencement of a new anti-
cancer therapy.  
Duration of response (DOR): DOR for subjects who experience a CR or PR is defined as the 
date of their first response to the date of disease progression per Lugano classification criteria 
2014 (Cheson et al, 2014) as assessed by the IRC or death regardless of cause, whichever 
happens earlier.  For subjects who receive new anti-cancer therapy with no documented 
disease progression, duration of response will be censored at the last evaluable disease 
assessment prior to the new anti-cancer therapy.  Secondary analyses will use disease 
assessments per the investigator. 
Best overall response (BOR): BOR is defined as the best response (CR, PR, SD, PD) by IRC 
at any time up through commencement of new anti-cancer therapy or withdrawal of consent.  
Secondary analyses will use disease assessments per the investigator. 
Time to response (TTR): TTR is defined as the time from randomization date to the date of 
first CR or PR as assessed by the IRC per the Lugano classification criteria 2014 (Cheson et 
al, 2014).  Secondary analyses will use disease assessments per the investigator.  
Overall survival: OS is defined as the time from randomization to the date of death. Subjects 
who have not died by the analysis data cutoff date will be censored at their last contact date 
or the data cut-off date, if confirmed to be alive after the data cut-off date.  
9.3.2 
Efficacy Analysis  
9.3.2.1 
 Primary Efficacy Endpoint 
The primary analysis of PFS between treatment arms will be conducted using a stratified 
(randomization stratification factors) log rank test. KM curves will be presented, and KM 
estimates and 2-sided 95% confidence intervals will be calculated for event time quartiles, 
event-free rate at 3-month intervals, and for the difference in event-free rates between 
treatment arms at those times. Additionally, stratified (randomization stratification factors) 
Cox regression model will be used to estimate the relative PFS hazard ratio (FCA/FC) along 
with 2-sided 95% confidence intervals. The primary analysis is based on ITT population.  
Sensitivity analyses of the primary efficacy endpoint will be conducted in a similar fashion: 
1. Based on mITT population 
2. PFS based on investigator disease assessments 
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3. Unstratified COX regression analysis  
Summaries of off-schedule disease assessments by treatment arm will be provided.  
Sensitivity analyses to address ascertainment time bias will be provided in the SAP. 
9.3.2.2 
Analysis of Secondary Efficacy Endpoint 
After the primary endpoint showed statistical significance, the secondary efficacy endpoint 
ORR per IRC assessment will be tested hierarchically using stepwise method.  The test will 
be performed with the Cochran Mantel Haenszel (CMH) test stratified by the randomization 
stratification factor. 
Analysis of all secondary efficacy endpoints will be performed by treatment arms. 
ORR: The ORR based on IRC assessment and on investigator assessment between treatment 
arms will be compared using exact binomial test. The Clopper Pearson exact interval 95% CI 
for rate in each treatment arm will be provided. The Wilson confidence interval will be 
provided as sensitivity analysis. CMH test stratified by randomization stratification factor 
will be used to compare the proportion difference of ORR between treatment arm along with 
95% C.I.  
DOR: DOR for subjects who experience a CR or PR will be summarized. For subjects who 
have a CR or PR as assessed by the IRC and assessed by investigator, Kaplan-Meier (KM) 
estimates and 2-sided 95% CIs will be generated for DOR.     
BOR: The percentage of subjects with each response category (CR, PR, SD, PD) as their 
BOR will be summarized based on IRC assessment and on investigator assessment.  Two-
sided 95% confidence intervals for the proportion of subjects with BOR of CR and of PR will 
be provided. The Clopper Pearson exact interval 95% CI for rate in each treatment arm will 
be provided. The Wilson confidence interval will be provided as sensitivity analysis. CMH 
test stratified by randomization stratification factor will be used to compare the proportion 
difference of ORR between treatment arm along with 95% C.I. 
EFS, and OS: The KM method will be used to estimate  EFS, and OS proportions, 95% CIs, 
and summary statistics at landmark times after randomization. The stratified log rank test will 
compare EFS or OS rate at landmark times. The number of subjects who have progressed 
and/or have ongoing responses will be summarized along with KM plots. Analysis will be 
based on IRC assessment and investigator assessment. In addition, the stratified Cox 
regression model will be used to estimate the HR between treatment arm (FCA vs FC) along 
with 95%CI.  
TTR will be summarized between treatment arm (FCA vs FC alone) for subjects who 
responded to treatment. 
Sensitivity analyses of secondary endpoints will be performed in a similar fashion to the 
sensitivity analyses of primary endpoint and will be detailed in SAP. 
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Further details and all sensitivity analyses for secondary efficacy endpoints, including their 
detailed definitions and estimands will be provided in the SAP. 
 
 
 
 
9.3.3 
  Safety Analysis 
Summaries and analyses of safety parameters will include all subjects in the safety analysis 
set and will be conducted by treatment arms. 
9.3.3.1 
Adverse Events 
AEs will be graded by the investigator according to the CTCAE version 5.0 and coded using 
MedDRA. CRS will be graded using ASTCT; however, as per ASTCT end-organ damage 
will be graded using CTCAE. Data will be collected to allow grading of Grade ≥3 events of 
neurotoxicity and ICANS using the ASTCT definition. AE data will be analyzed using the 
principle of treatment emergence. The treatment-emergent period will be defined as the 
period of time from the first dose date of lymphodepletion (fludarabine, cyclophosphamide, 
or ALLO-647 and/ or ALLO-501A) up to the end of study, death or the date of initiation of 
another anti-cancer investigational agent, whichever occurs first. Adverse event data will be 
reported in listings. Summaries of adverse event by mapped terms, appropriate thesaurus 
level, toxicity grade, and seriousness and relationship to study treatment will be presented, as 
well as summaries of adverse events leading to death and premature withdrawal from study. 
The number and percentage of subjects who experienced any AE, SAE, treatment related AE, 
and treatment related SAE will be summarized according to worst toxicity grades. Treatment 
emergent adverse events of special interest (as defined in Section 8.2.2) will be summarized 
accordingly. In addition, the grading of neurotoxicity AEs will be summarized based on 
CTCAE criteria. The summaries will present AEs on the entire study period. Adverse events 
will be summarized by treatment arm. 
The severity of acute GvHD and CRS will be assessed according to the modified grading 
described in Appendix 3 and Appendix 5, respectively. 
9.3.3.2 
Laboratory Test Abnormalities 
The number and percentage of subjects who experienced laboratory test abnormalities will be 
summarized according to worst toxicity grade (as graded by NCI CTCAE version 5.0) 
observed for each laboratory assay. The analyses will summarize laboratory tests as 
characterized by type, frequency, severity and timing. For laboratory tests without CTCAE 
grade definitions, results will be categorized as normal, abnormal, or not done. Laboratory 
test abnormality will be summarized by the treatment arm. 
9.3.3.3 
Electrocardiogram 
The analysis of ECG results will be based on subjects in the safety analysis set with baseline 
and on-treatment ECG data.  
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ECG measurements will be used for statistical analysis and all data presentations. Any data 
obtained from ECGs repeated for safety reasons after the nominal timepoints will not be 
averaged along with the preceding measurement. The percentage of subjects in each 
treatment group with new, abnormal, and clinically significant ECG findings will be 
summarized by study visit. 
QT intervals will be corrected for heart rate (QTc) using standard correction factors 
(ie, Fridericia’s [default correction], Bazett’s). Data will be summarized and listed for QT, 
HR, QRS, QTcF, and by dose and the treatment arm. Individual QT intervals will be listed by 
time and dose. 
9.3.4 
Analysis of Pharmacokinetics and Pharmacodynamics  
9.3.4.1 
ALLO-501A 
The ALLO-501A PK analysis set will be defined as subjects having received at least 1 dose 
of ALLO-501A and 1 measurable post-dose PK concentration. Descriptive statistics (count 
[N], arithmetic mean, geometric mean, standard deviation, minimum, median, maximum, and 
coefficient of variation [CV]) will be performed per dose group (Phase 1) and by treatment 
arms  on ALLO-501A vector copy number (VCN) in blood at each measurement time. 
Graphical displays of mean values will also be presented for PK analysis set. Derived 
parameters (AUC, Cmax, etc.) will also be computed. 
A model-based PK analysis will also be performed using the PK analysis set and will be 
described in a separate analysis plan. The PK/pharmacodynamic relationship between 
circulating ALLO-501A and relevant activity or safety measurements may also be 
investigated.  
9.3.4.2 
ALLO-647 
The ALLO-647 PK analysis set will be defined as the subjects having received at least 1 dose 
of ALLO-647 and 1 measurable post-dose PK concentration.  
Descriptive statistics (N, arithmetic mean, geometric mean, standard deviation, min, median, 
max, CV) will be performed on ALLO-647 plasma concentrations at each timepoint. 
Graphical displays of mean values will also be presented. PK data collected will be used in a 
population PK modeling approach to estimate individual PK parameters such as clearance, 
half-life, etc. Population PK will be used to estimate individual exposure parameters such as 
Cmax and AUC. 
9.3.4.3 
Analysis of Pharmacodynamics  
9.3.4.3.1 
Analysis to characterize depth and duration of lymphodepletion 
Descriptive summary of minimum of ALC after
 
 will be 
summarized by dose groups (Phase 1) and treatment arms (Phase 2). The time to recovery of 
TBNK cell burden analysis will be performed for subjects (in both the Phase 1 and Phase 2 
portions of the study), comparing values before and after ALLO-647 administration (after 
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The investigator(s) will notify Allogene or its agents immediately of any regulatory 
inspection notification in relation to the study. Furthermore, the investigator will cooperate 
with Allogene or its agents to prepare the investigator site for the inspection and will allow 
Allogene or its agent, whenever feasible, to be present during the inspection. The investigator 
site and investigator will promptly resolve any discrepancies that are identified between the 
study data and the subject's medical records. The investigator will promptly provide copies of 
the inspection findings to Allogene or its agent. Before response submission to the regulatory 
authorities, the investigator will provide Allogene or its agents with an opportunity to review 
and comment on responses to any such findings. 
It is important that the investigator(s) and their relevant personnel are available during the 
monitoring visits and possible audits or inspections and that sufficient time is devoted to the 
process. 
11. DATA HANDLING AND RECORD KEEPING 
11.1 
Case Report Forms/Electronic Data Record 
The study will be using an electronic data capture system. All electronic case report forms 
will be designed and provided electronically to the site by Allogene (or designee) and 
electronic data capture system vendor. All case report forms are to be completely filled out 
and reviewed and signed by the investigator or sub-investigators listed on the Form FDA 
1572 and/or other appropriate local health authority documents. Every effort should be made 
to have the case report forms completed and signed as soon as possible following a subject’s 
study visit. 
IRC vendor is responsible for their own data handling as described in the independent review 
charter. 
11.2 
Data Management 
Clinical data management will be performed according to procedures described in the study 
Data Management Plan which will be subject to review and approval by Allogene. The Data 
Management Plan will include procedures for all aspects of the processing of the data from 
this study and, where clinical data management is outsourced, the responsibilities of the 
sponsor or designee. Adverse events and medications will be coded using MedDRA and the 
World Health Organization Drug Dictionary, respectively. The Data Management Plan will 
include specific details of which version of these dictionaries has been used. 
11.3 
Protocol Deviation 
A protocol deviation is any departure from the procedures and/or processes described in the 
study protocol as prepared by the sponsor, agreed to by the investigator and approved by the 
IRB/IEC.  
Protocol deviations should be reported to the sponsor or designee as they occur or are 
discovered and most of the time these will be documented in the study source records. In 
addition, protocol deviations should be reported to the IRB/IEC per IRB/IEC guidelines. The 
study monitor will document deviations discovered throughout the course of monitoring 
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visits, or medical review of the clinical database. These deviations, and any corrective actions 
taken, will be reviewed and discussed with the sponsor and the investigators as applicable. 
Study monitoring will be performed in accordance with ICH GCP, sponsor’s and/or the 
designee’s procedures, the protocol, and applicable local regulations. 
11.4 
Record Retention 
The investigator must make study data accessible to the Study Monitor or other authorized 
representatives of Allogene (or designee) and Regulatory Agency (eg, FDA) inspectors upon 
request. A file for each subject must be maintained that includes the signed informed consent 
form as well as all source documentation related to that subject. The investigator must ensure 
the reliability and availability of source documents from which the information on the case 
report form was derived. 
Subject identity information recorded will be maintained on the Subject Confidentiality Log 
for a duration in accordance with local requirements for an extended safety monitoring 
period. 
Investigators must maintain all study documentation for at least a period of 2 years following 
the approval of the drug, or until 2 years after the investigational drug program is 
discontinued; or in accordance with local requirements (if longer). Study documentation 
includes all Essential Documents as defined in ICH E6 Guidelines for Good Clinical 
Practice. Allogene or designee will notify the investigator when any records may be 
discarded. 
12. ETHICS 
12.1 
Institutional Review Board/Ethics Committee  
The IRB/EC must prospectively approve the study protocol, protocol amendments, informed 
consent documents, and other relevant documents, eg, recruitment advertisements, as 
applicable. All correspondence with the IRB/EC should be retained in the investigator file. 
Copies of IRB/EC approvals should be forwarded to the sponsor or its designee. 
The only circumstance in which an amendment may be initiated prior to IRB/EC approval is 
where the change is necessary to eliminate apparent immediate hazards to the subjects. In 
that event, the investigator must notify the IRB/EC and Allogene in writing immediately after 
the implementation. 
12.2 
Ethical Conduct of the Study 
The study will be conducted in accordance with the protocol, legal and regulatory 
requirements, and the general principles set forth in the International Ethical Guidelines for 
Biomedical Research Involving Human Subjects (Council for International Organizations of 
Medical Sciences 2002), ICH Guideline for Good Clinical Practice, the European Union 
Clinical Trial Regulation (EU-CTR) 536/2014, and the Declaration of Helsinki 
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12.3 
Subject Information and Consent 
Study Sites are required to comply with the data collection and processing requirements of 
the Study protocol, and the parties involved in the execution of this study (eg, the Sponsor, 
Contract Research Organization (“CRO”), Investigator, site staff and designees, employees, 
and agents) involved with the Study are obligated to comply with applicable local, state, 
federal, and regional laws, relating to the protection of personal data. CROs, laboratories, and 
contractors engaged by the Sponsor to support the execution of the clinical Study are subject 
to an assessment of implemented privacy and security controls and contractually obligated to 
implement appropriate safeguards to protect the personal data, including coded data, 
processed in the execution of the Study. 
The Investigator will obtain a signed Informed Consent Form from each Study Subject 
participating in the clinical Study. Thereafter, the Investigator and authorized Site personnel 
will obtain personal data of Study Subjects and review Study Subject information, including 
medical records, to complete and provide all necessary documents, information, and reports 
required by the Protocol.  To ensure that personal data of Study Subjects are kept 
confidential, the Subject’s name, contact information, and any other directly identifying 
information that allows the Subject to be directly identified will not be included in any 
records or samples that the Investigator or Study Site provides to the Sponsor or the 
Sponsor’s representatives. Instead, Study Subjects will be assigned a unique code (“Study 
ID”) that is not derived from information related to the Study Subject and may only be traced 
back to a particular individual by referencing a key, which will be securely maintained by the 
Study Site.  Investigator and Study Site will only identify the Subject with Sponsor and its 
representatives by such Study ID. Investigator and Study Site will store the Study ID in a 
secure area at all times. The study data entry and study management systems used by Study 
Sites, CROs, and the Sponsor will be secured, and password protected.  
At the end of the Study, Study Site shall ensure that all records containing personal data will 
continue to be kept in a secure location for as long a period as dictated by local Ethics 
Committees / IRB and Study Site regulations, and applicable law.  Results of the Study may 
be presented in reports, published in scientific journals, or presented at medical meetings; 
however, no directly identifying personal data of Study Subjects will be used. To ensure 
patient safety and in adherence with regulatory guidelines, Study Subject information may be 
reviewed by authorized Sponsor representatives, the IRB/IEC, and/or government regulatory 
authorities. 
Security incidents impacting personal data are managed pursuant to the Sponsor’s Privacy 
Event Management procedures, and all Sponsor personnel, third-party service providers, 
vendors and processors are required to report Privacy Events to the Sponsor Data Protection 
Officer or other appropriate management.  Sponsor shall determine the extent of the Event 
and potential impact to Study Subjects, mitigate risks as possible, and comply with 
applicable reporting obligations.  Study Site will employ reasonable efforts to adopt all of the 
technological and organizational measures required by applicable regulations to protect the 
data gathered to conduct the Study and protect against any accidental or illegitimate 
destruction or accidental loss or damage, alteration, disclosure, or unauthorized access to 
such data.   
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The informed consent documents and any subject recruitment materials must be in 
compliance with ICH GCP, local regulatory requirements, and legal requirements, including 
applicable privacy laws. The informed consent documents used during the informed consent 
process and any subject recruitment materials must be reviewed and approved by Allogene, 
approved by the IRB/EC before use, and available for inspection. 
The investigator must ensure that each study subject is fully informed about the nature and 
objectives of the study and possible risks associated with participation. The investigator, or a 
person designated by the investigator, will obtain written informed consent from each subject 
before any study-specific activity is performed. The investigator will retain the original of 
each subject’s signed consent document. 
12.4 
Reporting of Safety Issues and Serious Breaches of the Protocol or ICH GCP     
In the event of any prohibition or restriction imposed (ie, clinical hold) by an applicable 
regulatory authority in any area of the world, or if the investigator is aware of any new 
information that might influence the evaluation of the benefits and risks of the investigational 
product, Allogene should be informed immediately.  
In addition, the investigator will inform Allogene immediately of any urgent safety measures 
taken by the investigator to protect the study subjects against any immediate hazard, and of 
any serious breaches of this protocol or of ICH GCP that the investigator becomes aware of. 
13. DEFINITION OF END OF STUDY 
The overall trial begins when the first subject signs the informed consent form.  The overall 
trial ends when the last subject completes the last study-related visit or assessment, 
discontinues from the trial or is lost to follow-up (ie, the subject is unable to be contacted by 
the investigator). 
After participating in this study, subjects will be followed in a separate, noninterventional, 
long-term, safety-monitoring study (LTFU) for a combined total of 15 years. 
14. SPONSOR DISCONTINUATION CRITERIA 
Premature termination of this study may occur because of a regulatory authority decision, 
change in opinion of the IRB/EC, or investigational product safety problems, or at the 
discretion of Allogene. In addition, Allogene retains the right to discontinue development of 
ALLO-501A and/or ALLO-647 at any time. 
If the study is prematurely terminated, Allogene will promptly notify the investigator. After 
notification, the investigator must contact all participating subjects and the hospital pharmacy 
(if applicable) within 5 business days. As directed by Allogene, all study materials must be 
collected and all eCRFs completed to the greatest extent possible. 
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15. PUBLICATION OF STUDY RESULTS 
15.1 
Communication of Results by Allogene 
Allogene fulfills its commitment to publicly disclose clinical trial results through posting the 
results of studies on www.clinicaltrials.gov (ClinicalTrials.gov) and the European Clinical 
Trials Database (EudraCT), and other public registries in accordance with applicable local 
laws/regulations.  
In all cases, study results are reported by Allogene in an objective, accurate, balanced, and 
complete manner and are reported regardless of the outcome of the study or the country in 
which the study was conducted. 
www.clinicaltrials.gov 
Allogene posts clinical trial results as required by applicable law on www.clinicaltrials.gov 
for Allogene-sponsored interventional studies (conducted in subjects) that evaluate the safety 
and/or efficacy of an Allogene product. Results are submitted for posting within 1 year of the 
primary completion date.  
Primary completion date is defined as the date that the final subject was examined or 
received an intervention for the purposes of final collection of data for the primary outcome, 
whether the clinical study concluded according to the prespecified protocol or was 
terminated. 
EudraCT 
Allogene posts clinical trial results, as required by applicable laws, including European 
Union requirements, on EudraCT for all Allogene-sponsored interventional studies.  Results 
are submitted for posting within 1 year of the end of the clinical trial for studies in adult 
populations or within 6 months of the end for studies in pediatric populations. 
15.2 
Publications by Investigators 
Allogene supports the exercise of academic freedom and has no objection to publication by 
the principal investigator of the results of the study based on information collected or 
generated by the principal investigator, whether or not the results are favorable to the 
Allogene product, in a publication. Publication means any disclosure of the study results in a 
journal article, abstract, presentation, or any other type of public disclosure that reports any 
study results. To ensure against inadvertent disclosure of confidential information or 
unprotected inventions, the investigator will provide Allogene an opportunity to review any 
proposed publication before it is submitted or otherwise disclosed.  
The investigator will provide any publication to Allogene at least 60 days before it is 
submitted for publication or otherwise disclosed. If any patent action is required to protect 
intellectual property rights or other proprietary rights, the investigator agrees to delay the 
disclosure for a period not to exceed an additional 60 days. 
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The investigator will, on request, remove any confidential information belonging to Allogene 
before disclosure. For the purpose of publication, the study results are not considered the 
confidential information of Allogene.  
If the study is part of a multicenter study, the investigator agrees that the first publication is 
to be a joint publication covering all investigator sites, and that any subsequent publications 
by the principal investigator will reference that primary publication. However, if a joint 
manuscript has not been submitted for publication within 18 months of completion or 
termination of the study at all participating sites, the principal investigator is free to publish 
separately, subject to the other requirements of this section. 
For all publications relating to the study, the institution and principal investigator will 
comply with recognized ethical standards concerning publications and authorship, including 
Section II - “Ethical Considerations in the Conduct and Reporting of Research” of the 
Uniform Requirements for Manuscripts Submitted to Biomedical Journals, 
http://www.icmje.org/index.html#authorship, established by the International Committee of 
Medical Journal Editors. 
Publication of study results is also provided for in the Clinical Trial Agreement (CTA) 
between Allogene and the institution. In this section entitled Publications by investigators, 
the defined terms shall have the meanings given to them in the CTA. 
If there is any conflict between the CTA and any attachments to it, the terms of the CTA 
control. If there is any conflict between this protocol and the CTA, this protocol will control 
as to any issue regarding treatment of study subjects, and the CTA will control as to all other 
issues. 
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Poirot L, Philip B, Schiffer-Mannioui C, et al. Multiplex genome-edited T-cell 
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Precision Biosciences website. 04 December 2020. Overcoming Cancer Interim Results for 
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https://investor.precisionbiosciences.com/news-releases/news-release-details/precision-
biosciences-reports-positive-interim-results-pbcar0191 
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cytokine release syndrome after chimeric antigen receptor T-cell therapy.  Ther Clin Risk 
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APPENDIX 1 
ABBREVIATIONS  
Abbreviation 
Definition 
A 
ALLO-647 
ADA 
anti-drug antibody 
ADCC 
antibody-dependent cell-mediated cytotoxicity 
AE 
adverse event  
ALC 
absolute lymphocyte count 
Alk Phos 
alkaline phosphatase 
ALT 
alanine aminotransferase 
ANC 
absolute neutrophil count 
ASBMT 
American Society for Bone and Marrow Transplantation 
AST 
aspartate aminotransferase  
ASTCT 
American Society for Transplantation and Cellular Therapy 
B-NHL 
B-cell non-Hodgkin lymphoma 
BM 
bone marrow 
BP 
blood pressure 
BOR 
best overall response 
BUN 
blood urea nitrogen 
C 
cyclophosphamide 
CAR 
chimeric antigen receptor 
CAR T 
chimeric antigen receptor T cells 
CBC 
complete blood cell count 
CD 
cluster of differentiation  
CDC 
complement-dependent cytotoxicity 
CMV 
cytomegalovirus 
CNS 
central nervous system 
CR 
complete response 
CRP 
C-reactive protein 
CRS 
cytokine release syndrome  
CTA 
clinical trial agreement 
CTCAE 
Common Terminology Criteria for Adverse Events 
C or Cy 
cyclophosphamide 
DILI 
drug-induced liver injury 
DLBCL 
diffuse large B-cell lymphoma 
DLT 
dose-limiting toxicity 
DMC 
data monitoring committee 
DOR 
duration of response 
DSA 
donor specific antibody 
DSMB 
data and safety monitoring board 
EBV 
Epstein-Barr virus 
EC 
Ethics Committee 
ECG 
electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group  
EDP 
exposure during pregnancy 
ELISA 
enzyme-linked immunosorbent assay 
EORTC QLQ-C30 
European Organisation for Research and Treatment of Cancer Quality of Life 
Questionnaire C-30 
EOS 
end of study 
EQ-5D 
EuroQol standardized instrument 
EudraCT 
European Union Drug Regulating Authorities Clinical Trials 
F or Flu 
fludarabine 
Fc 
fragment, crystallizable 
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Abbreviation 
Definition 
GCP 
Good Clinical Practice 
GLP 
Good Laboratory Practice 
GVHD 
graft-vs-host disease 
HBC 
hepatitis B core 
HCV 
hepatitis C virus 
HLA 
human leukocyte antigen 
HSCT 
hematopoietic stem cell transplant 
ICANS 
immune effector cell-associated neurotoxicity syndrome 
ICE 
Immune Effector Cell-Associated Encephalopathy 
IFN 
interferon gamma 
Ig 
immunoglobulin 
IMP 
investigational medicinal products 
IND 
Investigational New Drug 
INR 
International normalized ratio 
IP 
investigational product 
IRB 
Institutional Review Board 
IRC 
Independent Radiology Committee 
IV 
intravenous 
KM 
Kaplan-Meier 
LDH 
lactate dehydrogenase 
LVEF 
left ventricular ejection fraction 
LVV 
lentiviral vector 
LTFU 
long-term follow up 
mAb 
monoclonal antibody 
MedDRA 
Medical Dictionary for Regulatory Activities 
MHC 
major histocompatibility 
mITT 
modified intent-to-treat 
mRNA 
messenger ribonucleic acid 
MRD 
minimal residual disease  
MRI 
magnetic resonance imaging 
MUGA 
multi-gated acquisition scan 
NAb 
neutralizing antibody 
NCI CTCAE 
National Cancer Institute Common Terminology Criteria for Adverse Events 
NHL 
non-Hodgkin lymphoma 
NK 
natural killer 
ORR 
overall response rate 
OS 
overall survival  
PBMC 
peripheral blood mononuclear cell 
PCR 
polymerase chain reaction 
PD 
progressive disease 
PET 
positron emission tomography 
PFS 
progression-free survival 
PK 
pharmacokinetics 
PR 
partial response 
PRO 
patient-reported outcome 
PT 
prothrombin time 
PTT 
partial thromboplastin time 
QLQ 
Quality of Life Questionnaire 
QoL 
quality of life 
qPCR 
quantitative polymerase chain reaction 
RCL 
replication competent lentivirus 
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Abbreviation 
Definition 
R/R 
relapsed or refractory  
RP2D 
recommended Phase 2 dose 
SAE 
serious adverse event 
SAP 
Statistical Analysis Plan 
scFv 
single-chain variable fragment 
SD 
stable disease 
TALEN 
transcription activator-like effector nucleases  
TBili 
total bilirubin  
TCR 
T cell receptor 
TRAC 
T cell receptor alpha constant  
TSH 
thyroid stimulating hormone 
TTR 
time to response 
UCART19 
universal engineered chimeric antigen receptor T cells targeting CD19 
ULN 
upper limit of normal 
VAS 
visual analog scale 
VCN 
vector copy number 
WBC 
white blood cell 
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APPENDIX 3 
ACUTE GVHD GRADING 
GvHD Target Organ Staging (Harris et al, 2016) 
Stage 
Skin  
(Active Erythema 
Only) 
Liver 
(Bilirubin) 
Upper GI 
Lower GI (stool output/day) 
0 
No active  
(erythematous) 
GVHD rash 
<2 mg/dL 
No or intermittent 
nausea, vomiting, or 
anorexia 
Adult: <500 mL/day or 
<3 episodes/day  
Child: <10 mL/kg/day or 
<4 episodes/day 
1 
Maculopapular rash 
<25% BSA 
2-3 mg/dL 
Persistent nausea, 
vomiting or 
anorexia 
Adult: 500-999 mL/day or 3-4 
episodes/day 
Child: 10-19.9 mL/kg/day or 4-
6 episodes/day 
2 
Maculopapular rash 
25-50% BSA 
3.1-6 mg/dL 
 
Adult: 1000-1500 mL/day or 5-
7 episodes/day  
Child: 20-30 mL/kg/day or 7-
10 episodes/day 
3 
Maculopapular rash 
>50% BSA 
6.1-15 mg/dL 
 
Adult: >1500 mL/day or 
>7 episodes/day  
Child: >30 mL/kg/day or 
>10 episodes/day 
4 
Generalized 
erythroderma 
(>50% BSA) plus 
bullous formation 
and desquamation 
>5% BSA 
>15 mg/dL 
 
Severe abdominal pain with or 
without ileus or grossly bloody 
stool (regardless of stool 
volume). 
Overall clinical grade (based on most severe target organ involvement):  
- Grade I: Stage 1-2 skin without liver, upper GI, or lower GI involvement. 
- Grade II: Stage 3 rash and/or stage 1 liver and/or stage 1 upper GI and/or stage 1 lower GI. 
- Grade III: Stage 2-3 liver and/or stage 2-3 lower GI, with stage 0-3 skin and/or stage 0-1 
upper GI. Grade IV: Stage 4 skin, liver, or lower GI involvement, with stage 0-1 upper GI. 
 
 
 
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APPENDIX 5 
CYTOKINE RELEASE SYNDROME MANAGEMENT  
CRS Grade 
Tocilizumab * 
Corticosteroids  
Grade 1  
N/A  
N/A  
Grade 2  
Administer tocilizumab 8 mg/kg 
intravenously over 1 hour (not to exceed 
800 mg).  
Repeat tocilizumab every 8 hours as 
needed if not responsive to intravenous 
fluids or increasing supplemental oxygen.  
Limit to a maximum of 3 doses in a 24-
hour period; maximum total of 4 doses.  
For CRS Grade 2 and above, a second line 
agent (eg, siltuximab or anakinra) may be 
considered for use if not responsive to 
initial dose of tocilizumab. 
Administer methylprednisolone 1 mg/kg 
intravenously twice daily or equivalent 
dexamethasone (eg, 10 mg intravenously 
every 6 hours).  
Continue corticosteroids use until the 
event is Grade 1 or less, then taper over 3 
days. 
Grade 3 
Per Grade 2  
Per Grade 2 
Grade 4 
Per Grade 2 
If no CRS improvement after 4 doses of 
tocilizumab, consider alternate anti-
cytokine therapy eg, siltuximab 
Administer methylprednisolone 1000 mg 
intravenously per day for 3 days; if 
improves, then manage as above. 
Subjects who experience Grade 2 or higher CRS (eg, hypotension, not responsive to fluids, 
or hypoxia requiring supplemental oxygenation) should be monitored with continuous 
cardiac telemetry and pulse oximetry. For subjects experiencing Grade ≥3 CRS, an 
echocardiogram should be performed to assess cardiac function and subjects should be 
promptly considered for intensive care supportive therapy. 
*In the event that tocilizumab has a pandemic-related shortage, a second line agent (eg, 
siltuximab or anakinra) may be considered for use if not responsive to initial dose of 
tocilizumab.  If tocilizumab is unavailable follow institutional guidelines and use appropriate 
alternatives. 
The treatment for CRS is not supplied by Allogene. 
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APPENDIX 6 
MANAGEMENT OF INFUSION RELATED REACTIONS 
INCLUDING ALLERGIC REACTIONS OR ANAPHYLAXIS WITH ALLO-647 
In the event of infusion related reactions, investigators should institute treatment measures 
according to best medical and nursing practice. 
The following treatment guidelines should be employed: 
If chills and fever (>100.4F/38.0C) occur, the infusion should be interrupted. Subjects may 
be treated symptomatically and the infusion should be restarted at 50% of the original rate.  
Hypersensitivity reactions: 
1. NCICTCAE Grade 1 allergic reaction 
• Monitor for worsening condition. If the reaction worsens, stop the infusion. Institute 
premedication for subsequent infusions as per Section 5.6.2.1.  
2. NCICTCAE Grade 2 allergic reaction 
• Stop ALLO-647 infusion. 
• Administer bronchodilators, oxygen, acetaminophen, etc. as medically indicated. 
• Resume infusion at 50% of previous rate once reaction has decreased to Grade 1 in 
severity. Monitor closely for any worsening. If the reaction recurs, stop infusion. 
Institute premedication for subsequent infusions as per Section 5.6.2.1. 
3. NCICTCAE Grade 3 or Grade 4 allergic reaction or anaphylaxis 
• A Grade 3 anaphylaxis (hypersensitivity reaction) consists of symptomatic 
bronchospasm requiring parenteral medications with or without urticaria, 
allergyrelated oedema/angioedema, or hypotension. 
• A Grade 4 anaphylaxis (hypersensitivity reaction) is a life-threatening event requiring 
urgent intervention. 
4. Treatment of Grade 3 or Grade 4 allergic reaction or anaphylaxis 
• Stop the ALLO-647 infusion immediately and disconnect infusion tubing from the 
subject. 
• Administer epinephrine, bronchodilators, antihistamines, glucocorticoids, intravenous 
fluids, vasopressor agents, oxygen, etc. as medically indicated. 
• Telephone sponsor or designated representative to report an SAE as per Section 8. 
• For an NCICTCAE Grade 4 hypersensitivity reaction, study treatment will be 
discontinued. 
5. Resume treatment following Grade 1 or Grade 2 allergic reactions 
• Once the ALLO-647 infusion rate has been decreased due to an allergic reaction, it 
will remain decreased for all subsequent infusions. 
• If the subject has a second reaction at the lower infusion rate, the infusion should be 
stopped and the subject should receive no further ALLO-647. 
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• If the subject experiences a Grade 4 allergic reaction or anaphylaxis at any time, the 
subject should receive no further ALLO-647. Discuss with sponsor medical monitor 
if suspected Grade 3 infusion reaction to ALLO-647 occurs. 
• If there are questions concerning whether an observed infusion-related reaction is 
consistent with an allergic reaction or anaphylaxis, the medical monitor should be 
contacted immediately to assist with grading the reaction. 
PK, pharmacodynamic, and ADA sampling should continue as long as the sampling does not 
interfere with the medical treatment of the subject. 
In cases of suspected cytokine release syndrome, a serum sample should be provided for 
cytokine release assay analysis so as long as the sampling does not interfere with the medical 
treatment of the subject. 
 
 
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APPENDIX 7 
BONE MARROW RESERVE IN ADULTS 
SITE 
MARROW 
wt. (g) 
FRACTION 
RED 
MARROW 
AGE 40 
RED 
MARROW 
wt. (g) 
AGE 40 
% TOTAL 
RED MARROW 
CRANIUM 
Head: 
 
 
136.6 
 
 
AND 
 
Cranium 
165.8 
0.75 
124.3 
13.1 
13.1 
MANDIBLE 
 
Mandible 
16.4 
0.75 
12.3 
 
 
HUMERI, 
SCAPULAE, 
CLAVICLES 
Upper Limb Girdle: 
 
 
86.7 
 
 
 
2 Humerus,  
 
head & neck 
26.5 
0.75 
20.0 
8.3 
8.3 
 
2 Scapulae  
67.4 
0.75 
50.5 
 
 
 
2 Clavicles 
21.6 
0.75 
16.2 
 
 
STERNUM 
AND RIBS 
Sternum 
39.0 
0.6 
23.4 
2.3 
 
Ribs:  
 
 
82.6 
 
 
 
1 pair 
10.2 
All 0.4 
4.1 
 
 
 
2  
12.6 
 
5.0 
 
 
 
3 
16.0 
 
6.4 
 
 
 
4 
18.6 
 
7.4 
 
 
 
5 
23.8 
 
9.5 
7.9 
10.2 
 
6 
23.6 
 
9.4 
 
 
 
7 
25.0 
 
10.0 
 
 
 
8 
24.0 
 
9.6 
 
 
 
9 
21.2 
 
8.5 
 
 
 
10 
16.0 
 
6.4 
 
 
 
11 
11.2 
 
4.5 
 
 
 
12 
4.6 
 
1.8 
 
 
PELVIC 
BONES 
Sacrum  
194.0 
0.75 
145.6 
13.9 
 
2 os coxae 
310.6 
0.75 
233.0 
22.3 
36.2 
FEMUR 
2 Femoral head  
and neck 
53.0 
0.75 
40.0 
 
3.8 
 
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Appendix 6 
Bone Marrow Reserve in Adults (continued) 
SITE 
MARROW 
wt. (g) 
FRACTION RED 
MARROW 
AGE 40 
RED 
MARROW 
wt. (g) 
AGE 40 
% TOTAL 
RED MARROW 
VERTEBRAE 
Vertebrae 
(Cervical): 
 
 
35.8 
 
 
1 
6.6 
All 0.75 
5.0 
 
 
2 
8.4 
 
6.3 
 
 
3 
5.4 
 
4.1 
3.4 
 
4 
5.7 
 
4.3 
 
 
5 
5.8 
 
4.4 
 
 
6 
7.0 
 
5.3 
 
 
7 
8.5 
 
6.4 
 
 
Vertebrae 
(Thoracic): 
 
 
147.9 
 
 
1 pair 
10.8 
All 0.75 
8.1 
 
 
2 
11.7 
 
8.8 
 
 
3 
11.4 
 
8.5 
 
 
4 
12.2 
 
9.1 
 
 
5 
13.4 
 
10.1 
14.1 
28.4 
6 
15.3 
 
11.5 
 
 
7 
16.1 
 
12.1 
 
 
8 
18.5 
 
13.9 
 
 
9 
19.7 
 
14.8 
 
 
10 
21.2 
 
15.9 
 
 
11 
21.7 
 
16.3 
 
 
12 
25.0 
 
18.8 
 
 
Vertebrae 
(Lumbar): 
 
 
114.1 
 
 
1 pair 
27.8 
All 0.75 
20.8 
 
 
2 
29.1 
 
21.8 
10.9 
 
3 
31.8 
 
23.8 
 
 
4 
32.1 
 
24.1 
 
 
5 
31.4 
 
23.6 
 
 
TOTAL 
 
1497.7 
 
1045.7 
100.0 
100.0 
Adapted from Ellis RE, 1961 
 
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APPENDIX 8 
ASTCT IMMUNE EFFECTOR CELL-ASSOCIATED 
ENCEPHALOPATHY (ICE) SCORE 
ICE Encephalopathy Assessment Tool for Grading of ICANS 
Orientation 
Orientation to year, month, city, hospital 
4 points 
Naming 
Ability to name 3 objects (eg, point to clock, pen, button) 
3 points 
Following 
Commands 
Ability to follow simple commands (eg, “Show me 2 
fingers” or “Close your eyes and stick out your tongue”) 
1 point 
Writing 
Ability to write a standard sentence (eg, “Our national bird 
is the bald eagle”) 
1 point 
Attention 
Ability to count backwards from 100 by 10 
1 point 
Abbreviations: ASBMT = American Society for Bone and Marrow Transplant; ICANS = immune effector cell-associated 
neurotoxicity syndrome; ICE = Immune Effector Cell-Associated Encephalopathy 
Scoring: 10, no impairment; 
7-9, grade 1 ICANS; 
3-6, grade 2 ICANS; 
0-2, grade 3 ICANS; 
0 due to patient unarousable and unable to perform ICE assessment, grade 4 ICANS 
 
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APPENDIX 9 
ASTCT ICANS CONSENSUS GRADING FOR ADULTS 
Neurotoxicity 
Domain 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
ICE scorea 
7-9 
3-6 
0-2 
0 (patient is 
unarousable and unable 
to perform ICE) 
Depressed level 
of 
consciousnessb 
Awakens 
spontaneously 
Awakens to 
voice 
Awakens only to 
tactile stimulus 
Patient is unarousable 
or requires vigorous or 
repetitive tactile stimuli 
to arouse. Stupor or 
coma 
Seizure 
N/A 
N/A 
Any clinical seizure 
focal or generalized 
that resolves rapidly 
or nonconvulsive 
seizures on EEG that 
resolve with 
intervention 
Life-threatening 
prolonged seizure (>5 
min); or Repetitive 
clinical or electrical 
seizures without return 
to baseline in between 
Motor findingsc 
N/A 
N/A 
N/A 
Deep focal motor 
weakness such as 
hemiparesis or 
paraparesis 
Elevated ICP/ 
cerebral edema 
N/A 
N/A 
Focal/local edema 
on neuroimagingd 
Diffuse cerebral edema 
on neuroimaging; 
decerebrate or 
decorticate posturing; 
or cranial nerve VI 
palsy; or papilledema; 
or Cushing's triad 
Abbreviations: ASBMT = American Society for Bone and Marrow Transplant; CTCAE = Common Terminology Criteria 
for Adverse Events; ICANS = immune effector cell-associated neurotoxicity syndrome; ICE = Immune Effector Cell-
Associated Encephalopathy; ICP = intracranial pressure; N/A = not applicable 
ICANS grade is determined by the most severe event (ICE score, level of consciousness, seizure, motor findings, raised 
ICP/cerebral edema) not attributable to any other cause; for example, a patient with an ICE score of 3 who has a 
generalized seizure is classified as grade 3 ICANS. 
a A patient with an ICE score of 0 may be classified as grade 3 ICANS if awake with global aphasia, but a patient with an 
ICE score of 0 may be classified as grade 4 ICANS if unarousable. 
b Depressed level of consciousness should be attributable to no other cause (eg, no sedating medication). 
c Tremors and myoclonus associated with immune effector cell therapies may be graded according to CTCAE v5.0, but 
they do not influence ICANS grading. 
d Intracranial hemorrhage with or without associated edema is not considered a neurotoxicity feature and is excluded from 
ICANS grading. It may be graded according to CTCAE v5.0 
 
 
 
 
 
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APPENDIX 10 
NEUROLOGIC TOXICITY MANAGEMENT GUIDANCE 
Grading Assessment  
Concurrent CRS  
No concurrent CRS  
Grade 1 
Supportive care 
Supportive care 
Grade 2  
Administer tocilizumab for 
management of Grade 2 CRS*.  
In addition, administer 
dexamethasone 10 mg 
intravenously every 6 hours if not 
already taking other corticosteroids. 
Continue dexamethasone use until 
the event is Grade 1 or less, then 
taper over 3 days.  
Consider non-sedating, anti-seizure 
medicines (eg, levetiracetam) for 
seizure prophylaxis 
Administer dexamethasone 10 mg 
intravenously every 6 hours.  
Continue dexamethasone use until 
the event is Grade 1 or less, then 
taper over 3 days.  
Consider non-sedating, anti-seizure 
medicines (eg, levetiracetam) for 
seizure prophylaxis 
Grade 3  
Administer tocilizumab for 
management of Grade 2 CRS*.  
In addition, administer 
dexamethasone 10 mg 
intravenously with the first dose of 
tocilizumab and repeat dose every 
6 hours. Continue dexamethasone 
use until the event is Grade 1 or 
less, then taper over 3 days.  
Consider non-sedating, anti-seizure 
medicines (eg, levetiracetam) for 
seizure prophylaxis 
Administer dexamethasone 10 mg 
intravenously every 6 hours.  
Continue dexamethasone use until 
the event is Grade 1 or less, then 
taper over 3 days.  
Consider non-sedating, anti-seizure 
medicines (eg, levetiracetam) for 
seizure prophylaxis 
Grade 4  
Administer tocilizumab for 
management of Grade 2 CRS*.  
Administer methylprednisolone 
1000 mg intravenously per day 
with first dose of tocilizumab and 
continue methylprednisolone 
1000 mg intravenously per day for 
2 more days; if improves, then 
manage as above.  
If no CRS improvement after 4 
doses of tocilizumab, consider 
alternate anti-cytokine therapies 
eg, siltuximab 
Consider non-sedating, anti-seizure 
medicines (eg, levetiracetam) for 
seizure prophylaxis 
Administer methylprednisolone 
1000 mg intravenously per day for 
3 days; if improves, then manage as 
above.  
Consider non-sedating, anti-seizure 
medicines (eg, levetiracetam) for 
seizure prophylaxis 
Note: Consider non-sedating, anti-seizure medicines (eg, levetiracetam) for seizure prophylaxis. 
*In the event of a pandemic-related tocilizumab shortage a second line agent (eg, siltuximab) may be 
considered for use if not responsive to initial dose of tocilizumab. 
 
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APPENDIX 12 
SCHEDULE OF ACTIVITIES  
The Schedule of Activities provides an overview of the protocol visits and procedures. Refer to the Assessments section (Section 7) of 
the protocol for detailed information on each assessment required for compliance with the protocol. 
The investigator may schedule visits (unplanned visits) in addition to those listed in the Schedule of Activities to conduct evaluations 
or assessments required to protect the well-being of the subject.  
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7  Vital Signs: Includes temperature (oral, tympanic, temporal or axillary), blood pressure (BP), pulse rate and oxygen saturation level. Oxygen saturation will be 
evaluated by pulse oximetry. On 
, to be performed 
. 
8  ICE Assessment/ ICANS.  Conduct immune effector cell-associated encephalopathy (ICE) score at screening.  Conduct ICE score and immune effector cell-
associated neurotoxicity syndrome (ICANS) grading as clinically indicated, starting on 
 ICE and ICANS grading scales are provided in 
Appendix 8.  
9 12 Lead electrocardiogram (ECG): At each time point, 12 lead ECG will be performed to determine cardiac safety and QTcF interval. On 
, ECG will 
be performed prior to investigational product administration. If the QTcF is prolonged (>500 msec), the ECG should be re-evaluated by a qualified person at 
the institution for confirmation. 
10 Donor-specific anti-human leukocyte antigen (HLA) antibodies (DSA): Screening: Samples will be collected and sent to a central laboratory for 
processing and analysis after the subject signs the pre-screening or screening informed consent form. Donor-specific anti-HLA antibodies must be repeated 
prior to 
 if subject receives blood transfusion (ie, red blood cells, platelets, plasma) after an initial negative result to confirm eligibility. 
11 CBC Hematology: complete blood count (CBC) with differential (should include % and absolute number of neutrophils, lymphocytes, monocytes, 
eosinophils, basophils, and reticulocyte count), hemoglobin, hematocrit, platelet counts. On
, hematology will be performed 
 
. On 
, samples will be collected 
 infusion. 
12 Blood Chemistry (fasting not required): should include: alanine aminotransferase (ALT), albumin, alkaline phosphatase, aspartate aminotransferase (AST), 
bicarbonate, total bilirubin, blood urea nitrogen (BUN), chloride, serum calcium, creatinine, creatinine clearance, glucose, lactate dehydrogenase, 
magnesium, sodium, phosphorus or phosphate, total protein, potassium, uric acid, serum ferritin, C-reactive protein (CRP). On 
, chemistry will be 
performed prior to start of lymphodepletion treatment. On 
 samples will be collected prior to ALLO-501A infusion. 
13 Coagulation: fibrinogen and D-dimer, partial thromboplastin time (PTT) and International Normalized Ratio (INR) or prothrombin time. 
14 Reflex auto-antibodies will be evaluated in case of suspected ALLO-647 treatment emergent autoimmunity AE. Depending on the type of AE, the tests 
should include (but not limited to) serum antiphospholipid antibodies (APA), platelet-bound APA, anti-Factor VIII antibodies, anti-Thyroid Peroxidase (anti-
TPO), anti-Thyroglobulin (anti-TG) and anti-thyroid stimulating hormone (anti-TSH receptor), Coombs test, antinuclear antibodies (ANA), perinuclear anti-
neutrophil cytoplasmic antibodies (P-ANCA), anti-neutrophil cytoplasmic antibodies (cANCA), and/or anti-Sjogren’s syndrome type B (anti-SSB). 
15 Urinalysis: Urine dipstick for protein, glucose, and blood: If positive collect 24 hr and/or microscopic cell count (Reflex Testing). 
16 Pregnancy test and contraception check: Serum or urine pregnancy test for females of childbearing potential. Follicle stimulating hormone test may be 
performed for post-menopausal women. Contraception use will be checked to confirm that contraception is used consistently and correctly. 
17 Replication competent lentivirus (RCL): Whole blood samples will be collected to monitor for the presence of RCL-specific DNA sequences by a validated 
PCR-based assay.  Samples may be analyzed for RCL only 
; if negative, then remaining samples 
 may be collected and 
archived.  Assess for RCL upon diagnosis of a new (secondary) malignancy.   
18 Quantitative serum immunoglobulins (local analysis): Humoral immunity will be monitored by the measurement of serum IgG, IgA, and IgM levels. On 
, samples will be collected prior to investigational product administration.  
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19 Lymphodepletion:  
• 
Fludarabine (FC and FCA arms): 30 mg/m2/day fludarabine will be administered IV over approximately 15 to 30 minutes for 3 days, from Day -5 to 
Day -3.  The fludarabine dose should be adjusted based on renal function; for subjects with creatinine clearance <80 mL/min, the fludarabine dose 
should be 20 mg/m2 on each of the 3 dosing days or as per institutional guidelines. 
• 
Cyclophosphamide (FC and FCA arms): 300 mg/m2/day cyclophosphamide will be administered by IV over approximately 1 hr for 3 days, from 
Day -5 to Day -3.  
• 
ALLO-647 (FCA arm only): Administer 30 mg/d IV over approximately 4 hrs each day.  For FCA-90, 30 mg/day x 3 days, from Day -5 to Day -3.  
20 Lymphoma assessments by positron emission tomography (PET)/computerized tomography (CT): tumor assessments will include all known or 
suspected disease sites. Disease-specific imaging as clinically appropriate will be performed as described in the study imaging manual. All scans will also be 
sent to a central radiology vendor, as specified in the study imaging manual. If a PET/CT was performed within
 prior to Screening, then the results 
may be used for Screening disease assessment and a Screening PET/CT does not need to be done, providing there was no intervening therapy between the 
time of the PET/CT and Screening.  Radiographic disease assessment will not be required after documented disease progression per Lugano criteria or 
initiation of subsequent anti-cancer therapy. 
21 Brain MRI:  Subjects with a history of CNS disease: screening brain MRI must be stable as compared to previous brain MRI scan. 
22 Bone Marrow Biopsy and Aspirate: Bone marrow biopsy and aspirate will be completed 
, and at the time complete response (CR) is suspected 
only if bone marrow infiltration is positive or unknown at screening. Samples (screening; others as indicated) will be banked, and may be analyzed for 
insertion site analysis, molecular analysis, and other similar analyses. Proceduralist should  aim to achieve a 2cm core to best assess cellularity. 
23 Lymphoma biopsy: An archival formalin-fixed paraffin-embedded (FFPE) cancer tissue block from initial diagnosis, or previously obtained cancer tissue 
biopsy obtained prior to screening, may be submitted in place of a fresh sample, if obtained within 
 and if the subject received no 
intervening systemic anti-cancer treatment during this period. Cancer tissue from cytological sampling (eg, fine needle aspirates, including FFPE cell 
pelletthe  material) is not adequate and should not be submitted. The FFPE tissue blocks must be of sufficient size to obtain approximately 22-26 unstained 
slides which should be submitted to the central laboratory.  For subjects who undergo a fresh biopsy 
, or an on-treatment biopsy, a total of 3 core 
biopsies are to be obtained when possible for translational analyses. 
24 MRD assessment: A plasma sample will be collected for MRD analysis using ClonoSeq or equivalent testing. 
25 EQ-5D-5L (PRO) and QLQ-C30 (PRO): Completion of these instruments is not required after documented disease progression per Lugano criteria or 
initiation of subsequent anti-cancer therapy. 
26 ALLO-501A in blood (flow cytometry): A blood sample will be collected to quantify ALLO-501A by a validated flow cytometry-based cellular-kinetics 
assay on 
, and at the indicated time points by central laboratory. Phenotypic subsets of CAR + T cells such as memory, 
activated and exhausted populations may also be characterized. 
27 ALLO-501A in blood (transgene levels): A blood sample will be collected into a tube optimized for DNA isolation on 
, at the end of infusion on 
 
 (ie, within 30 min after infusion), and at the indicated time points to quantify ALLO-501A transgene levels by a validated qPCR-based transgene assay, 
performed by central laboratory. 
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28 ALLO-501A detection in lymph node, BM, and CSF: A sample of the indicated tissues will be evaluated to investigate the quantity of ALLO-501A in 
tissue compartments that may harbor tumor cells as clinically indicated. ALLO-501A may be measured by flow cytometry and/or qPCR-based assays by 
central laboratory.  If subject experiences prolonged (>42 days) cytopenia a bone marrow aspirate will be collected for TCR clonality assessment, central 
CAR flow cytometry analysis, VCN and potential RNASeq. CSF will be collected, as clinically indicated, at any time if Grade 3 and above ALLO-501A 
related neurological AEs and/or suspected encephalitis are observed. In addition to the ALLO-501A detection, infectious workup (including HHV) may also 
be performed with the CSF sample collected.  
29 ALLO-647 pharmacokinetics (PK) assessment (FCA arm only):  Blood samples will be collected at each time point for PK analysis of ALLO-647.  
ALLO-647 serum concentration will be measured by immunoassay during and following ALLO-647 infusions at the following time-points:  FCA-90: on 
 pre-dose, and end of infusion (within 15 minutes), 
 pre-dose, and end of infusion (within 15 minutes), 
 pre-dose, and end of infusion 
(within 15 minutes). 
 collect sample pre-ALLO-501A infusion, and at subsequent days as shown in the schedule. Testing will be performed at a 
central laboratory.   
30 Fludarabine and cyclophosphamide pharmacokinetics (PK) assessment (FC and FCA arms): Blood samples will be collected at each time point for PK 
analysis of fludarabine and cyclophosphamide.  Fludarabine and cyclophosphamide concentration will be measured by immunoassay during and following 
fludarabine and cyclophosphamide infusions at the following time-points:  on 
 pre-dose, end of  fludarabine infusion (within 15 minutes), end of  
cyclophosphamide infusion (within 15 minutes), 
 pre-dose, end of  fludarabine infusion (within 15 minutes), end of cyclophosphamide infusion 
(within 15 minutes), 
 pre-dose, and end of  fludarabine infusion (within 15 minutes), end of  cyclophosphamide infusion (within 15 minutes).  
 
collect sample pre-ALLO-501A infusion, and at subsequent days as shown in the schedule. Testing will be performed at a central laboratory.   
31 Cytokines and Soluble Proteins: Analysis will be completed at a central lab. Serum cytokines assessed for cytokine release syndrome (CRS) safety 
management will be managed locally. On
, the cytokine assessment (blood) will be performed prior to start of lymphodepletion treatment. On 
, samples will be collected prior to ALLO-501A infusion. 
32 Anti-ALLO-501A Antibodies (anti-scFv and anti-TALEN antibodies): A blood sample will be collected into a tube optimized for serum isolation to 
monitor for the development of ALLO-501A and TALEN-specific antibodies. Testing will be performed at a central laboratory. 
33 Anti-ALLO-647 Anti-Drug-Antibodies (FCA arm only): circulating levels of human anti-ALLO-647 antibodies will be assessed in serum by 
immunoassays up to
 or up to 2 consecutive negative tests post-dosing completion whichever is the latest. Neutralizing antibody testing will be 
performed only in case of positive anti-drug antibody (ADA). Testing will be performed at a central laboratory.  
34 Donor-specific anti-human leukocyte antigen (HLA) antibodies (DSA): (On study):  Binding of C1q to HLA Class I and II DSA will be tested in case of 
positive DSA results following 
. 
35 TBNK Assay: A blood sample will be collected for the enumeration of T, B, and natural killer (NK) cells by a flow cytometry-based assay to monitor the 
depth and duration of lymphodepletion. Samples will be collected before administration of ALLO-647 (
) or ALLO-
501A (
). Testing will be performed at a central laboratory. 
36 Gene expression (RNA) profile: Gene expression in whole blood associated with CART cell phenotype, activation state, and anti-tumor activity will be 
measured by RNA sequencing in blood, and bone marrow if bone marrow is collected to monitor response. Testing will be performed at a central laboratory.  
37 TCR sequencing: Whole blood samples will be collected into a tube optimized for isolation of DNA at the indicated time point to assess the clonality of 
ALLO-501A, the subject T cell repertoire by TCR sequencing analysis by a central laboratory. Testing will be performed at a central laboratory.  
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38 Genomic safety biospecimen: Unless prohibited by local regulations or ethics committee decision, a blood sample will be collected during 
, and 
, for assays related to treatment response in the disease under study, e.g. insertion site analysis, malignancy panels, 
microbial cell–free DNA (mcfDNA) for pathogens that cause infections, etc.  
39 Banked serum and plasma samples: Serum and plasma samples will be collected at the indicated timepoints and banked for future studies including 
endemic infectious diseases (e.g. HHV-6/7).  
40 PBMCs: Peripheral blood mononuclear cells (PBMCs) will be collected at the indicated timepoints and cryopreserved for future cytogenetics, cellular, 
molecular or proteomic studies.  
41 Focal CNA or risk score: A plasma sample will be collected for focal copy number alteration (CNA) or risk score (Cherng et al, 2022). 
 
 
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4  Blood Chemistry (fasting not required): should include: alanine aminotransferase (ALT), albumin, alkaline phosphatase, aspartate aminotransferase (AST), 
bicarbonate, total bilirubin, blood urea nitrogen (BUN), chloride, serum calcium, creatinine, creatinine clearance, glucose, lactate dehydrogenase, 
magnesium, sodium, phosphorus or phosphate, total protein, potassium, uric acid, serum ferritin, C- reactive protein (CRP). Not required after documented 
disease progression per Lugano criteria or initiation of subsequent anti-cancer therapy. 
5  TSH (FCA arm only) 
6  Urinalysis (FCA arm only): Urine dipstick for protein, glucose, and blood: If positive collect 24 hr and/or microscopic cell count (Reflex Testing) 
7  Pregnancy test and contraception check: Serum or urine pregnancy test for females of childbearing potential. Follicle stimulating hormone test may be 
performed for post-menopausal women. Contraception use will be checked to confirm that contraception is used consistently and correctly. 
8  Reflex auto-antibodies will be evaluated in case of suspected ALLO-647 treatment emergent autoimmunity AE. Depending on the type of AE, the tests 
should include (but not limited to) serum antiphospholipid antibodies (APA), platelet-bound APA, anti-Factor VIII antibodies, anti-Thyroid Peroxidase (anti-
TPO), anti-Thyroglobulin (anti-TG) and anti-thyroid stimulating hormone (anti-TSH receptor), Coombs test, antinuclear antibodies (ANA), perinuclear anti-
neutrophil cytoplasmic antibodies (P-ANCA), anti-neutrophil cytoplasmic antibodies (cANCA), and/or anti-Sjogren’s syndrome type B (anti-SSB). 
9  EQ-5D-5L (PRO) and QLQ-C30 (PRO):  Not required after documented disease progression per Lugano criteria or initiation of subsequent anti-cancer 
therapy. 
10  PET/CT Lymphoma assessments by positron emission tomography (PET)/computerized tomography (CT): tumor assessments will include all known 
or suspected disease sites.  Disease-specific imaging as clinically appropriate will be performed as described in the study imaging manual. Radiographic 
disease assessment will not be required after documented disease progression per Lugano criteria or initiation of subsequent anti-cancer therapy. 
11  Bone Marrow Biopsy and Aspirate: Bone marrow biopsy and aspirate will be completed at the time complete response (CR) is suspected only if bone marrow 
infiltration is positive or unknown at screening, and as clinically indicated. Samples (screening; others as indicated) will be banked, and may be analyzed for 
insertion site analysis, molecular analysis, and other similar analyses. Proceduralist should aim to achieve a 2cm core to best assess cellularity. Not required 
after documented disease progression per Lugano criteria or initiation of subsequent anti-cancer therapy. 
12  Lymph node biopsy: To be performed as clinically indicated. Not required after documented disease progression per Lugano criteria or initiation of 
subsequent anti-cancer therapy. 
13  Follow-up for survival: All randomized subjects will be followed in the follow-up period for survival and disease status. As part of the study sites may be asked 
to conduct searches of public records, such as those establishing survival status, if available, to obtain survival data if the subject survival status is not already 
known. Sites may be also asked to also retrieve autopsy reports to confirm status of disease at the time of death and as per FDA Guidance: Testing of Retroviral 
Vector-Based Human Gene Therapy Products for Replication Competent Retrovirus During Product Manufacture and Patient Follow-up (July 2018) 
14  Replication competent lentivirus (RCL): Whole blood samples will be collected to monitor for the presence of RCL-specific DNA sequences by a 
validated PCR-based assay.  Samples may be analyzed for RCL only 
; if negative, then remaining samples 
 may be 
collected and archived.  Assess for RCL upon diagnosis of a new (secondary) malignancy.   
15  Genomic safety biospecimen: Unless prohibited by local regulations or ethics committee decision, a blood sample will be collected during 
 and every 
, for assays related to treatment response in the disease under study, eg, insertion site analysis, malignancy panels, etc.  
16  PBMCs: Peripheral blood mononuclear cells (PBMCs) will be collected at the indicated timepoints and cryopreserved for future cytogenetics, cellular, 
molecular or proteomic studies.  
 
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INVESTIGATOR SIGNATURE PAGE 
 
Allogene Therapeutics 
 
 
 
A Randomized, Open-label, Phase 2 Study Evaluating Lymphodepletion with Fludarabine, 
Cyclophosphamide, and ALLO-647, vs Fludarabine and Cyclophosphamide alone, in 
Subjects with Relapsed/Refractory Large B-cell Lymphoma (LBCL) Receiving 
ALLO-501A Allogeneic CAR T Cell Therapy 
 
 
 
Protocol Number:   
ALLO-647-201 
Protocol Date:  
13 October 2022 
Protocol Version: 
Amendment 1 
 
Signature of Agreement for Protocol ALLO-647-201 (EXPAND Study) 
I have read this protocol and agree to conduct the study as outlined herein, in 
accordance with all applicable regulations including the International Conference on 
Harmonization guidelines on Good Clinical Practices (ICH-E6). 
 
 
_______________ 
 
_______________________________________ 
Site Number  
 
Print Site Name 
 
____________________________________________ 
_______________ 
Investigator Signature  
 
 
 
 
Date 
 
____________________________________________ 
Print Investigator Name and Title 
 
 
  
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