Clinical trial NCT05296525
Conditions: Non-Hodgkin Lymphoma
Keywords: lymphoma GDA-201 NK cells rituximab Lymphoma, B-Cell Lymphoma, Large B-Cell, Diffuse
Sponsor: Gamida Cell ltd
Start date: 2022-07-05; Completion date: 2024-04-22
Enrollment: 13 participants; Allocation: NON_RANDOMIZED; Intervention model: SEQUENTIAL

Brief summary:
This is an open-label, non-randomized, interventional, single group assignment study of GDA-201, an allogeneic cryopreserved Natural Killer (NK) cell therapy derived from donor peripheral blood, in combination with rituximab, monoclonal anti-CD20 antibody, for patients with relapsed or refractory B Cell non-Hodgkin lymphoma (NHL).

Detailed description:
The study is divided into a phase I dose escalation phase and a phase II expansion phase.

Patients with relapsed or refractory follicular lymphoma (FL) or diffuse large B-cell lymphoma (DLBCL)/high grade B-cell lymphoma (HGBCL) will receive GDA-201 followed by a short course of low-dose interleukin-2 (IL-2). Rituximab will be administered prior to and after GDA-201 infusion.

Phase I: Dose escalation phase The objective of Phase I is to evaluate the safety of GDA-201 in patients with FL, DLBCL/ HGBCL, marginal zone lymphoma or mantle cell lymphoma. The maximal tolerated dose (MTD) and recommended Phase II Dose (RP2D) will be determined based on dose limiting toxicities (DLT).

Phase II expansion phase The objective of the Phase II expansion cohort is to evaluate the safety and efficacy of GDA-201 in two patient cohorts, FL and DLBCL/HGBCL.

Arms: arm 1: Dose escalation with up to 4 dose levels to reach MTD and determine recommended Phase II dose (RP2D). arm 2: RP2D will be administered to all patients.
Interventions: intervention 1: GDA-201
Intervention descriptions: intervention 1: NAM-expanded allogeneic NK cells

Protocol documents:
Prot_SAP_001.pdf: 
 
GC P#01.01.050 GDA-201 Phase I/II Protocol Amendment II       Date: May 02, 2023 
 
 
 
 
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CLIENT CONFIDENTIAL 
PROTOCOL 
 
Study Title 
A Phase I/II Multicenter Study Evaluating the Safety and 
Efficacy of Allogeneic GDA-201 Natural Killer Cells in 
Patients with Relapsed/Refractory B Cell Non-Hodgkin 
Lymphoma 
 
Brief Title 
 
Evaluation of Safety and Efficacy of GDA-201 NK Cells 
in Patients With Relapsed/Refractory B Cell NHL 
Clinical Phase 
Phase I/II 
Product 
GDA-201 
IND Number 
 
EU Trial Number 
 
2023-503432-41-00 
 
Sponsor 
Gamida Cell Ltd. 
Beit Ofer 
5 Nahum Hafzadi 
Jerusalem 9548401 
Israel 
 
Tel: 972-2-6595666 
Medical Director  
Roei Mazor, M.D., PhD 
Protocol No.
 
 
GC P#01.01.050 
Amendment 
# II 
Dated
 
 
May 02, 2023 
This clinical study will be conducted in accordance with the Sponsor's Standard Operating Procedures 
(SOPs), this protocol, current Good Clinical Practice (GCP), the Declaration of Helsinki, the 
provisions of International Conference on Harmonization (ICH) Guidelines, Regulation (EU) No 
536/2014 and all local applicable laws and regulations. 
 
CONFIDENTIAL 
The information in this document is considered privileged and confidential and may not be disclosed 
to others except to the extent necessary to obtain Institutional Review Board (IRB)/ Ethics Committee 
(EC) approval, written informed consent and the approval of local regulatory authorities as required 
by local law. 
 


 
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CLIENT CONFIDENTIAL 
TABLE OF CONTENTS 
TABLE OF CONTENTS ................................................................................................................ 2 
LIST OF TABLES .......................................................................................................................... 8 
LIST OF FIGURES ......................................................................................................................... 9 
LIST OF ABBREVIATIONS ....................................................................................................... 10 
SPONSOR PROTOCOL APPROVAL PAGE ............................................................................. 12 
INVESTIGATOR’S AGREEMENT ............................................................................................ 13 
1. 
STUDY SYNOPSIS .................................................................................................. 14 
2. 
INTRODUCTION ..................................................................................................... 29 
2.1. 
Overview .................................................................................................................... 29 
2.1.1. 
Non-Hodgkin Lymphoma .......................................................................................... 29 
2.2. 
Gamida Cell Nicotinamide (NAM) Technology........................................................ 31 
2.2.1. 
Background to NK Cells ............................................................................................ 31 
2.2.2. 
Nicotinamide (NAM) based technology .................................................................... 32 
2.2.3. 
Summary of previous human study ........................................................................... 33 
2.3. 
Overall Risk Benefit ................................................................................................... 36 
2.4. 
Rationale for Study Design & Dosages ..................................................................... 36 
2.4.1. 
Study Population ........................................................................................................ 36 
2.4.2. 
Dosage GDA-201 ....................................................................................................... 37 
2.4.3. 
Host Conditioning ...................................................................................................... 37 
3. 
STUDY OBJECTIVES, HYPOTHESIS & STUDY ENDPOINTS .......................... 40 
3.1. 
Objectives ................................................................................................................... 40 
3.1.1. 
Study Hypothesis ....................................................................................................... 40 
3.1.2. 
Study Objectives ........................................................................................................ 40 
3.2. 
Study Endpoints ......................................................................................................... 40 
3.2.1. 
Primary Endpoints ...................................................................................................... 40 
3.2.2. 
Secondary Endpoints .................................................................................................. 40 
3.2.3. 
Exploratory Endpoints ............................................................................................... 40 
4. 
STUDY POPULATION ............................................................................................ 41 
4.1. 
Number of Patients ..................................................................................................... 41 
4.2. 
Eligibility Criteria ...................................................................................................... 41 


 
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CLIENT CONFIDENTIAL 
4.2.1. 
Inclusion Criteria ........................................................................................................ 41 
4.2.2. 
Exclusion Criteria....................................................................................................... 42 
5. 
PATIENT ENROLLMENT & DOSE LEVEL ASSIGNMENT ............................... 44 
5.1. 
Written Consent ......................................................................................................... 44 
5.2. 
GDA-201 Cell Dose Level Assignment ..................................................................... 44 
5.2.1. 
Patients Who Do Not Begin Study Treatment ........................................................... 44 
5.3. 
Patient Enrollment ...................................................................................................... 44 
6. 
STUDY TREATMENT ............................................................................................. 45 
6.1. 
Treatment Plan ........................................................................................................... 45 
6.1.1. 
Phase I: Dose Escalation ............................................................................................ 45 
6.1.2. 
Phase II: Expansion Phase ......................................................................................... 46 
6.2. 
Treatment Regimen .................................................................................................... 47 
6.2.1. 
Rituximab ................................................................................................................... 47 
6.2.2. 
Investigational Product GDA-201.............................................................................. 47 
6.2.3. 
Interleukin-2 ............................................................................................................... 49 
6.2.4. 
Lymphodepleting (LD) Chemotherapy ...................................................................... 50 
6.2.5. 
Concomitant Therapy for Symptom Management ..................................................... 51 
6.2.6. 
Concomitant Medications .......................................................................................... 51 
7. 
STUDY VISITS AND PROCEDURES .................................................................... 52 
7.1. 
Study Procedures ........................................................................................................ 52 
7.1.1. 
Informed Consent ....................................................................................................... 52 
7.1.2. 
Demographic Data ..................................................................................................... 52 
7.1.3. 
Medical and Previous Cancer Treatment History ...................................................... 52 
7.1.4. 
Physical Exam, Vital Signs and ECOG Performance Status ..................................... 52 
7.1.5. 
Cardiac Function ........................................................................................................ 53 
7.1.6. 
Disease Response Assessment ................................................................................... 53 
7.1.7. 
Laboratory .................................................................................................................. 54 
7.2. 
Study Visits ................................................................................................................ 54 
7.2.1. 
Study Duration ........................................................................................................... 54 
7.2.2. 
Screening .................................................................................................................... 55 
7.2.3. 
Study Visit Day -10 .................................................................................................... 57 


 
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CLIENT CONFIDENTIAL 
7.2.4. 
Study Visit Day -5, Day -4 and Day -3 ...................................................................... 57 
7.2.5. 
Study Visit Day 0 ....................................................................................................... 58 
7.2.6. 
Study Visit Day 2 ....................................................................................................... 58 
7.2.7. 
Study Visit Day 4 ....................................................................................................... 59 
7.2.8. 
Study Visit Day 7 ....................................................................................................... 59 
7.2.9. 
Study Visit Day 14 ..................................................................................................... 60 
7.2.10. 
Study Visit Day 21 ..................................................................................................... 60 
7.2.11. 
Study Visit Day 28 ..................................................................................................... 60 
7.2.12. 
Study Visit Day 42 ..................................................................................................... 61 
7.2.13. 
Study Visit Day 56 ..................................................................................................... 61 
7.2.14. 
Study Visit Day 70 ..................................................................................................... 61 
7.2.15. 
Study Visit Days 90, 120, 180, 270 and 365 .............................................................. 62 
7.2.16. 
Termination Visit ....................................................................................................... 62 
7.3. 
Long Term Follow-Up (LTFU) ................................................................................. 63 
8. 
STUDY MEDICATION: GDA-201 .......................................................................... 64 
8.1. 
Description ................................................................................................................. 64 
8.2. 
Manufacturing and Shipping ...................................................................................... 64 
8.3. 
GDA-201 Supply ....................................................................................................... 64 
8.4. 
Handling and Preparation of GDA-201 ..................................................................... 64 
8.5. 
Administration ........................................................................................................... 65 
9. 
STUDY STEERING COMMITTEE (SSC) .............................................................. 66 
10. 
DISCONTINUATION, TERMINATION OR COMPLETION OF STUDY ........... 67 
10.1. 
Study Discontinuation ................................................................................................ 67 
10.2. 
Study Termination ...................................................................................................... 67 
10.2.1. 
Subject Withdrawal .................................................................................................... 67 
10.2.2. 
Lost to follow-up ........................................................................................................ 67 
10.2.3. 
If a patient does not respond within 1 month after the second contact the patient 
will be considered lost to follow-up and no additional contact will be 
requiredStudy Completion ......................................................................................... 68 
10.2.4. 
Termination Visit ....................................................................................................... 68 
11. 
TERMINATION VISIT WILL INCLUDE ALL RELEVANT STUDY 
ASSESSMENTS (SEE SECTION 7.2.16) NOT EVALUATED WITHIN 2 


 
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CLIENT CONFIDENTIAL 
WEEKS PRIOR TO THE SUBJECT TERMINATION. SAFETY 
EVALUATIONS AND CRITERIA .......................................................................... 69 
11.1. 
Safety Evaluation and Dose Escalation...................................................................... 69 
11.2. 
Dose-Limiting Toxicity Definition ............................................................................ 69 
11.3. 
Continuation of Therapy ............................................................................................ 69 
11.4. 
Dose Modifications and Discontinuations Due to Toxicity ....................................... 70 
11.5. 
Management of Expected Toxicities Associated with GDA-201 Infusion and 
IL-2 ............................................................................................................................. 70 
11.5.1. 
Expected Toxicities .................................................................................................... 70 
11.5.2. 
Management of Expected GDA-201 Toxicities ......................................................... 71 
11.5.3. 
Management of IL-2 Toxicity .................................................................................... 72 
12. 
STATISTICAL CONSIDERATIONS ....................................................................... 73 
12.1. 
Design and Sample Size Considerations .................................................................... 73 
12.2. 
Study Endpoints ......................................................................................................... 73 
12.2.1. 
Primary Endpoints ...................................................................................................... 73 
12.2.2. 
Secondary Endpoints .................................................................................................. 74 
12.2.3. 
Exploratory Endpoints ............................................................................................... 74 
12.3. 
Analysis Population ................................................................................................... 74 
12.4. 
Patient Disposition ..................................................................................................... 74 
12.5. 
Baseline Characteristics ............................................................................................. 74 
12.6. 
Safety Analysis .......................................................................................................... 75 
12.6.1. 
Safety Alert Criteria ................................................................................................... 75 
12.6.2. 
Analysis of AEs and Laboratory Values .................................................................... 75 
12.7. 
Efficacy Analysis ....................................................................................................... 76 
12.8. 
Timing of analyses ..................................................................................................... 76 
12.9. 
Long Term Follow Up ............................................................................................... 77 
12.10. 
End of Study ............................................................................................................... 77 
13. 
TUMOR DEFINITIONS AND ASSESSMENT ....................................................... 78 
13.1. 
Metabolic Criteria ...................................................................................................... 78 
13.1.1. 
Complete Response (CR) ........................................................................................... 78 
13.1.2. 
Partial Response (PR) ................................................................................................ 78 
13.1.3. 
Stable Disease ............................................................................................................ 78 


 
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CLIENT CONFIDENTIAL 
13.1.4. 
Progressive Disease (after Partial Response, Stable Disease), Relapsed Disease 
(after Complete Response) ......................................................................................... 78 
13.2. 
Radiographic Response Criteria ................................................................................. 78 
13.2.1. 
Complete Response .................................................................................................... 79 
13.2.2. 
Partial Response ......................................................................................................... 79 
13.2.3. 
Stable Disease ............................................................................................................ 79 
13.2.4. 
Progressive Disease (after Partial Response, Stable Disease), Relapsed Disease 
(after Complete Response) ......................................................................................... 79 
13.3. 
Definitions .................................................................................................................. 80 
14. 
TREATMENT COMPLIANCE................................................................................. 81 
15. 
ASSESSMENT OF SAFETY .................................................................................... 82 
15.1. 
Relationship to Study Drug ........................................................................................ 82 
15.1.1. 
Adverse Event (AE) ................................................................................................... 82 
15.1.2. 
Serious Adverse Event (SAE) .................................................................................... 82 
15.1.3. 
Unexpected Adverse Event (AE) ............................................................................... 82 
15.1.4. 
Relationship of Adverse Events (AEs) to Study Drug ............................................... 83 
15.1.5. 
AE Severity ................................................................................................................ 83 
15.2. 
Grade refers to the severity of the AE. The CTCAE displays Grades 1 through 5 
with unique clinical descriptions of severity for each AE based on general 
guideline described in CTCAE version 5.0.Procedures for Adverse Event (AE) 
Recording and Reporting ........................................................................................... 83 
15.3. 
Other Required Safety Assessments .......................................................................... 84 
15.4. 
Pregnancy ................................................................................................................... 85 
15.4.1. 
Pregnancy Reporting .................................................................................................. 85 
15.4.2. 
Females of Childbearing Potential and Contraception............................................... 85 
16. 
SPECIAL REQUIREMENTS AND PROCEDURES ............................................... 87 
16.1. 
Study Monitoring ....................................................................................................... 87 
16.1.1. 
Audits and Inspections ............................................................................................... 87 
16.1.2. 
Data Quality Control and Quality Assurance ............................................................ 87 
16.2. 
Confidentiality ........................................................................................................... 87 
16.2.1 Publication Policy .............................................................................................................. 88 
16.3. 
Protocol Amendments ................................................................................................ 88 
16.4. 
Obligations of the Principal Investigator ................................................................... 88 


 
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CLIENT CONFIDENTIAL 
16.4.1. 
Institutional Review Board (IRB)/Independent Ethics Committee (IEC) ................. 88 
16.4.2. 
Ethical Conduct of the Study ..................................................................................... 88 
16.4.3. 
Written Informed Consent ......................................................................................... 89 
16.4.4. 
Patient Data Protection ............................................................................................... 89 
17. 
DATA HANDLING AND RETENTION OF RECORDS ........................................ 90 
17.1. 
Electronic Case Report Form Completion ................................................................. 90 
17.2. 
Retention of Records .................................................................................................. 90 
18. 
REFERENCES ........................................................................................................... 91 
APPENDIX A. PERFORMANCE STATUS SCALE AND NYHA CLASSIFICATION ........ 96 
APPENDIX B. INFECTIOUS DISEASES SOCIETY OF AMERICAS (IDSA) 
GUIDELINES ON CLEARANCE OF HEPATITIS B AND C INFECTION .......... 97 
APPENDIX C. DEFINITIONS OF TUMOR RESPONSE (LUGANO, 2014) ......................... 98 
APPENDIX D. GVHD ASSESSMENT .................................................................................. 100 
APPENDIX E. EXPECTED TOXICITIES OF STUDY MEDICATION ............................... 102 
APPENDIX F. THE COMMON TERMINOLOGY CRITERIA FOR ADVERSE 
EVENTS (CTCAE)  VERSION 5.0 ........................................................................ 107 
 
 
 


 
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CLIENT CONFIDENTIAL 
LIST OF TABLES 
Table 1: 
Schedule of Events ..................................................................................................... 26 
Table 2:  
GDA-201 Dose Cohorts in Study MT2015-46 .......................................................... 34 
Table 3: 
Dosing Cohorts .......................................................................................................... 45 
Table 4: 
Study Treatment Plan ................................................................................................. 47 
Table 5: 
GDA-201 Dosing Table ............................................................................................. 49 
Table 6: 
GDA-201 Dose Modifications and Discontinuations for Possibly Related 
Toxicities .................................................................................................................... 70 
Table 7: 
 Alert threholds based on Grade III-IV acute GvHD ................................................. 75 
Table 8: 
GvHD classification ................................................................................................. 100 
Table 9: 
Clinical manifestations and staging of acute graft versus host disease .................... 100 
Table 10: NIH Global Severity of chronic GvHD ................................................................... 101 
 


 
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CLIENT CONFIDENTIAL 
LIST OF FIGURES 
Figure 1: 
Study Design Schema ................................................................................................ 24 
Figure 2: 
Patient Treatment & Follow-up Schema .................................................................... 25 
Figure 3: 
Responses of NHL Patients in Study MT2015-46 ..................................................... 35 
Figure 4: 
Percentage of Donor-HLA-positive NK cells in peripheral blood in Study 
MT2015-46 (n=15) .................................................................................................... 35 
 


 
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CLIENT CONFIDENTIAL 
LIST OF ABBREVIATIONS 
aGvHD 
acute graft-versus-host disease 
ACT 
adoptive cell therapy 
ADC 
Antibody-Drug Conjugate 
AE 
adverse event 
ALT 
alanine aminotransferase 
ANC 
absolute neutrophil count 
ASCT 
autologous stem cell transplantation  
AST 
aspartate aminotransferase 
BITE 
Bispecific T cell Engager 
CAR-T 
chimeric antigen receptor modified T-cells 
CLL 
chronic lymphocytic leukemia 
CNS 
central nervous system 
CR 
complete response 
CRu 
complete response/unconfirmed 
CSF  
cerebrospinal fluid 
CT 
computed tomography 
DLBCL 
diffuse large B-cell lymphoma 
DLT 
dose-limiting toxicity 
DM 
 
diabetes mellitus 
ECG 
electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
FDA 
Food and Drug Administration 
FDG-PET 
fluorodeoxyglucose-positron emission tomography 
FFPE 
Formalin-Fixed Paraffin-Embedded 
FL 
follicular lymphoma 
GCP 
good clinical practice 
GTD 
greatest transverse diameter  
GvHD 
graft-versus-host disease 
HbsAg 
hepatitis B surface antigen 
HBV 
hepatitis B virus 
HGBCL 
high-grade B-cell lymphoma 
HGBCL NOS 
high-grade B-cell lymphoma not otherwise specified 
HIV 
human immunodeficiency virus 
HSCT 
hematopoietic stem cell transplantation 
IDSA 
Infectious Diseases Society of America 
IRB 
institutional review board 
IEC 
independent ethics committee 


 
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CLIENT CONFIDENTIAL 
ICF 
informed consent form 
IV 
intravenous 
LD 
lymphodepletion 
LN 
lymph nodes 
mAb 
monoclonal antibody 
MM 
Multiple myeloma 
MRI 
magnetic resonance imaging 
MTD 
maximum tolerated dose 
NAM 
nicotinamide  
NCI-CTCAE 
National Cancer Institute Common Terminology Criteria for 
Adverse Events 
NHL 
non-Hodgkin lymphoma 
NK 
natural killer 
ORR 
overall response rate 
PMBCL 
primary mediastinal B-cell lymphoma  
PD 
progressive disease 
PET 
positron emission tomography 
PK 
pharmacokinetics 
PR 
partial response 
PT 
preferred term 
RCT 
randomized clinical trial 
RP2D 
recommended phase II dose 
SAE 
serious adverse event 
SC 
Subcutaneous/subcutaneously 
SD 
stable disease 
SLL 
small lymphocytic lymphoma  
SOC 
system organ class 
SOE 
schedule of events 
SPD 
sum products of the greatest diameters 
SSC 
study steering committee 
TBili 
total bilirubin 
ULN 
upper limit of normal 
UTI 
urinary tract infection 
WBC 
white blood cell 


 
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CLIENT CONFIDENTIAL 
SPONSOR PROTOCOL APPROVAL PAGE 
 
Protocol Title:  
A Phase I/II Multicenter Study Evaluating the Safety and Efficacy of 
Allogeneic GDA-201 Natural Killer Cells in Patients with 
Relapsed/Refractory B Cell Non-Hodgkin Lymphoma 
 
 
Clinical Phase 
 
Phase I/II 
 
Protocol Number:   
GC P#01.01.050 
Amendment Number: 
Amendment II 
Dated:  
 
 
May 02, 2023 
 
 
Approved by: 
 
Medical Director 
 
 
 
 
 
___________________________________  
___________________________ 
Signature  
 
 
 
 
 
Date 


 
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                                                          Page 13 of 108 
 
CLIENT CONFIDENTIAL 
INVESTIGATOR’S AGREEMENT 
 
Protocol Title:  
A Phase I/II Multicenter Study Evaluating the Safety and Efficacy of 
Allogeneic GDA-201 Natural Killer Cells in Patients with 
Relapsed/Refractory B Cell Non-Hodgkin Lymphoma 
 
Clinical Phase: 
 
Phase I/II 
Protocol Number: 
 
GC P#01.01.050 
Amendment Number: 
Amendment II 
Dated:  
 
 
May 02, 2023 
 
I have carefully read the foregoing protocol including all appendices and agree that it contains all the 
necessary information for conducting the study safely. 
I will conduct this study in strict accordance with this protocol and according to the current Good 
Clinical Practice (GCP) regulations and will attempt to complete the study within the time designated. 
I will provide copies of the protocol and all other information relating to pre-clinical and prior clinical 
experience submitted by the sponsor to all personnel responsible to me who participate in the study. 
I will discuss this information with them to ensure that they are adequately informed regarding the 
drug and conduct of the study. 
I agree to keep records on all patient information (CRFs, shipment, and all other information collected 
during the study) in accordance with the current GCP and local regulations. 
 
Principal Investigator’s Name 
 
Signature 
 
Date 
 
Institution 
 
 


 
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CLIENT CONFIDENTIAL 
1. 
STUDY SYNOPSIS 
Protocol Number 
GC P#01.01.050 
Protocol Title  
A Phase I/II Multicenter Study Evaluating the Safety and Efficacy of Allogeneic 
GDA-201 Natural Killer Cells in Patients with Relapsed/Refractory B Cell Non-
Hodgkin Lymphoma 
Brief Title 
Evaluation of Safety and Efficacy of GDA-201 NK Cells in Patients With 
Relapsed/Refractory B Cell NHL 
Principal Investigator: 
 
Sponsor:   
Gamida Cell  
Beit Ofer, 5 Nahum Hafzadi 
Givat Shaul, Jerusalem, 9548401 
Israel 
IND Number: 
 
EU Trial Number 
2023-503432-41-00 
Number of Centers 
Multicenter (Phase I in US; Phase II in US, Israel, and Europe) 
Clinical Phase 
Phase I/II 
Investigational Product   GDA-201 is an allogeneic cryopreserved natural killer (NK) cell-based therapy 
derived from donor peripheral blood  
Study Duration  
 
Total study duration for individual patients is approximately 13 months from the 
signing of informed consent to the last visit (one year following the first GDA-
201 infusion). The study ends when all patients have completed their last follow-
up. Patients who enroll in the long-term follow up sub-study will be followed 
for an additional 5 years, up to 6 years following the initial GDA-201 infusion.  
Study Objectives  
 
The overall study objective is to evaluate the safety and efficacy of 
cryopreserved, allogeneic GDA-201 in patients with relapsed/refractory B Cell 
Non-Hodgkin Lymphoma (NHL).  
Phase I objectives: 
• Assess the safety of GDA-201 + rituximab as determined by dose limiting 
toxicities 
• Determine the maximum tolerated dose (MTD), to be applied as the 
recommended Phase II dose (RP2D) 
 
Phase II objectives: 


 
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CLIENT CONFIDENTIAL 
• Assess the safety and efficacy of GDA-201 in separate cohorts of patients 
with follicular lymphoma (FL), or diffuse large B-cell lymphoma (DLBCL) 
and High grade B cell lymphoma (HGBCL)  
Primary Study 
Endpoints 
Primary endpoint- Phase I: 
• dose-limiting toxicity (DLT) and safety of GDA-201 
Primary endpoint: Phase II: 
• Overall response rate (ORR) 
Secondary and 
Exploratory Study 
Endpoints 
Secondary endpoints: Phase I: 
• ORR  
Secondary endpoints: Phase II: 
• ORR Independent Radiological Review Committee (IRRC) 
• Duration of response (DOR) (Investigator Assessment) 
• Progression free survival (PFS) (Investigator Assessment) 
• Overall survival (OS) (Investigator Assessment) 
• Safety and tolerability (Investigator Assessment) 
Exploratory Endpoints 
 
 
 
 
 
Study Hypothesis 
Infusion of GDA-201 in patients with relapsed/refractory NHL will be safe and 
provide a disease response. 
Number of Patients  
 
A maximum of 99 patients will be treated as follows: 
12-36 patients in the Phase I portion 
63 patients (32 in FL cohort and 31 in DLBCL/HGBCL cohort) in the Phase II 
portion   
Inclusion Criteria 
 
1. Patients must have relapsed/refractory FL or DLBCL/HGBCL that has 
failed conventional therapy defined as follows (for the Phase I dose 
escalation: patients with marginal zone lymphoma or mantle cell 
lymphoma are also eligible): 
a. Lymphoma characterized by current and/or historical expression 
of 
CD20 
as 
determined 
by 
flow 
cytometry 
or 
immunohistochemistry. 
b. Received at least 2 prior lines of therapy (at least one of which 
contained chemotherapy and at least one of which contained an 
anti-CD20 monoclonal antibody (mAb)).  


 
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CLIENT CONFIDENTIAL 
c. Transplant ineligible patients allowed assuming they meet 
criterion b. 
  
d. Patients who failed prior chimeric antigen receptor modified T 
cells (CAR-T) cell therapy or are considered ineligible for CAR-
T therapy per the Investigator's discretion are eligible.  
e. FL transformed to DLBCL/HGBCL: Must have received at least 
1 line of therapy after transformation to DLBCL/HGBCL 
2. Patients must have measurable disease as defined by the Lugano 
response criteria (Cheson et al. 2014) as determined by study 
investigators. Lesions that have been previously irradiated will be 
considered measurable only if progression has been documented 
following completion of radiation therapy. Baseline disease assessment 
must be performed after completion of the last line of therapy. 
3. Patients must be at least 18 years of age. In Dose level 1 patients must 
be at least 75 kg. 
4. Patients must have Eastern Cooperative Oncology Group (ECOG) 
performance status 0 or 1  
5. Patients must have adequate hematologic, hepatic, renal, cardiac and 
pulmonary function prior to any study treatment defined as: 
a. Absolute neutrophil count (ANC) ≥ 1000/μL 
b. Platelet count ≥ 50,000/μL  
c. Creatinine ≤ 1.5 mg/dL or creatinine clearance ≥50 mL/min  
d. Serum 
alanine 
aminotransferase 
(ALT) 
or 
aspartate 
aminotransferase (AST) ≤ 3 x upper limit of normal (ULN) 
e. Total bilirubin (TBili) ≤ 1.5 x ULN unless patient with a history 
of Gilbert’s syndrome 
f. Cardiac ejection fraction ≥ 45%, no evidence of pericardial 
effusion as determined by an echocardiography 
g. Baseline oxygen saturation > 92% on room air 
h. No clinically significant pleural effusion 
If organ dysfunction is due to lymphoma involvement and not due to prior 
toxicities the following laboratory parameters are permitted: 
 
a. Platelet count ≥ 30,000 if due to hypersplenism or disease 
involvement in marrow 
b. TBili ≤ 3 x ULN if due to hepatic disease involvement 
c.  Growth factors are permitted to meet required ANC if cytopenia 
is due to marrow disease involvement 
6. No Class II or greater New York Heart Association Functional 
Classification criteria (Appendix A) or serious cardiac arrhythmias 
likely to increase the risk of cardiac complications of cytokine therapy 
(e.g. 
ventricular 
tachycardia, 
frequent 
ventricular 
ectopy, 
or 
supraventricular tachyarrhythmia requiring chronic therapy)  


 
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7. Patients must be able to be off systemic corticosteroids (with the 
exception of physiological steroid replacement therapy) and other 
immunosuppressive drugs for at least 5 half-lives prior to GDA-201 
infusion and up until day 14 post GDA-201 infusion (excluding 
preparative regimen pre-medications), unless approved by the sponsor. 
8. Patients after allogeneic Hematopoietic Stem Cell Transplantation )HSCT ( 
are eligible if they are at least 6 months after the transplant and off all 
immunosuppressive drugs . 
9. Patients after allogeneic HSCT or any other allogeneic cell therapy are 
eligible without evidence of active Graft-versus-Host Disease (GvHD). 
10. No evidence of ongoing neurotoxicity or cytokine release syndrome 
from prior therapies 
11. Sexually active females of childbearing potential and males with 
partners of childbearing potential must agree to use effective 
contraception from the time of screening pregnancy test  and for at least 
4 months after completion of therapy 
12. Patient signs the written informed consent after being aware of the nature 
of the patient’s disease and willingly consents to the treatment program 
after being informed of alternative treatments, potential risks, benefits, 
and discomforts 
Exclusion Criteria 
 
1. Pregnancy, as indicated by a positive serum or urine human chorionic 
gonadotrophin (HCG) test, or lactation 
2. Active bacterial, fungal, or viral infection that is uncontrolled or 
requiring systemic antimicrobials for management. Simple urinary tract 
infection (UTI) and uncomplicated bacterial pharyngitis are permitted if 
responding to active treatment 
3. HIV infection not controlled on therapy, and/or with active viremia (HIV 
viral load needs to be undetectable), or  AIDS defining illnesses. 
4. History of acute or chronic active hepatitis B or C infection not 
documented to be cleared per current Infectious Diseases Society of 
America (IDSA) guidelines (see Appendix B). Patients at risk for 
reactivation of HBV infection must be on prophylactic anti-HBV 
antiviral therapy 
5. Patients with active autoimmune disease requiring immunosuppressive 
therapy. Patients with a history of autoimmune-related hypothyroidism 
on a stable dose of thyroid replacement hormone and patients with 
controlled type 1 diabetes mellitus (DM) on a stable insulin regimen may 
be eligible for this study. 
6. History of severe asthma and currently treated with chronic asthma 
medications (a history of mild asthma requiring inhaled steroids only is 
eligible) 
7. Live vaccine <6 weeks prior to start of therapy 
8. Patient with detectable cerebrospinal fluid (CSF) malignant cells, or 
brain metastases, or with a history of central nervous system (CNS) 
lymphoma or primary CNS lymphoma, CSF malignant cells or brain 


 
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CLIENT CONFIDENTIAL 
metastases. Patients with a history of CNS involvement can be included 
if cleared by magnetic resonance imaging (MRI) and CSF for at least 6 
months 
9. History of malignancy other than nonmelanoma skin cancer or 
carcinoma in situ (e.g. cervix, bladder, breast, prostate) unless disease 
free for at least 2 years 
10. Presence of any indwelling line or drain (e.g., percutaneous nephrostomy 
tube, 
indwelling 
foley 
catheter, 
biliary 
drain, 
or 
pleural/peritoneal/pericardial catheter). Dedicated central venous access 
catheters such as a Port-a-Cath or Hickman catheter are permitted 
11. History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., 
bronchiolitis 
obliterans), 
drug-induced 
pneumonitis, 
idiopathic 
pneumonitis, or evidence of active pneumonitis per chest imaging at 
screening. History of radiation pneumonitis in the radiation field 
(fibrosis) is allowed 
12. Known hypersensitivity to any of the study treatments, gentamycin, 
albumin, DMSO or any other GDA-201 excipient 
Note: Infusion reactions with rituximab are common. Patients with a history 
of infusion reactions to rituximab that can be managed with recommended 
pre-medications should not be excluded 
13. Time between previous treatment and first dose of study treatment 
(rituximab):  
a. Allogeneic HSCT < 6 months prior to study treatment 
b. ASCT < 3 months prior to study treatment 
c. CAR-T < 2 months prior to study treatment 
d. Major surgery or chemotherapy < 4 weeks prior to study 
treatment (6 weeks for melphalan) 
e. Radiation therapy < 2 weeks prior to study treatment 
f. Monoclonal antibodies including checkpoint blockade < 2 weeks 
prior to study treatment (does not apply to rituximab). 
g. Antibody-Drug Conjugates (ADCs) including polatuzumab 
vedotin and loncastuximab tesirine < 4 weeks prior to study 
treatment, unless approved by the sponsor 
h. Targeted therapies, Bispecific T cell Engagers (BiTEs),  small 
molecule inhibitors or any investigational therapy within 5 half-
lives of the drug, unless approved by the sponsor 
Study Design  
 
This is an open-label, non-randomized, interventional, single group assignment 
study of GDA-201, an allogeneic cryopreserved NK cell therapy derived from 
donor peripheral blood, in combination with rituximab, monoclonal anti-CD20 
antibody, for patients with relapsed or refractory B Cell non-Hodgkin lymphoma 
(NHL). 
Lymphoma characterized by current and/or historical expression of CD20 as 
determined by flow cytometry or immunohistochemistry. 
 


 
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The study is divided into a phase I dose escalation phase and a phase II 
expansion phase.  
 
Patients with relapsed or refractory FL or DLBCL/HGBCL (for the Phase I dose 
escalation: patients with marginal zone lymphoma or mantle cell lymphoma are 
also eligible) will receive GDA-201 followed by a short course of low-dose 
interleukin-2 (IL-2). Rituximab will be administered prior to and after GDA-201 
infusion  
 
Phase I: Dose escalation phase 
The objective of Phase I is to evaluate the safety of GDA-201 in patients with 
follicular lymphoma (FL),  diffuse large B-cell lymphoma/high grade B-cell 
lymphoma (DLBCL/HGBCL), marginal zone lymphoma or mantle cell 
lymphoma. The maximal tolerated dose (MTD) Recommended Phase II Dose 
(RP2D) will be determined based on dose limiting toxicities (DLT). 
 
The starting dose will be 2.5 x 107 cells/kg. Patients within each cohort will be 
assessed for DLTs, and enrollment in each cohort will continue to occur 
sequentially until a MTD is reached. 
 
DLTs are defined as one of the following within the first 28 days of the first 
dose of GDA-201, as assessed by CTCAE v 5.0. Acute GvHD is assessed 
according to the Consensus Conference on Acute GvHD grading (Przepiorka et 
al. 1995): 
• Steroid refractory Grade II acute GvHD  
• Grade III or IV acute GvHD  
• Grade 4 infusion reaction  
• Grade 4 or 5 related adverse event (AE)  
• Grade 3 or above cardiac, central nervous system or pulmonary adverse 
event 
• Any Grade 3 or above non-hematologic adverse event that does not resolve 
to Grade 2 or below within 72 hours, with the exception of renal or hepatic 
adverse events which may take up to 7 days to resolve 
• Treatment emergent ≥Grade 3 autoimmune disorder 
• Grade 3 or above allergic reaction that does not recover to Grade 2 or 
below within 24 hours 
• Grade 4 cytopenia lasting beyond Day 42 (the 28-day DLT observation 
period will be extended to confirm). 
 
The first 3 patients enrolled at each dose level will be staggered to allow 
monitoring of each patient for DLTs for 28 days following the first GDA-201 
infusion. Thus, patients may be added to each dose level cohort after the 
preceding patient in the cohort has been observed for a minimum of 28 days. 
Dose escalation to the subsequent level can occur following discussion with the 


 
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Study Steering Committee (SSC) after the last patient on the current cohort has 
been observed a minimum of 28 days.  
 
Dosing Cohorts 
Dose Level 
Dose* 
1 
2.5x107 cells/kg 
2 
5x107 cells/kg 
3 
1x108 cells/kg 
4 
2x108 cells/kg 
*Based on dosing tables for GDA-201 product bags, allowing 
a maximal deviation of 33% from the intended dose. 
 
Phase II expansion phase 
The objective of the Phase II expansion cohort is to evaluate the safety and 
efficacy of GDA-201 in two patient cohorts, FL and DLBCL/HGBCL. 
 
 


 
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Study Treatments  
 
The following table summarizes the overall treatment regimen.  
 
Component  
Dose 
Days 
Rituximab 
 
 
-10, -3, +14*  
Lymphodepletion 
(LD)  
 
 
  
 
 
  
-5, -4, -3 
GDA-201 
 
0, +2 
Interleukin-2 
  
0, +2, +4. 
* The last rituximab dose may be administered +/- 2 days  
 
Statistical 
Considerations 
Design and Sample size considerations: 
 
The Phase I portion of the study is a conventional 3 + 3 design with four 
sequential dose cohorts. The first cohort will start at the 2.5x 107 cells/kg dose 
level. If all cohorts are completed, 24 patients will have been treated with a 
maximum of 6 patients per cohort. The goal is to determine the recommended 
phase II dose (RP2D) during the phase I portion of the study. Phase I patients 
who are not evaluable for DLT may be replaced.  
 
At the discretion of the study sponsor, after the dose escalation phase across the 
four dose levels is complete, up to an additional 12 patients may be treated to 
further characterize the DLT and safety profiles by histology (follicular 
lymphoma or DLBCL/HGBCL) at one or two dose levels prior to the phase II 
expansion. This will be designated as “backfilling” a cohort in order to ensure 
that the cohort enrolls a minimum of 3 patients per histology. With the addition 
of the additional patients enrolled in backfilled cohorts, the MTD and/or RP2D 
may be determined. The RP2D may be different by histology (follicular 
lymphoma or DLBCL/HGBCL).  
 
For each cohort in the Phase II portion of the study, a Simon’s optimal 2-stage 
design will be employed based on the ORR (CR or PR) endpoint.  
• 
In the FL cohort, 11 patients will be enrolled in the first stage. If ≥3 
patients achieve ORR, it will continue to enroll an additional 21 patients in the 
second stage for a total of 32 patients in the cohort. At the end of stage 2, if ≥10 
out of the 32 patients achieve ORR, it is considered promising for further 
evaluation. This design has 80% power to test the null hypothesis of 20% 
response rate against the alternative hypothesis of 40% with a 1-sided type 1 
error rate not exceeding 0.075 
• 
In the DLBCL/HGBCL cohort, 14 patients will be enrolled in the first 
stage. If ≥3 patients achieve ORR, it will continue to enroll an additional 17 
patients in the second stage for a total of 31 patients in the cohort. At the end of 


 
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                                                          Page 22 of 108 
 
CLIENT CONFIDENTIAL 
stage 2, if ≥8 out of the 31 patients achieve ORR, it is considered promising for 
further evaluation. This design has 80% power to test the null hypothesis of 15% 
response rate against the alternative hypothesis of 33% with a 1-sided type 1 
error rate not exceeding 0.075 
 
Phase II patients who are not evaluable for response may be replaced. Patients 
who have at least one efficacy evaluation following GDA-201 infusion will be 
considered evaluable for response. 
 
Safety Analysis 
The data emerging from this study will be reviewed periodically by the SSC and 
recommendations will be provided to the sponsor. 
Ongoing safety assessment guidelines will be used to monitor the following 
events, and alert the SSC. A safety alert will be triggered if one of the following 
criteria is met: 
1. Any death not related to disease progression 
2. Grade 4 or above cardiac, CNS or pulmonary DLT in 2 subjects, that is 
at least possibly related to GDA-201 
3. Any DLT occurring in Dose level 1 
4. Grade 5 adverse event that is probably or directly related to GDA-201 
5. Grade III-IV acute GvHD crossing the thresholds based on a Bayesian 
continuous monitoring model detailed in 12.6.  
 
If an alert occurs, accrual to the study will be temporarily halted. The SSC will 
consider the data in depth and make recommendations to the sponsor. 
 
All adverse events (AEs) will be coded to a system organ class (SOC) and a 
preferred term (PT) based on the Medical Dictionary for Regulatory Activities 
(MedDRA) version 21.0 or later.  
Patient incidence of all adverse events (AEs), serious adverse events (SAEs), 
AEs leading to discontinuation of treatment, and fatal AEs will be tabulated by 
SOC and PT. 
The number and percent of patients reporting AEs will be evaluated overall and 
by dose level and will also be tabulated by severity and relationship to study 
treatment. The severity of each AE will be graded using The Common 
Terminology Criteria for Adverse Events (CTCAE) v 5.0 or later criteria. 
For the Phase I portion of the study, DLTs (if any) will be summarized by dose 
and will be listed separately.  
Changes in laboratory values and vital signs will be summarized with 
descriptive statistics. Use of concomitant medications, levels of GDA-201 cells 
in blood and incidence of anti-HLA antibodies will also be summarized. 
 
 
Efficacy Analysis 
 


 
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                                                          Page 23 of 108 
 
CLIENT CONFIDENTIAL 
The primary analysis for efficacy will be based on the cohort-specific efficacy 
evaluable analysis population. Sensitivity analyses may include pooling 
additional patients treated in phase I at the same dose level.  
The ORR endpoint is defined as the incidence of either a complete response or 
a partial response (PR) by the Lugano response criteria as determined by the 
study investigators. All patients that do not meet the criteria for an objective 
response by the analysis cutoff date will be considered non-responders. 
For the ORR endpoint, the Clopper-Pearson 85% and 95% confidence intervals 
(CIs) will be calculated. Confidence intervals adjusting for the 2-stage nature of 
the design may also be provided. Duration of response (DoR) will be calculated 
among responders (CR and PR). The Kaplan-Meier method will be used to 
estimate median DoR and the confidence intervals. Patients who continue to 
respond at the time of the analysis will be censored at the last assessment of 
response.  
Progression-free survival (PFS) is measured from the date of first GDA-201 
dose until the date when progressive disease (PD) is first observed per the 
Lugano response criteria as determined by the study investigators, or death from 
any cause, whichever is earlier. Patients without PD or death will be censored at 
the last available tumor assessment. PFS will be summarized using the Kaplan-
Meier method. 
Overall survival (OS) is measured from the date of first GDA-201 dose until 
death. Patients who are alive will be censored at the last known alive date. OS 
will be summarized using the Kaplan-Meier method. 
Sensitivity analyses of the ORR and PFS based on the assessments by the IRRC 
will also be provided. 
Role of Study Steering 
Committee (SSC) 
 
The SSC will provide oversight of the study.   Recommendations of the SSC 
will be based on an ongoing assessment on the safety and efficacy of the 
treatment regimen. Based on those assessments the SSC may make any of the 
following recommendations: 
• Dose escalation to the next cohort 
• Add patients to the current cohort 
• Dose modification 
• Determination of the MTD 
• Proceed from Phase I to Phase II of the study 
• Proceed to Stage II in each cohort of the Phase II 
• Stop enrollment for one or both cohorts 
 
Additional roles for the SSC include recommendations for: 
• Modifying or removing LD for all patients or for one cohort 
• Safety monitoring throughout the study 


 
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Page 24 of 108 
 
CLIENT CONFIDENTIAL 
Figure 1: 
Study Design Schema 
 
 
 
 


 
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Page 25 of 108 
 
CLIENT CONFIDENTIAL 
Figure 2: 
Patient Treatment & Follow-up Schema  
 
 
  
 


 
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Page 26 of 108 
 
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Table 1: 
Schedule of Events 
 
 
 
Days Pre/Post GDA-201 Infusion 
 
Screening (within 28 
days prior to study 
treatment on Day -10) 
-10 
-5 
-4 
-3 
0 
2 
4 
7 
±1 
14 
±2 
21 
±2 
28 
±2 
42 
±4 
56 
±4 
70 
±4 
90 
±7 
120 
±14 
180 
±14 
270 
±14 
365 
±14 
Written Informed 
Consent1 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Eligibility Criteria2 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical History  
x21 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Disease Assessment 
x 
 
 
 
 
 
 
 
 
 
 
x 
 
 
 
x 
 
x 
 
x 
Positron emission 
tomography (PET)/CT3 
x4 
 
 
 
 
 
 
 
 
 
 
x 
 
 
 
x  
 
x 
 
x 
Tumor biopsy10 
x24 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical Examination5 
x 
x 
x 
 
 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
AE assessment 
 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Weight 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Height 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vital signs6 
x 
x 
x 
x 
x 
x 9 
x 9 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
ECOG performance status 
x 
x 
x 
 
 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Previous cancer treatment 
history 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Concomitant medications7  
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Hematology (CBC 
differential)  
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Chemistry8 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
x 
x 
x 
x 
x 
x 
x 
B2 microglobulin 
x 
 
 
 
 
 
 
 
 
 
 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Ferritin 
 
x 
 
 
 
x 
 
 
x 
x 
x 
 
 
 
 
 
 
 
 
x 
Allelic level HLA Typing 
(HLA-A, B, C, DRB1) 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
GDA-201 Central 
Laboratory Sampling20 
 
x 
 
 
 
x 
x 
x 
x 
x 
 
x 
 
 
 
x 
 
 
 
 


 
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Page 27 of 108 
 
CLIENT CONFIDENTIAL 
 
 
Days Pre/Post GDA-201 Infusion 
 
Screening (within 28 
days prior to study 
treatment on Day -10) 
-10 
-5 
-4 
-3 
0 
2 
4 
7 
±1 
14 
±2 
21 
±2 
28 
±2 
42 
±4 
56 
±4 
70 
±4 
90 
±7 
120 
±14 
180 
±14 
270 
±14 
365 
±14 
Anti-donor HLA testing11 
x 
 
 
 
 
 
 
 
 
 
 
 
 
x 
 
x 
 
 
 
 
CRP 
 
x 
 
 
 
x 
 
 
x 
x 
x 
 
 
 
 
 
 
 
 
 
Serum or urine beta HCG 
(females) 12 
x 
x23 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
GvHD Assessment 
x13 
 
 
 
 
 
 
 
x 
x 
x 
x 
 
 
 
x 
 
x 
 
x 
Electrocardiogram (ECG) 
x 
 
 
 
 
x17 
x17 
x17 
 
 
 
 
 
 
 
 
 
 
 
 
Echocardiogram (ECHO) 
x14 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Bone marrow biopsy or 
aspirate (if previously 
positive) 
x15 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
x15 
 
 
 
 
Lymphodepletion (LD)16 
Cyclophosphamide 
Fludarabine 
 
 
x 
x 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
GDA-20118  
 
 
 
 
 
x 
x22 
 
 
 
 
 
 
 
 
 
 
 
 
 
Rituximab 
 
x 
 
 
x 
 
 
 
 
x19 
 
 
 
 
 
 
 
 
 
 
IL-2 
 
 
 
 
 
x 
x 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 Signed consent is required prior to performing any protocol specific tests, procedures or treatments that are not part of the standard site practice. The ICF signature can be 
obtained earlier than 28 days prior to study treatment 
2 All eligibility criteria must be met before LD commences 
3 If the PET-CT is not of high resolution for accurate disease assessment, the scan must be repeated within 7 days 
4 Baseline PET CT of the neck, chest, abdomen and pelvis: PET-CT performed following the patient’s last line of therapy and prior to signing the consent may be used for 
confirmation of eligibility. If PET CT is performed > 28 days prior to the initiation of study treatments or if patient receives any anti-cancer therapy between screening and LD 
chemotherapy, the PET-CT scan must be repeated to establish a new baseline. PET CT should be performed as close to enrollment as possible 
5 Lumbar puncture and cerebrospinal fluid (CSF) examination only for patients with new or suspicious neurological findings suggestive of CNS involvement, as deemed clinically 
appropriate by the investigator. 
6 Vital signs including blood pressure, heart rate, oxygen saturation, and temperature 
7 Including any cancer treatments, if applicable  
8 Blood chemistry must include (at a minimum): serum creatinine, TBili, alkaline phosphatase, AST, ALT, LDH and magnesium 
9 Including respiratory rate assessment on Days 0 and 2 


 
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CLIENT CONFIDENTIAL 
10 Tumor biopsy is mandatory within 4 months prior to study treatment. A biopsy performed more than 4 months prior to study treatment can be approved at the sponsor’s 
discretion. Tumor biopsy is not mandatory if it is prohibitive from a patient safety perspective, per investigator discretion. 
11  Anti-donor HLA testing for phase I patients only 
12 β-HCG pregnancy test (serum or urine) on all women of child-bearing potential 
13 For patients after any allogeneic cell therapy or HSCT 
14 An ECHO performed following the patient’s last chemotherapy treatment or cellular therapy and within 28 days prior to signing the consent may be used for confirmation of 
eligibility 
15 As clinically indicated 
16 Before LD commences, the criteria in Section 6.2.4 (LD) must be met. If these criteria are not met, then conditioning LD must be delayed until these events are resolved 
17 ECG should be obtained prior to IL-2 administration 
18 Before GDA-201 infusion commences, the criteria in Section 6.2.2 (Investigational product treatment) must be met. If these criteria are not met, then GDA-201 infusion must be 
delayed until these events are resolved 
19 Rituximab may be administered +/- 2 days 
20 Blood draws for GDA-201 central laboratory assays 
 needs to be taken at the beginning of the study 
visit, before the administration of any medications, study drugs, etc.  
21  Any event after written informed consent has been obtained and prior to study treatment initiation should be recorded as medical history unless the event is directly related to a 
screening procedure, in such case it would be considered an AE/SAE and documented on the AE/SAE eCRF. 
22 The second infusion day may not be required based on dose and subject’s weight. 
23 Serum or Urine beta HCG to be done and results should be obtained before rituximab is given to the patient. 
24 Optional for patients who consent for this assessment: 
, see 
section 7.1.7.


 
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2. 
INTRODUCTION  
2.1. 
Overview 
2.1.1. 
Non-Hodgkin Lymphoma 
Non-Hodgkin Lymphomas (NHL) are a heterogeneous group of lymphoproliferative disorders 
originating in B-lymphocytes. T-lymphocytes or natural killer (NK) cells (NK/T-cell 
lymphomas are very rare). In 2022 an estimated 80,470 people were diagnosed with NHL in 
the US and there were approximately 20,250 deaths due to the disease. NHL is the seventh 
leading cause of new cancers cases among men and women, accounting for 4.2% of new cancer 
cases and 3.3% of cancer-related deaths (Siegel et al. 2022). In prospectively collected data 
from the National Cancer Database, diffuse large B-cell lymphoma (DLBCL; 32%), chronic 
lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL; 19%), follicular lymphoma 
(FL; 17%), marginal zone lymphoma (MZL;8%), mantle cell lymphoma (MCL; 4%) and 
peripheral T-cell lymphoma not otherwise specified (PTCL-NOS; 2%) were the major subtypes 
of NHL diagnosed in the United States between 1998 and 2011(Al-Hamadani et al. 2015)(Al-
Hamadani et al. 2015). 
The incidence of NHL increased dramatically between 1970 and 1995 and has moderated since 
the mid1990s. Much of this increase has been attributed to the human immunodeficiency virus 
(HIV) epidemic and the development of acquired immunodeficiency virus (AIDS) related 
NHL.  However, much of the increase in incidence has been observed in patients in their sixth 
and seventh decades and has paralleled a major decrease in mortality from other causes. The 
median age of individuals with NHL has risen in the last two decades(Groves et al. 
2000)(Groves et al. 2000).   
Patients with NHL commonly receive chemoimmunotherapy as initial treatment, and radiation 
therapy may be added if patients have early-stage disease. Most patients respond well to 
treatment, but relapses are frequent and additional therapies including stem cell transplant are 
often needed.  
2.1.1.1. 
Treatment of Diffuse Large B-cell Lymphoma / High Grade-cell Non-
Hodgkin Lymphoma (DLBCL/HGBCL) 
The standard approach for patients with advanced-stage DLBCL/HGBCL is treatment with 
rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) 
chemotherapy . This approach is supported by randomized controlled trials in patients both 
older and younger than 60 years. The addition of rituximab to CHOP chemotherapy improved 
both event-free and overall survival compared with CHOP chemotherapy alone (Feugier et al. 
2005; Habermann et al. 2006). For patients who do not respond to first-line therapy, high-dose 
chemotherapy followed by autologous stem cell transplantation (ASCT) represents a second 
option for cure(NationalComprehensiveCancerNetwork. 2020; Tilly et al. 2015). However, for 
patients who either relapse after or are not eligible for SCT due to refractory disease or frailty, 
treatment outcomes are poor (Crump et al. 2017). Furthermore, even if some patients are 
eligible for transplant, very few actually benefit from this treatment (Crump et al. 2017). 
Response rates to subsequent therapies range from 10–35% in most cases (Crump et al. 2017; 
Coleman et al. 2008; Wiernik et al. 2008; Wang et al. 2019). In an international, multicohort 


 
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CLIENT CONFIDENTIAL 
retrospective non-Hodgkin lymphoma (NHL) research study that retrospectively evaluated 
outcomes in patients with refractory DLBCL (SCHOLAR-1)(Crump et al. 2017), it was found 
that for patients with refractory DLBCL, the objective response rate was 26% (CR rate, 7%) to 
the next line of therapy, and the median overall survival was 6.3 months. Taken as a whole 
these outcomes confirm the need for novel treatments for relapsed/refractory DLBCL. 
More recently, axicabtagene ciloleucil, tisagenleucel and lisocabtagene maraleuce anti-CD19 
CAR-T cell therapies have been approved by Food and Drug Administration (FDA) for the 
treatment of adult patients with relapsed refractory DLBCL, high-grade B-cell lymphoma 
(HGBL) and transformed FL. In 3 multicenter trials CAR-T treatment of aggressive B-cell 
lymphomas resulted in an overall response rate (ORR) of 59%-84% and CR rates of 43%- 61%. 
(Neelapu et al. 2017; Schuster S 2017; Abramson J 2017)(Neelapu et al. 2017; Schuster S 2017; 
Abramson J 2017)Despite these encouraging results the toxicities related to CAR-T cell 
therapy remain a significant problem. There are two main categories of toxicity: cytokine 
release syndrome (CRS) and neurotoxicity, which can be accompanied by organ damage (renal 
failure, cardiac dysfunction, liver dysfunction, etc.). The vast majority of CAR-T cell related 
toxicities resolve within a few weeks, but these potential complications can be life threatening 
and, in certain circumstances, lead to death(Brudno and Kochenderfer 2016; Neelapu et al. 
2018; Lee et al. 2014)(Brudno and Kochenderfer 2016; Neelapu et al. 2018; Lee et al. 2014).  
2.1.1.2. 
Treatment of Follicular (FL) Non-Hodgkin Lymphoma 
The anti-CD20 antibody rituximab has changed the management of FL, and there has been an 
overall improvement in the survival of patients with FL since the incorporation of rituximab 
into treatment of this disease (Fisher et al. 2005). Rituximab as a single agent has been 
compared with watchful waiting in patients with low disease burden and has been found to be 
associated with improved progression-free survival as well as improved quality of life 
(Ardeshna et al. 2014). Overall, asymptomatic patients are commonly observed, while patients 
with a low burden of disease or modest symptoms are treated with rituximab, often with a 
maintenance strategy after initial dosing has been completed. 
Allogeneic stem cell transplant is sometimes considered for patients with FL as part of frontline 
treatment. Although this approach may potentially lead to a cure for a subset of patients, the 
significant treatment-related mortality associated with this approach commonly results in this 
modality being utilized in patients with relapse. 
Approximately 20% of patients with FL progress within the first 24 months after first‐line 
therapy with R-CHOP. Relapse within 24 months is predictive for shorter OS. However, many 
of these cases have primary refractory disease or transformed histology. For example, the 
PRIMA study found among patients with histopathologically confirmed relapse 20% with 
histologic transformation.  
Not all relapses need to be automatically, immediately treated unless there is evidence of a high 
tumor burden(Brice et al. 1997; Ardeshna et al. 2003). Widely used regimens are single‐agent 
rituximab, R-CHOP, RCVP (Rituximab, Cyclophosphamide, Vincristine and Prednisolone), 
RFM (Rituximab, Fludarabine, and Mitoxantrone), or BR (Bendamustine and Rituximab) 
depending on the 1st‐line therapy and duration of response after initial treatment. Patients with 
relapse occurring after 24 months of last treatment have favorable outcome and can be re‐
challenged with the initial protocol. Radiation is also an option in selected patients with 
localized relapse. 


 
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Obinutuzumab plus bendamustine has recently been approved as another option for rituximab‐
refractory patients. The phase III GADOLIN study randomized 396 patients to either six cycles 
of obinutuzumab with bendamustine followed by obinutuzumab maintenance for 2 years or 
bendamustine alone. The median event‐free survival was significantly better with 
obinutuzumab (26.8 vs 13.2 months) (Sehn et al. 2016). With extended follow‐up, recently 
updated results of the study showed significant improvement of OS (median OS not reached 
vs 53.9 months; HR 0.67) in favor of obinutuzumab(Cheson et al. 2018)(Cheson et al. 2018). 
CAR-T therapy has been investigated in indolent lymphomas as well. A study with 14 
relapsed/refractory patients with FL demonstrated CR in 10/14 (71%). Of note, 89% of 
responding patients had maintained the response after median follow‐up time of 2.5 
years(Schuster et al. 2017). More recently Novartis reported a positive Phase 2 in August 2020 
of Kymriah in R/R FL. Yescarta (Gilead) was approved for FL in March 2021. 
2.1.1.3. 
Salvage Therapies for DLBCL/HGBCL and FL  
Taken as a whole, while there are a number of therapeutic options available for patients with 
FL and DLBCL/HGBCL the prognosis of patients with relapsed/refractory NHL who are not 
eligible for high dose chemotherapy and autologous stem cell transplantation (ASCT) is poor, 
and relapse after ASCT portends an even worse prognosis(Tonn et al. 2013; Childs and Berg 
2013)(Tonn et al. 2013; Childs and Berg 2013). The addition of rituximab to standard salvage 
regimens such as ICE (Ifosfamide, Carboplatin and Etoposide) or DHAP (Dexamethasone, 
High dose Cytarabine and Cisplatin) significantly increases responses; however, the responses 
are lower in patients who have already received rituximab as a part of their initial regimen. 
Conventional salvage regimens generally result in substantial morbidity, especially in patients 
over the age of 60 years and the goals of those treatments is usually palliative. There is therefore 
a need for alternative therapies that can provide durable responses without the attendant 
toxicities of current approved regimens. 
2.2. 
Gamida Cell Nicotinamide (NAM) Technology 
2.2.1. 
Background to NK Cells  
NK cells, deﬁned by the cell surface marker phenotype CD3-/CD56+, play a critical role in 
immunosurveillance and immune activation against abnormal cells. Unlike T cell activation, 
NK cells do not require the prior sensitization to a specific tumor antigen for the recognition 
and killing of malignant cells. Upon activation, NK cells have the ability to induce tumor 
apoptosis and are also essential in modulating adaptive immune responses through production 
of chemokines and cytokines such as interferon gamma (IFN-γ) and tumor necrosis factor alpha 
(TNF-α). Due to their innate ability to eliminate tumor cells, infusion of NK cells represents 
an attractive approach to immunotherapeutic treatment of patients with cancers. Moreover, 
specialized tumor specific antibodies can bind with high affinity specific targets on tumor and 
NK cells simultaneously, bringing them in close proximity, and facilitate triggering of the 
killing cascade. Therefore, NK cell therapies can also provide a platform for antibody-
dependent cellular cytotoxicity (ADCC), for broad applicability and efficient treatment of 
refractory tumors. 
Despite preliminary evidence of NK cell activity demonstrated in some patients with leukemia, 
clinical results with previous NK therapies have been disappointing. The insufficient numbers 
of NK cells among peripheral blood mononuclear cells (PBMCs) and the limited ability of 


 
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adoptively transferred NK cells to proliferate in vivo, as well as to home to, and be retained in 
the tumor microenvironment, likely plays a role in their limited efficacy to date. Proliferation 
of NK cells in culture using human serum and stimulating cytokines (IL-2, IL-15, IL-21) has 
been well documented in the scientific literature. However, most reports show a modest 
increase in number of cells and demonstrate a need for additional stimuli for 
proliferation(Childs and Carlsten 2015). 
An important challenge, therefore, in advancing the clinical application of NK cells is to deliver 
an appropriate dose of cells that will display increased homing, retention and proliferation 
activities upon in vivo infusion, while maintaining their cytotoxic capacity.killing 
activity(Childs and Carlsten 2015). 
2.2.2. 
Nicotinamide (NAM) based technology 
NAM is a nicotinamide adenine dinucleotide (NAD) precursor, inhibitor of NAD-consuming 
enzymes, which can balance NAD catabolism. As such, NAM is a master regulator of NAD-
related signaling pathways, NAD-dependent metabolic pathways, histone acetylation and 
ribosylation. It also modulates energetic response pathways, energy homeostasis, resistance to 
cellular stress and maintenance of mitochondrial membrane potential(Son et al. 2013). NAM 
was also demonstrated to decrease loss of function of CD34+ cells expanded in culture and 
enhance migration and homing activities of ex vivo expanded cells(Peled et al. 2012). It was 
therefore hypothesized, that NK cells expanded in culture with NAM will display enhanced 
functionality. 
In a clinical study, patients undergoing myeloablative allogenic HSCT with cord blood- derived 
CD34+ cells cultured with NAM (omidubicel) demonstrated prompt and durable 
engraftment(Horwitz et al. 2019). 
Early preclinical studies show that NK cell cultures, stimulated with IL-15 and NAM, augment 
tumor cytotoxicity and cytokine (TNF-α and IFN-γ) secretion. Unlike the known changes 
induced in NK cell cultures with cytokines, NK cells expanded with NAM maintained 
expression of activating and inhibitory receptors, 
 
 
 
NAM cultured NK cells demonstrated better retention in the bone marrow, spleen and 
peripheral blood of irradiated NSG mice, as well as increased in vivo proliferation.  
These findings were mechanistically supported by a substantial increase in CD62L (L-selectin) 
expression in cultures treated with NAM. CD62L is pivotal for NK cell trafficking to the BM 
and lymph nodes (LN) and their homeostatic proliferation (Juelke et al. 2010). CD62L receptor 
expression is known to be down regulated following expansion in culture, thus hindering the 
ability of NK cells to be recruited into the tumor microenvironment and tumor bearing LN. The 
up-regulation of CD62L on NK cells may result in high affinity binding to endothelial cells 
expressing CD62L binding proteins, which would improve NK cell homing from the 
circulation into the BM and secondary lymphoid tissues. This could enhance the ability of 
adoptively transferred NK cells to mediate anti-tumor effects against hematological 
malignancies such as multiple myeloma (MM), leukemia and lymphoma. 
 
 
 




 
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rituximab 375 mg/m2 IV, with appropriate premedications and monitoring per the respective 
package inserts.  
GDA-201 was administered on Day 0 and Day +2. Patients were premedicated with 
acetaminophen 
mg PO and/or diphenhydramine
 mg PO before and 4 hours after the 
infusion. corticosteroids were to be avoided fromDay -3 through Day +14.  
Interleukin-2 (IL-2) 
 was administered subcutaneously (SC) on Day 0, Day +2, 
and Day +4. 
GDA-201 doses in the phase I dose-finding portion of study MT2015-46 are outlined in Table 
2. Enrollment began at dose level 1 with cohorts of 2 patients without regards to NHL or MM 
diagnosis. An increase in dose level was not to occur until at least one patient assigned to a 
dose level completed the Day 28 follow-up. 
 
Table 2:  
GDA-201 Dose Cohorts in Study MT2015-46 
Dose Cohort 
TNCa dose 
Dose 1 
Day 0 
TNC dose 
Dose 2 
Day +2 
TNC dose 
Dose 1+2 
1 
1 x 107/kg 
1 x 107/kg 
2 x 107/kg 
2 
5 x 107/kg 
5 x 107/kg 
10 x 107/kg 
3 
1 x 108/kg 
1 x 108/kg 
2 x 108/kg 
a TNC: total nucleated cells 
 
The expansion phase of Study MT2015-46 was to enroll 10 patients with each diagnosis (MM 
or NHL) treated at the MTD identified in the phase I dose-finding portion of the study.  
The study was amended in February 2019 to allow retreatment with GDA-201 of patients with 
stable disease (SD) or response. The treatment regimen is similar to that of initial treatment 
including use of disease specific mAb, timing of the GDA-201 cell infusions, and IL-2, however 
LD is not to be re-administered if retreatment with GDA-201 takes place within 100 days of 
the first dose, and may be eliminated or reduced to two days if retreatment takes place after 
Day +100.  
2.2.3.3. 
Study Results MT2015-46 
Study MT2015-46 was open to enrollment October 18, 2017 and enrollment completed on  
August 15, 2022.  35 patients were treated with GDA-201. Seventeen patients have received 
the maximum target dose 
 
 
 
 
 
No DLTs were observed in patients treated at any of the three dose cohorts tested.. The most 
common CTCAE v 5.0 Grade 3 and 4 AEs were neutropenia and thrombocytopenia, febrile 
neutropenia, leukopenia and hypertension. All events were transient. There were no neurotoxic 
events, confirmed cytokine release syndrome (CRS), graft vs host disease (GvHD) or marrow 
aplasia. One patient died within 30 days of enrollment from RSV resulting in complicated 
pneumonia and E-coli sepsis with renal failure. 
Of the 35 patients treated, 16 had MM and 19 had NHL (10 follicular, 2 transformed, 6 diffuse 
large cell lymphoma, 1 mantle cell lymphoma).  


 
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Among 19 NHL patients evaluable for response an ORR of 74% and a CR rate of 68% were 
recorded. All responding patients exhibited a clinical response within 28 days post-GDA-201 
infusion. Four NHL patients received a second dose of GDA-201 without additional 
lymphodepleting chemotherapy. Two patients (one with FL and one with DLBCL) showed a 
further deepening of response from PR to CR. The median duration of response was 16 months 
(range 5-36 months). Progression-free survival (PFS) at 1 and 2 years were estimated at 50% 
(95% CI = 27-69%) and 35% (95% CI = 14-58%), respectively. Two patients underwent HSCT 
and one had autologous HSCT for consolidation. After censoring for the transplant, the PFS at 
2 years was 19% (95%CI 2-51%) and overall survival (OS) at 2 years was 73% (CI = 43-89%). 
Clinical efficacy data in patients are illustrated in the Swimmer’s Plot below (Figure 3), in 
which the duration of response is plotted for individual patients.  
 
Figure 3: 
Responses of NHL Patients in Study MT2015-46 
 
Persistence of GDA-201 in patients treated with fresh GDA-201 in Study MT2015-was 
explored using flow cytometry detecting donor-HLA-specific CD56+ CD3- cells in peripheral 
blood. Preliminary results from 15 patients (Figure 4) demonstrated the persistence of donor 
GDA-201 in peripheral blood up to day 7-10 (day 7 range 2-55% donor cells), as well as 
enhanced in vivo proliferation (median Ki67 99%).  
Figure 4: 
Percentage of Donor-HLA-positive NK cells in peripheral blood in Study 
MT2015-46 (n=15) 
 


 
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2.3. 
Overall Risk Benefit 
The use of NK cells may offer a promising tool for immunotherapy in patients with various 
relapsed and/or refractory hematologic malignancies. The infusion of allogeneic NK cells 
could elicit a potent anti-tumor activity via natural cytotoxicity, cytokine stimulated 
cytotoxicity, and ADCC, when infused in combination with a tumor-targeting antibody. Based 
on the available nonclinical data with cryopreserved GDA-201, and the preliminary clinical 
results of the GDA-201 in its fresh formulation, the ex vivo expansion of NK cells in the 
presence of NAM can enable the clinical application of GDA-201 cells that will display 
antitumor activity. 
This study aims to assess the safety and efficacy of GDA-201 infusion in patients with relapsed 
and/or refractory B Cell NHL, in conjunction with rituximab. In addition to the potential 
functional and quantitative advantages of GDA-201, the study aims to evaluate the use of cells 
derived from unrelated donors, with no requirement for HLA matching with the patient. This 
approach could broaden the access of patients to a potentially effective treatment for a severe 
life-threatening disease by providing an off-the-shelf therapy. 
The risk-benefit relationship has been carefully considered in the preparation of the study 
protocol. Patients entered onto this trial have failed prior therapies and have limited therapeutic 
options for the treatment of their lymphoma. The study shall be discontinued in the event new 
findings indicate a relevant increase in risk or deterioration of the risk-benefit relationship. 
2.4. 
Rationale for Study Design & Dosages 
2.4.1. 
Study Population 
GDA-201 is intended for the treatment of hematological cancers expressing CD20 on the cell 
surface. This includes aggressive, fast growing lymphomas, such as high grade B cell 
lymphoma and DLBCL and indolent, slow growing lymphomas like follicular lymphoma (FL). 
It is not currently planned to include other B cell cancers in which only a small percentage of 
the tumor cells express the antigen on their cell surface (Hodgkin’s Lymphoma, Acute 
Lymphoblastic Leukemia (ALL), multiple myeloma), high grade lymphomas (e.g. Burkitt’s 
Lymphoma), or Chronic Lymphocytic Leukemia (CLL) with extensive peripheral disease. 


 
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Eligible patients have relapsed or refractory lymphoma following at least 2 prior lines of 
therapy (at least one of which contained chemotherapy and at least one of which contained an 
anti-CD20 monoclonal antibody (mAb)).  
Patients who failed prior CAR-T cell therapy or are considered ineligible for CAR-T therapy 
per the Investigator's discretion are eligible. As such, the Investigator may determine that 
patients are eligible for the study if they are not considered to be candidates for CAR-T therapy 
due to their primary disease status, comorbidities or other considerations. 
2.4.2. 
Dosage GDA-201 
This is a phase I/II study which seeks to determine the safety and efficacy of cryopreserved, 
allogeneic GDA-201 with rituximab, when given with LD and followed by a short course of 
low-dose IL-2, in patients with relapsed/refractory B Cell NHL.  
In a previous phase 1 study, (Bachanova 2020) doses between 
 
 
 
 cells/kg given 
over two separate infusion days were associated with 74% ORR and DLT was not observed. It 
is expected that safety and efficacy will be observed in this study at the same dosage levels. 
However, several modifications have been introduced to GDA-201 production in order to 
enable immediate treatment access to patients and create an off-the-shelf therapy. 
 
 
 
 The sourcing of cells for GDA-201 has also been 
modified from haploidentical related donors to unrelated allogeneic donors. Therefore it will 
be important to confirm safety as part of current study. 
As such, dose escalation will start with a GDA-201 dose of 2.5 x 107 cells/kg, and will be 
escalated to a maximal dose of 2 x 108 cells/kg, consistent with the doses assessed in the 
previous study. Patients in each dose level will be dosed according to the closest available 
GDA-201 bag size, allowing for deviations up to 33% from the intended dose. 
2.4.3. 
Host Conditioning 
The Adoptive Cell Therapy (ACT) process can be subdivided into 3 steps: host conditioning, 
cell transfer, and post-transfer cell support. The host conditioning step can include multiple 
components – LD, IL-2 administration and in NHL, rituximab administration. Despite the 
widespread use of conditioning regimens, it is unclear if all of the components are necessary 
and how they should be administered. In the previous University of Minnesota trial (MT2015-
46) all of these components were employed prior to administration of GDA-201 cells. The 
resulting high response rate observed was notable. However, utilization of host conditioning 
regimens is associated with significant toxicity and the need for hospitalization. Equally as 
significant there has never been a randomized clinical trial (RCT) evaluating the contribution 
of LD and host conditioning to ACT.  While it is desirable to modify and or delete some of 
these conditioning components, it is also possible they are necessary to achieve similar 
response rates in the current study. The hope is that some or all of those components are not 
necessary. Therefore, a host conditioning regimen is included as part of the current study but 
may be modified or deleted following review by the SSC. The rationale for each of the Host 
Conditioning components is summarized below. 


 
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2.4.3.1. 
Lymphodepleting (LD) Chemotherapy  
Lymphodepleting chemotherapy is used with other cellular therapy regimens in order to 
prolong persistence of cells and increase efficacy. Studies in mice and humans have suggested 
that the effectiveness of ACT therapy can be improved by lymphodepleting the host prior to 
cell infusion(Dudley et al. 2002; Dudley et al. 2008). Several mechanisms have been proposed 
for this beneficial effect. Previous studies shown that LD removes endogenous lymphocytes 
functioning as cellular sinks for homeostatic cytokines and allows free cytokines to induce 
survival and proliferation of adoptively transferred cells(Gattinoni et al. 2005). Utilization of 
LD has been incorporated into approved CAR-T therapies and have primarily employed 
chemotherapy with cyclophosphamide and fludarabine(Neelapu et al. 2017; Schuster et al. 
2019)(Neelapu et al. 2017; Schuster et al. 2019).  
Whether LD will be necessary as part of allogenic NK cell therapy is unknown. LD has been 
incorporated into the majority of clinical trials exploring the use of NK cells in hematologic 
malignancies(Liu et al. 2021). It was noted in one study that LD resulted in endogenous 
cytokine release and that elevated levels of IL-15 were associated with improved clinical 
response(Bachanova et al. 2018).(Bachanova et al. 2018) 
2.4.3.2. 
IL-2 Administration 
 It has been shown that freshly isolated, resting NK cells are generally less lytic as compared 
to NK cells primed via various strategies(Bryceson et al. 2006). Although NK cells do not 
require immunologic priming, certain conditions have been shown to lower their threshold of 
activation and enhance antitumor immunity. Cytokines such as IL2 and IL15 provide not only 
a proliferative signal to NK cells, but also enhance function(Woan and Miller 2019).  
Clinical protocols of ACT infusing ex vivo expanded tumor-infiltrating lymphocytes (TIL) or 
T-cell receptor (TCR) engineered peripheral blood T cells have employed the concomitant 
administration of IL-2. It is usually administered intravenously at the highest tolerated dose 
every 8 h in an inpatient hospital setting to support expansion and function of the adoptively 
transferred cells(Rosenberg et al. 2008). This dosing regimen results in a high peak of exposure 
along with associated acute toxicities of a short duration that is designed to activate the IL-2 
receptor(Charych et al. 2017). There have been attempts at decreasing the toxicity and 
improving the pharmacokinetics (PK) of IL-2 by lowering the doses and administering 
subcutaneously (SC), but it is unclear if the benefit is maintained compared to high dose IL-
2(Chapuis et al. 2012). Given the higher activity of GDA-201 cells it is possible a lower and 
less toxic dose of IL-2 will be sufficient.  
2.4.3.3. 
Rituximab Administration 
NK cells are a well described mediator of rituximab induced tumor lysis(Mentlik James, 
Cohen, and Campbell 2013). NK cells have the capacity to mediate ADCC upon recognition 
of the Fc segment of IgG bound to cell surfaces. This antigen-specific NK cell targeting 
mechanism appears to play an important role in tumor eradication by several therapeutic tumor 
specific monoclonal antibodies (mAb), such as trastuzumab, rituximab, and elotuzumab. In 
patients with NHL, the addition of rituximab enhances NK cell mediated ADCC against CD20-
positive NHL cells.  
Administration of rituximab several days prior to administration of GDA-201 has the added 
potential of depleting circulating B-lymphocytes which permits greater targeting of the 


 
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lymphoma cells. Previous studies of rituximab have documented a dose-dependent, rapid, and 
specific B cell depletion (Maloney et al. 1994). 


 
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3. 
STUDY OBJECTIVES, HYPOTHESIS & STUDY ENDPOINTS 
3.1. 
Objectives  
3.1.1. 
Study Hypothesis 
The overall study objective is to evaluate the safety and efficacy of cryopreserved, allogeneic 
GDA-201, when given with lymphodepleting chemotherapy and followed by a short course of 
low-dose IL-2, in patients with relapsed/refractory B Cell NHL 
3.1.2. 
Study Objectives 
 
Phase I objectives: 
• Assess the safety of GDA-201 + rituximab as determined by dose limiting toxicities 
• Determine the maximum tolerated dose (MTD), to be applied as the recommended 
Phase II dose (RP2D) 
 
Phase II objectives: 
• Assess the safety and efficacy of GDA-201 in separate cohorts of patients with FL and 
DLBCL/HGBCL  
3.2. 
Study Endpoints  
3.2.1. 
Primary Endpoints  
o Primary endpoint- Phase I: 
o DLT and safety of GDA-201 
o Primary endpoint: Phase II: 
o Overall response rate (ORR) 
3.2.2. 
Secondary Endpoints  
o Secondary endpoints: phase I: 
o ORR  
o Secondary endpoints: Phase II: 
o ORR Independent Radiological Review Committee (IRRC) 
o Duration of response (DOR). (Investigator Assessment) 
o Progression free survival (PFS). (Investigator Assessment) 
o Overall survival (OS) (Investigator Assessment) 
o Safety and tolerability (Investigator Assessment) 
3.2.3. 
Exploratory Endpoints  
o 
 
 
 
 


 
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4. 
STUDY POPULATION 
4.1. 
Number of Patients  
• A maximum of 99 patients will be treated as follows: 
o 12-36 patients in the Phase I portion 
o 63 patients (32 in FL cohort and 31 in DLBCL/HGBCL cohort) in the Phase II 
portion     
4.2. 
Eligibility Criteria   
4.2.1. 
Inclusion Criteria   
1. Patients must have relapsed/refractory FL or DLBCL/HGBCL that has failed 
conventional therapy defined as follows (for the Phase I dose escalation: patients with 
marginal zone lymphoma or mantle cell lymphoma are also eligible): 
a. Lymphoma characterized by current and/or historical expression of CD20 as 
determined by flow cytometry or immunohistochemistry. 
b. Received at least 2 prior lines of therapy (at least one of which contained 
chemotherapy and at least one of which contained an anti-CD20 monoclonal 
antibody (mAb)).  
c. Transplant ineligible patients allowed assuming they meet criterion b.  
d. Failed prior CAR-T cell therapy or are considered ineligible per the 
Investigator's discretion.  
e. FL transformed to DLBCL/HGBCL: Must have received at least 1 line of 
therapy after transformation to DLBCL/HGBCL 
2. Patients must have measurable disease as defined by the Lugano response criteria 
(Cheson et al. 2014) as determined by study investigators. Lesions that have been 
previously irradiated will be considered measurable only if progression has been 
documented following completion of radiation therapy 
3. Patients must be at least 18 years of age. In Dose level 1 patients must be at least 75 kg.   
4. Patients must have ECOG performance status 0 or 1  
5. Patients must have adequate hematologic, hepatic, renal, cardiac and pulmonary 
function prior to any study treatment defined as: 
a. Absolute neutrophil count (ANC) ≥ 1000/μL 
b. Platelet count ≥ 50,000/μL  
c. Creatinine ≤ 1.5 mg/dL or creatinine clearance ≥50 mL/min  
d. Serum ALT or AST ≤ 3 x upper limit of normal (ULN) 
e. Total bilirubin (TBili) ≤ 1.5 x ULN unless patient with a history of Gilbert’s 
syndrome 
f. Cardiac ejection fraction ≥ 45%, no evidence of pericardial effusion as 
determined by an echocardiography 
g. Baseline oxygen saturation > 92% on room air 


 
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h. No clinically significant pleural effusion 
If organ dysfunction is due to lymphoma involvement and not due to prior toxicities the 
following laboratory parameters are permitted: 
a. Platelet count ≥ 30,000 if due to hypersplenism or disease involvement in 
marrow  
b. Total bilirubin (TBili) ≤ 3 x ULN if due to hepatic disease involvement  
c. Growth factors are permitted to meet required ANC if cytopenia is due to 
marrow disease involvement 
6. No Class II or greater New York Heart Association Functional Classification criteria 
(Appendix A) or serious cardiac arrhythmias likely to increase the risk of cardiac 
complications of cytokine therapy (e.g. ventricular tachycardia, frequent ventricular 
ectopy, or supraventricular tachyarrhythmia requiring chronic therapy)  
7. Patients must be able to be off systemic corticosteroids (with the exception of 
physiological steroid replacement therapy) and other immunosuppressive drugs for at 
least  5 half-lives prior to GDA-201 infusion and up until day 14 post GDA-201 infusion 
(excluding preparative regimen pre-medications), unless approved by the sponsor. 
8. Patients after allogeneic HSCT are eligible if they are at least 6 months after the 
transplant andoff all immunosuppressive drugs. 
9. Patients after allogeneic HSCT or any other allogeneic cell therapy are eligible if there 
is no active Graft-versus-Host Disease (GvHD) 
10. No evidence of ongoing neurotoxicity or cytokine release syndrome from prior 
therapies 
11. Sexually active females of childbearing potential and males with partners of 
childbearing potential must agree to use effective contraception from the time of 
screening pregnancy test and for at least 4 months after completion of therapy 
12. Patient signs the written informed consent after being aware of the nature of the 
patient’s disease and willingly consents to the treatment program after being informed 
of alternative treatments, potential risks, benefits, and discomforts 
4.2.2. 
Exclusion Criteria   
1. Pregnancy, as indicated by a positive serum or urine human chorionic gonadotrophin 
(HCG) test, or lactation 
2. Active bacterial, fungal, or viral infection that is uncontrolled or requiring systemic 
antimicrobials for management. Simple urinary tract infection (UTI) and 
uncomplicated bacterial pharyngitis are permitted if responding to active treatment 
3. HIV infection not controlled on therapy, and/or with active viremia (HIV viral load 
needs to be undetectable ), or AIDS defining illnesses. 
4. History of acute or chronic active hepatitis B or C infection not documented to be 
cleared per current Infectious Diseases Society of America (IDSA) guidelines (see 
Appendix B). Patients at risk for reactivation of HBV infection must be on prophylactic 
anti-HBV antiviral therapy 
5. Patients with active autoimmune disease requiring immunosuppressive therapy. 
Patients with a history of autoimmune-related hypothyroidism on a stable dose of 


 
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thyroid replacement hormone and patients with controlled type 1 diabetes mellitus 
(DM) on a stable insulin regimen may be eligible for this study 
6. History of severe asthma and currently treated with chronic asthma medications (a 
history of mild asthma requiring inhaled steroids only is eligible) 
7. Live vaccine <6 weeks prior to start of therapy 
8. Patient with detectable CSF malignant cells, or brain metastases, or with a history of 
central nervous system (CNS) lymphoma or primary CNS lymphoma, CSF malignant 
cells or brain metastases. Patients with a history of CNS involvement can be included 
if cleared by magnetic resonance imaging (MRI) and CSF for at least 6 months 
9. History of malignancy other than nonmelanoma skin cancer or carcinoma in situ (e.g. 
cervix, bladder, breast, prostate) unless disease free for at least 2 years 
10. Presence of any indwelling line or drain (e.g., percutaneous nephrostomy tube, 
indwelling foley catheter, biliary drain, or pleural/peritoneal/pericardial catheter). 
Dedicated central venous access catheters such as a Port-a-Cath or Hickman catheter 
are permitted 
11. History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis 
obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active 
pneumonitis per chest imaging at screening. History of radiation pneumonitis in the 
radiation field (fibrosis) is allowed 
12. Known hypersensitivity to any of the study treatments, gentamycin, albumin, DMSO 
or any other GDA-201 excipient 
Note: Infusion reactions with rituximab are common. Patients with a history of infusion 
reactions to rituximab that can be managed with recommended pre-medications should 
not be excluded 
13. Time between previous treatment and first dose of study treatment (rituximab):  
a. Allogeneic HSCT < 6 months prior to study treatment 
b. ASCT < 3 months prior to study treatment 
c. CAR-T < 2 months prior to study treatment 
d. Major surgery or chemotherapy < 4 weeks prior to study treatment (6 weeks for 
melphalan) 
e. Radiation therapy < 2 week prior to study treatment 
f. Monoclonal antibodies including checkpoint blockade < 2 weeks prior to study 
treatment (does not apply to rituximab) 
g. Antibody-Drug Conjugates (ADCs) including polatuzumab vedotin and 
loncastuximab tesirine < 4 weeks prior to study treatment, unless approved by 
the sponsor 
h. Targeted therapies, Bispecific T cell Engagers (BiTEs),  small molecule 
inhibitors or any investigational therapy within 5 half-lives of the drug, unless 
approved by the sponsor 
  


 
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5. 
PATIENT ENROLLMENT & DOSE LEVEL ASSIGNMENT  
5.1. 
Written Consent 
Written consent must be obtained prior to the performance of any research related tests or 
procedures. 
5.2. 
GDA-201 Cell Dose Level Assignment   
 
Up to 4 dose levels of GDA-201 cells will be tested in this study followed by the expansion 
cohort. Assignment of the dose level will be provided by the sponsor or designee. This is 
an open label study with no blinding or randomization. In Phase I, patients will be assigned 
to the currently enrolling GDA-201 dose level without regards to underlying disease. In 
Phase II patients will be non-randomly assigned to either the FL or DLBCL/HGBCL cohort 
based on their underlying disease. 
5.2.1. 
Patients Who Do Not Begin Study Treatment 
 
 
If a patient signs consent  and is later found not able to begin the first dose of study treatment, 
for whatever reason, the patient will be removed from study. The patient will be considered 
a screen/baseline failure and the reason for removal from study will be clearly indicated. 
Patients will be allowed to re-screen. The patient will be replaced to fulfill study enrollment 
requirements. 
 
5.3. 
Patient Enrollment 
  
Once all screening assessments are completed and the patient’s eligibility is confirmed, 
study treatment can begin. Patient enrollment is defined as receiving the first dose of 
rituximab (Day -10). 


 
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6. 
STUDY TREATMENT 
This is an open-label, non-randomized, interventional, single group assignment study of GDA-
201, an allogeneic cryopreserved NK cell therapy derived from donor peripheral blood, in 
combination with rituximab, monoclonal anti-CD20 antibody, for patients with relapsed or 
refractory B Cell non-Hodgkin lymphoma (NHL). 
The study is divided into a phase I dose escalation and a phase II expansion study.  
 
Patients with relapsed or refractory FL or DLBCL/HGBCL will receive GDA-201 followed by 
a short course of low-dose interleukin-2 (IL-2) (for the Phase I dose escalation: patients with 
marginal zone lymphoma or mantle cell lymphoma are also eligible). Rituximab will be 
administered prior to and after GDA-201 infusion (see Figure 1 for the study schema).   
6.1. 
Treatment Plan 
6.1.1. 
Phase I: Dose Escalation 
 
The objective of Phase I is to evaluate the safety of GDA-201 for patients with FL,  
DLBCL/HGBCL, marginal zone lymphoma or mantle cell lymphoma. The MTD will be 
determined based on DLTs. 
 
As outlined in Table 3 , the starting dose will be 2.5 x 107 cells/kg. 
Safety within each cohort will be assessed by the incidence of DLTs (see Section 11.2 for DLT 
definitions) over an observation period of 28 days. For the first 3 patients enrolled at each dose 
level, a 28-day staggering interval of DLT free observation period is required to be completed 
before treating a subsequent patient in the same dose level cohort. Dose escalation to the next 
dose level can only proceed after the third patient has completed a 28-day DLT free observation 
period and following discussion with the SSC. 
 
Table 3: 
Dosing Cohorts 
 
Dose Level 
Dose* 
1 
2.5x107 cells/kg 
 2 
5x107 cells/kg 
 3 
1x108 cells/kg 
4 
2x108 cells/kg 
*Based on GDA-201 dosing table allowing for a maximal 33% deviation from the intended dose 
(Table 5). 
 
Based on the safety and tolerability of GDA-201 in the first 3 evaluable patients after the first 
cycle of treatment, escalation to a subsequent dose level or addition of patients to a current 
dose level will occur based upon the following criteria: 


 
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• If there are no GDA-201-related DLTs experienced within 28 days, dose escalation 
to the subsequent dose level may proceed 
• If 1 of 3 patients at a dose level experiences a DLT within 28 days following a single 
dose of GDA-201, 3 additional patients may be enrolled into the study at the current 
dose level 
• If there are no further DLTs experienced in the 3 additional patients within 28 days 
following a single dose, escalation to the next dose level may proceed 
• If a DLT occurs in ≥ 2 patients in any dose group of 3 to 6 patients within 28 days 
following a single dose, dose escalation will stop   
Additional patients will be treated at the preceding lower dose level, if needed, to have at least 
6 patients treated at that dose level. If 6 patients were previously treated, the preceding lower 
dose level will provisionally be considered the MTD pending any decision to enroll additional 
patients (up to 12 patients enrolled in backfilled cohorts) at the discretion of the study sponsor 
to further characterize the DLT and safety profile by histology (follicular lymphoma or 
DLBCL/HGBCL) prior to phase II expansion. 
Patients within each cohort will be assessed for DLTs, and enrollment in each cohort will 
continue to occur sequentially until a MTD is reached. The MTD will be applied as the 
recommended Phase II dose (RP2D). 
 
Dose escalation will stop at completion of Dose Level 4 even if the MTD is not identified. At 
the discretion of the study sponsor, after the dose escalation phase across the four doses is 
complete, up to an additional 12 patients enrolled in backfilled cohorts may be treated to further 
characterize the DLT and safety profiles by histology (follicular lymphoma or 
DLBCL/HGBCL) at one or two dose levels prior to the phase II expansion. This will be 
designated as “backfilling” a cohort in order to ensure that the cohort enrolls a minimum of 3 
patients per histology. With the addition of these backfill patients, the MTD and/or RP2D may 
be determined. The RP2D may be different by histology (follicular lymphoma or 
DLBCL/HGBCL).  
6.1.2. 
Phase II: Expansion Phase 
 
The objective of the Phase II expansion cohort is to evaluate the safety and efficacy of GDA-
201 in two patient cohorts, FL and DLBCL/HGBCL. 
 
Patients will be treated with GDA-201 at the RP2D along with LD. 
 
The patients will be followed for treatment response by positron emission tomography (PET)-
CT at 28 days following the first GDA-201 infusion, and continue to be followed at 90, 180 
and 365 days following the initial treatment. All patients will be followed for one year from 
the first GDA-201 infusion to determine time to relapse and progression free survival. 
 
Patients with either FL or DLBCL/HGBCL will continue to be included in separate cohorts by 
diagnosis. Each disease group will accrue independently, closing to enrollment once a total of 
63 (32 in FL cohort and 31 in DLBCL/HGBCL cohort) evaluable patients are enrolled. 
 


 
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In order to provide optimal patient care and to account for individual medical conditions, 
investigator discretion may be used in the prescribing of all supportive care drug therapy (i.e. 
acetaminophen, diphenhydramine, antimicrobials, etc.).  
6.2. 
Treatment Regimen 
The following table summarizes the overall treatment regimen that will be employed: 
 
Table 4: 
Study Treatment Plan 
Component  
Dose 
Days 
Rituximab 
 
 
-10, -3, +14* 
Lymphodepletion 
(LD)** 
 
  
 
  
-5, -4, -3 
GDA-201 
 
0, +2 
Interleukin-2 
  
0, +2, +4. 
    * The last rituximab dose be administered +/- 2 days  
** LD chemotherapy dose adjustments will be permitted according to local institutional guidelines and with 
sponsor approval. 
 
Administration of GDA-201 and other study treatments should follow the schedule outlined in 
this section . 
6.2.1. 
Rituximab 
o Will be administered with appropriate pre-medications and monitoring per the 
package insert  
o A ±2-day window is permissible for the last rituximab dose (Day 14) 
o NOTE:  
▪ Biosimilars may be used 
▪ SC administration is NOT permitted 
6.2.2. 
Investigational Product GDA-201 
Before GDA-201 infusion commences, the following criteria must be met. If these criteria are 
not met, then GDA-201 infusion must be delayed until these events resolve. 
• No evidence or suspicion of infection. Patient must not be receiving systemic anti-
microbials for the treatment of an active infection within 48 hours prior to GDA-201 
infusion (prophylactic use of anti-microbials is allowed) 
• No clinically evident changes in bone marrow, renal, hepatic, pulmonary or cardiac 
function since screening 
• Creatinine clearance is at or above limits set in eligibility criteria 
• No acute neurological toxicity > grade 1 (with the exception of peripheral neuropathy) 


 
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• In addition, if any of the following are known to occur, the GDA-201 infusion may 
need to be delayed. Contact the Study Medical Monitor before GDA-201 infusion 
commences for guidance: 
o CRP is ≥100 mg/L 
o Temperature is ≥ 38.0°C within 48 hours prior to GDA-201 infusion. 
Unexplained fever requires pan-culture, respiratory viral panel, chest CT scan 
and any additional symptom-directed workup to rule out occult infection 
o WBC count of ≥ 20,000/μL within 48 hours prior to GDA-201 infusion 
o If the GDA-201 infusion is delayed > 2 weeks, lymphodepleting chemotherapy 
may need to be repeated. In all cases of GDA-201 infusion delays, contact the 
Study Medical Monitor for guidance 
• Each GDA-201 treatment will be given over two infusion days: Day 0 and Day +2. 
Depending on the patient’s weight, GDA-201 may be given only on Day 0. For the 
Phase I, both infusion days and 24 hours subsequent follow up will be performed during 
an inpatient stay 
• The 2nd GDA-201 infusion day will be performed if all toxicities from 1st  infusion day 
decrease to ≤ CTCAE grade 2 
• GDA-201 is provided in cryobags. See Table 5 for the GDA-201 dosing table per 
patient weight – note that patients may require one or more GDA-201 bags per infusion 
day to complete their treatment according to the assigned dose level 
• On each day of GDA-201 infusion: 
o Pre-medications: Patients should be pre-medicated with 
acetaminophen/paracetamol 
 mg PO and/or diphenhydramine 
 mg 
PO before starting GDA-201 infusions and 4 hours ±30 minutes after completing 
the GDA-201 infusions (note that this dose will also provide the pre-medication 
for IL-2 dosing) 
o See Sections 8.4 and 8.5 (Handling and Preparation of GDA-201; and 
Administration) and the product handling manual for GDA-201 preparation and 
infusion instructions. 
o The infusion rate of GDA-201 should not exceed 
 
o Infuse GDA-201 within 2 hours from dilution to end of infusion 
o A minimal interval of 1 hour is required from the start of infusion of the first 
bag, to the start of infusion of the subsequent bag, to ensure the minimal infusion 
time according to the endotoxin limit
 
 
• The GDA-201 cells are intended to be infused by gravity without additional support 
(examples of additional support are the use of a volumetric pump or  a syringe push).  
• GDA-201 should be given with blood infusion set with filter 
 
• Hydration will be administered per institutional guidelines. Any elevation of daily 
metabolic monitoring will be treated with more aggressive hydration, while being 
attentive to fluid overload 
Follow-up after GDA-201 Infusion  


 
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Patients on the Phase I will be hospitalized to receive treatment with GDA-201 followed by a 
24 hour post infusion observation period. Patients should not be discharged from the hospital 
until all GDA-201-related non-hematological toxicities return to ≤ Grade 1. Patients may be 
discharged with non-critical and clinically stable or improving toxicities (e.g., renal 
insufficiency) even if > Grade 1, if deemed appropriate by the investigator. Patients should 
remain hospitalized for ongoing GDA-201 -related fever, hypotension, hypoxia, or if deemed 
necessary by the treating investigator. 
Table 5: 
GDA-201 Dosing Table 
 
 
Number of GDA-201 Bags to be Infused1 
 
 
Day 0 
Day 2 
Dose Level2 
Patient Weight (kg) 
 
 
 
 
 
 
Dose Level  1:  
2.5 x 107 cells/kg 
Up to 75 
Not Applicable5 
75 and above 
1 
 
 
 
Dose Level 2:  
5 x 107 cells/kg 
Up to 75 
1 
 
 
 
75 and above 
1 
 
1 
 
Dose Level 3:  
1 x 108 cells/kg 
Up to 60 
1 
 
1 
 
60 to < 90 
 
1 
1 
 
90 and above 
 
1 
 
1 
Dose Level 4:  
2 x 108 cells/kg 
Up to 60 
 
1 
 
1 
60 to < 90 
 
2 
 
1 
90 and above 
 
2 
 
2 
1. 
Depending on the patient’s weight, GDA-201 may be given only on Day 0. 
2. 
Dose level is assigned according to the actual infused dose. Deviations up to 33% from the intended dose 
level are acceptable to accommodate the closest GDA-201 bag size. 
3. 
 
 
 
 
 
5. 
No dosing is feasible due to maximal allowed deviation from intended dose of 33% 
6.2.3. 
Interleukin-2 
 
o IL-2 will be given subcutaneously (SC) at 
 
o For patients weighing < 45 kilograms, the IL-2 will be given at 
  
o Pre-medication with acetaminophen/paracetamol 
 mg PO and 
diphenhydramine 
mg PO/IV before the IL-2 dose and 4 hours after each dose 


 
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of IL-2 is recommended (note that this dose can also provide the post-medication 
for GDA-201 dosing) 
o On days of GDA-201 cell infusion, IL-2 will be administered no sooner than 4 hours 
after GDA-201 administration has been completed 
o For the Phase I, the first two doses will be administered as part of the hospitalization 
for the GDA-201 cell infusion. The 3rd IL-2 dose may be given as an outpatient 
o If the patient has experienced grade 2 or greater GDA-201 infusion related toxicity 
on Day 0 or Day +2, the dose of IL-2 may be held for up to 48 hours. If the toxicity 
resolves to grade 1 or better within 48 hours, IL-2 may be given with all planned 
doses to be given; however the administration of remaining dose(s) must be at least 
24 hours apart 
o If IL-2 cannot be started within 48 hours after the Day 0 GDA-201 infusion, no IL-
2 will be given and the patient will be replaced, but remain evaluable for primary 
and secondary endpoints 
o Instructions for dilution and administration of IL-2 can be found in Appendix G. 
6.2.4. 
Lymphodepleting (LD) Chemotherapy  
Before LD commences, the following criteria must be met. If these criteria are not met, then 
lymphodepleting chemotherapy must be delayed until these events resolve. 
• No evidence or suspicion of infection 
• No clinically evident changes in bone marrow, renal, hepatic, pulmonary or cardiac 
function since screening 
• Creatinine clearance is at or above limits set in eligibility criteria  
• No acute neurological toxicity > Grade 1 (with the exception of peripheral neuropathy) 
• In addition, if any of the following are known to occur, a delay in lymphodepleting 
chemotherapy may be required. Contact the Study Medical Monitor before 
lymphodepleting chemotherapy commences for guidance 
o WBC count of ≥ 20,000/μL within 48 hours prior to lymphodepleting chemotherapy 
o CRP is ≥100 mg/L 
o Temperature is ≥ 38.0° C within 48 hours prior to lymphodepleting chemotherapy. 
Unexplained fever requires pan-culture, respiratory viral panel, chest CT and any 
additional symptom- directed workup to rule out occult infection 
o If any other screening assessments or procedures are repeated between enrollment 
and the start of lymphodepleting chemotherapy and results are outside the eligibility 
criteria 
The 3 day lymphodepleting regimen of fludarabine and cyclophosphamide will be 
administered in accordance with the below daily dosing instructions. 
o Fludarabine 
 mg/m2 is administered as a 0.5 to 1-hour intravenous (IV) infusion 
once a day for 3 doses beginning on Day -5 
o Cyclophosphamide 
 mg/m2 is administered as a 1 to 2-hour IV infusion once a 
day for 3 doses on Day -5 
o IV hydration with 700-1000 mL of 0.9% NaCl given prior to cyclophosphamide on 
the days of infusion. An additional 700-1000 mL of 0.9% NaCl at the completion 
of the cyclophosphamide infusion guidelines 


 
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o Dosing is based on body surface area calculation (BSA) unless actual body weight 
(ABW) is > 150% above ideal body weight (IBW), in which case the dose should 
be computed using adjusted body weight. LD chemotherapy dose adjustments will 
be permitted according to local institutional guidelines and with sponsor approval. 
o Patients should be instructed to drink plenty of liquids during and for 24 hours 
following the chemotherapy (approximately 2 liters/24 hours). In general patients 
should be kept well-hydrated but closely monitored to prevent fluid overload 
o Mesna is a detoxifying agent used to inhibit hemorrhagic cystitis induced by 
chemotherapy. The active ingredient mesna is a synthetic sulfhydryl compound 
designated as sodium-2-mercaptoethane sulfonate with a molecular formula of 
C2H5NaO3S2 
▪ Mesna should be administered per institutional guidelines. Refer to the 
most recent version of the package insert for specific details surrounding 
the administration of mesna 
o Patients are to receive allopurinol 300 mg PO daily, unless known allergy, 
continuing until Day +7 or as clinically indicated 
o Patients  are to receive antimicrobial prophylaxis: 
▪  Anti-viral therapy with acyclovir 400 mg PO twice daily.  
▪ Anti-PCP prophylaxis is recommended - Sulfamethoxazole-Trimethoprim 
x 2/week until Day 60 
▪ Antibiotic and antifungal prophylaxis is recommended: levofloxacin 
250mg/day begin Day 0 (give only if ANC < 1000); fluconazole 100mg/day 
begin Day 0 (continue until ANC > 1000) 
6.2.5. 
Concomitant Therapy for Symptom Management 
Medications may be administered for the management of symptoms associated with the 
administration of GDA-201, IL-2 and Rituximab as needed. These might include analgesics, 
anti-emetics, anti-histamines, diuretics, anti-anxiety medications, and medications for pain 
management, including narcotic agents. 
NOTE: Systemic corticosteroids: Given the profound deleterious effects of systemic 
corticosteroids on NK function, they are to be avoided from 5 half-lives prior to GDA-201 
infusion through Day +14. It is advised to refrain from systemic corticosteroids use up to Day 
90 unless clinically indicated. Physiological steroid replacement therapy is permitted.  
6.2.6. 
Concomitant Medications  
During screening and throughout the study, patients may take only stable doses of medications 
for chronic conditions that are not specifically excluded by the protocol. The Medical Monitor 
should be consulted by the Investigator if there are any concerns about what constitutes a stable 
dose or what is a chronic condition. 
 


 
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7. 
STUDY VISITS AND PROCEDURES 
7.1. 
Study Procedures 
7.1.1. 
Informed Consent 
Before a patient’s participation in the clinical study, the investigator is responsible for obtaining 
written informed consent from the patient after adequate explanation of the study design, 
anticipated benefits and the potential risks. Patients should sign the most current IRB/IEC 
approved ICF prior to any study specific activity or procedure is performed. 
The consent process and the patient’s agreement or refusal to participate in the study is to be 
documented in the patient’s medical records. If the patient agrees to participate, the ICF is to 
be signed and personally dated by the patient and by the person who conducted the informed 
consent discussion. The original signed ICF will be retained in accordance with institution 
policy and IRB/IEC requirements with a copy of the ICF provided to the patient. 
All patients who are enrolled into the study should be re-consented with any updated version 
of the IRB/IEC approved ICF if relevant to their participation in the study. 
7.1.2. 
Demographic Data  
Demographic data will be collected as per country and local regulations and guidelines. Where 
applicable, demographic data will include sex, year of birth, race, ethnicity, and country of 
enrollment to study their possible association with patient safety and treatment effectiveness. 
7.1.3. 
Medical and Previous Cancer Treatment History 
Relevant medical history prior to the start of AE reporting will be collected. Relevant medical 
history is defined as data on the patient’s concurrent medical condition that would be typically 
shared in a referral letter. All findings will be recorded in the CRFs. 
In addition to the medical history, all history related to the patient’s disease, treatment and 
response to treatment will be collected and must date back to the original diagnosis. 
For patients who are being referred from another clinic or institution to the participating 
research center, copies from the patients chart should be obtained. 
7.1.4. 
Physical Exam, Vital Signs and ECOG Performance Status 
Physical exams will be performed during screening and at times noted in the Schedule of Event 
(SOE). Changes noted in subsequent exams when compared to the baseline exam will be 
reported as an AE. 
During GDA-201 administration/hospitalization, vital signs including blood pressure, heart 
rate, respiratory rate, oxygen saturation, and temperature will be monitored before, during and 


 
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after each GDA-201 infusion and then routinely according to standard of care. If the patient 
has a fever (temperature >38.2oC), vital signs will be monitored more frequently as clinically 
indicated. 
Performance status as measured by the ECOG scale will be performed to quantify the patient’s 
general well-being and ability to perform activities of daily life. 
7.1.5. 
Cardiac Function  
Each patient’s cardiac function, as measured by Left Ventricular Ejection Fraction (LVEF), 
will be assessed during the screening period to confirm study eligibility. No evidence of 
clinically significant pericardial effusion as required by eligibility will also be confirmed. Both 
LVEF and pericardial effusion will be assessed prior to study enrollment by ECHO (MUGA 
also acceptable). An ECHO performed following the patient’s last chemotherapy treatment and 
within 28 days prior to signing the consent may be used for confirmation of eligibility. 
A 12-lead ECG will also be performed during the screening period. 
7.1.6. 
Disease Response Assessment  
Patients will be evaluated for disease response by the site investigator at times indicated in the 
SOE. Disease assessments will be evaluated per the Lugano response criteria ) Flow 
cytometric, molecular or cytogenetic studies will not be used to determine response. 
Baseline PET-CT scans of the neck, chest, abdomen and pelvis, along with the appropriate 
imaging of all other sites of disease are required. Patients will have their first post GDA-201 
infusion planned PET-CT tumor assessment 28 days following the GDA-201 infusion and at 
regular intervals as highlighted in the SOE during the post treatment follow-up. 
Post GDA-201 administration disease assessments will be used to determine the time when 
progressive disease (PD) occurs. Patients 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 SOE. 
A bone marrow aspirate and/or biopsy should be performed only when the patient had bone 
marrow involvement with lymphoma prior to therapy or if new abnormalities in the peripheral 
blood counts or blood smear cause clinical suspicion of bone marrow involvement with 
lymphoma after treatment. The bone marrow aspirate and/or 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. 


 
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7.1.7. 
Laboratory 
The below samples will be collected at the time points indicated in the SOE. Additional 
samples (e.g., blood, urine, CSF, tissue, etc) may be collected as needed for further safety 
testing.  
Local laboratory analysis: 
• Tumor biopsy  
• Optional for patients who consent for this assessment: 
 
 
 
 
 
• Complete Blood Count with Differential  
• Chemistry panel must include (at the minimum): serum creatinine, total bilirubin 
(TBili), alkaline phosphatase, AST, ALT, LDH and magnesium. 
• C-reactive protein (CRP) 
• Ferritin 
• B2 microglobulin 
• Allelic level HLA typing  
• Anti-donor HLA-testing  
• Serum or urine beta HCG  for females of childbearing potential. If the screening 
pregnancy test is positive, the patients should not be enrolled. If a standard of care 
pregnancy test is collected during the course of the study, and the result is positive, the 
investigator should contact the Study Medical Monitor for instructions. If a female 
partner of a male patient becomes pregnant during the conduct of the study, it must be 
reported by contacting the Study Medical Monitor for instructions 
Central laboratory analysis: 
• Blood draws for GDA-201 central laboratory assays 
 
 for will be collected according to the SOE and 
shipped to a central laboratory for processing. The blood draw needs to be taken at the 
beginning of the study visit, before the administration of any medications, study drugs, 
etc. 
• 
 
 
7.2. 
Study Visits 
7.2.1. 
Study Duration 
The total duration of participation for each patient is approximately 13 months. The main study 
will be considered complete when the last patient enrolled has completed the last protocol 


 
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required follow-up visit. Patients who enroll in the long-term follow up sub-study will be 
followed for an additional 5 years, up to 6 years following the initial GDA-201 infusion.  
The patients will be followed for treatment response by PET-CT at 28 days following the first 
GDA-201 infusion, and continue to be followed at 90, 180and 365 days following the initial 
GDA-201 treatment. All patients will be followed for one year from the first GDA-201 infusion 
to determine time to relapse and progression free survival. 
Should the patient fail to return to the clinic for a scheduled protocol specific visit, sites will 
need to make 2 attempts by a combination of telephone and mail (if applicable) to contact the 
patient. Sites must document both attempts to contact the patient. If a patient does not respond 
within 1 month after the second contact the patient will be considered lost to follow-up and no 
additional contact will be required. 
At any time during the study period, if a patient fails to achieve SD, PR or CR, or progresses 
following a response, or begins another cellular therapy treatment for his/her disease, the 
patient’s post treatment assessment will be recorded and he/she will be followed for SAEs 
through 30 days following the last dose of study treatment and then for survival through one 
year after the first GDA-201 infusion. 
7.2.2. 
Screening 
The screening period begins from the date the patient signs the IRB/IEC approved informed 
consent form (ICF) and continues through commencement of study treatments. Informed 
consent must be obtained before performing  any non-standard of care study specific 
procedures. Procedures that are part of standard of care are not considered study specific 
procedures and may be performed prior to obtaining consent and used to confirm eligibility. 
Confirmation of this data must occur within the time allowance as outlined below and in the 
SOE. 
After written informed consent has been obtained, patients will be screened to confirm study 
eligibility and participation. Only patients who meet the eligibility criteria listed in Section 4.2 
and who commence study treatments will be enrolled in the study. If at any time prior to 
enrollment the patient fails to meet the eligibility criteria, the patient should be designated as a 
screen failure on the patient screening log with the reasons for failing screening. 
Investigative sites will maintain a log of all screened patients who were reviewed and evaluated 
for study participation. Information collected on the screening log should include limited 
information such as the date of screening, date the patient was enrolled or the reason for why 
the patient failed screening. 
The following assessments/procedures are to be completed during the screening period at the 
time points outlined in the SOE. 
• Written Informed Consent 
• Eligibility Criteria – All eligibility criteria must be met before LD commences 


 
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• Medical history  
• Disease assessment - baseline disease assessment must be performed after completion 
of prior chemotherapy 
• GvHD assessment (for patients after allogeneic HSCT or any other allogeneic cell 
therapy). See Appendix C 
• Concomitant medications documentation and previous cancer treatment history 
• Physical examination including height and weight 
o Patients with symptoms of CNS malignancy such as new onset severe 
headaches, neck stiffness, seizures, encephalopathy, cranial nerve deficits, or 
any focal neurologic findings on physical exam will have lumbar puncture for 
examination of CSF 
• Vital signs including blood pressure, heart rate, oxygen saturation, and temperature 
• ECOG performance status 
• ECG 
• ECHO for LVEF and pericardial effusion assessment 
o An ECHO performed following the patients last chemotherapy treatment and 
within 28 days prior to signing the consent may be used for confirmation of 
eligibility 
• PET-CT 
o Baseline PET CT of the neck, chest, abdomen and pelvis 
▪ PET-CT performed following the patients last line of therapy and prior 
to signing the consent may be used for confirmation of eligibility 
▪ If PET CT is performed > 28 days prior to the initiation of study 
treatments or if patient receives any anti-cancer therapy between 
screening and LD chemotherapy, the PET-CT scan must be repeated to 
establish a new baseline. PET CT should be performed as close to 
enrollment as possible 
• Laboratories 
o Tumor biopsy is mandatory within 4 months prior to study treatment, unless it 
is prohibitive from a patient safety perspective, per investigator discretion or 
unless approved by the sponsor.   
o Optional for patients who consent for this assessment:
 
 
 
 
 
 
o Chemistry panel 
o CBC with differential 
o B2 microglobulin 
o β-HCG pregnancy test (serum or urine) on all women of child-bearing potential 
o Allelic level HLA Typing (intermediate resolution HLA-A, B, C, DRB1) 
 
o Anti donor HLA Testing 
o Bone marrow biopsy or aspirate (if previously positive) as clinically indicated. 
o Lumbar puncture only for patients with new or suspicious neurological findings 
suggestive of CNS involvement 


 
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• Serious Adverse Event (SAE)/ Adverse Event (AE) reporting since the time of consent 
and prior to study treatment initiation only if the event is directly related to screening 
procedure (refer to section 15.2 for Procedures for Adverse Events (AEs) Recording 
and Reporting) 
Re-Screening 
Patients who are unable to complete the screening assessments or do not meet the eligibility 
criteria during the 28-day screening period will be permitted to rescreen one time.  If 
rescreening occurs within 28 days of the initial signing of the informed consent, only the 
procedure(s)/assessment(s) that did not originally meet the eligibility criteria need to be 
repeated. All other initial screening procedures/assessments do not need to be repeated. If 
rescreening occurs more than 28 days from the signing of the initial informed consent, patients 
must be reconsented (if  > 3 months has elapsed) and repeat all expired screening 
procedures/assessments. 
7.2.3. 
Study Visit Day -10 
• Physical examination including weight 
• AE assessment 
• Vital signs including blood pressure, heart rate, oxygen saturation, and temperature 
• ECOG performance status 
• Laboratories 
o Chemistry panel 
o CBC with differential 
o Ferritin 
o CRP 
o GDA-201 central laboratory sampling (before rituximab administration) 
o Serum or urine β-HCG pregnancy test (results should be obtained before 
rituximab is administered). 
• Concomitant medications documentation  
• Administration of rituximab with appropriate pre-medications and monitoring (refer to 
Section 6.2.1) 
• Serious Adverse Event (SAE) reporting (refer to Section 15.2 for Procedures for 
Adverse Events (AEs) Recording and Reporting) 
7.2.4. 
Study Visit Day -5, Day -4 and Day -3 
Before Lymphodepleting Chemotherapy commences, the criteria in Section 6.2.4 must be met. 
If these criteria are not met, then LD must be delayed until these events resolve. 
• Weight 
• AE assessment  
• Vital signs including blood pressure, heart rate, oxygen saturation, and temperature 
• ECOG performance status 
• Laboratories 
o Chemistry panel 


 
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o CBC with differential 
• Concomitant medications documentation 
• Administration of Lymphodepleting Regimen, consisting of fludarabine and 
cyclophosphamide for three consecutive days (refer to Section 6.2.4)  
• Serious Adverse Event (SAE) reporting (refer to Section 15.2 for Procedures for 
Adverse Events (AEs) Recording and Reporting) 
On Day -5 also add the following: 
• Physical Examination 
 
On Day -3 also add the following:  
• Administration of rituximab with appropriate pre-medications and monitoring (refer to 
Section 6.2.1) 
7.2.5. 
Study Visit Day 0 
Before GDA-201 infusion commences, the criteria in Section 6.2.2 (Investigational Product 
Treatment) must be met. If these criteria are not met, then GDA-201 infusion must be delayed 
until these events resolve. 
• Physical examination including weight 
• AE assessment  
• Vital signs including blood pressure, heart rate, respiratory rate, oxygen saturation, and 
temperature 
• ECOG performance status 
• ECG should be obtained before IL-2 administration 
• Laboratories 
o Chemistry panel 
o CBC with differential 
o Ferritin 
o CRP (C-reactive protein) 
o GDA-201 central laboratory sampling (before GDA-201 administration)  
• Concomitant medications documentation  
• Administration of study drug GDA-201 cell infusion, pre-medications and hydration 
(refer to Section 6.2.2)  
• Administration of Interleukin-2 (IL-2) with appropriate pre-medications (refer to 
Section 6.2.3) 
• Serious Adverse Event (SAE) reporting (refer to Section 15.2 for Procedures for 
Adverse Events (AEs) Recording and Reporting) 
7.2.6. 
Study Visit Day 2 
Before GDA-201 infusion commences, the criteria in Section 6.2.2 (Investigational Product 
Treatment) must be met. If these criteria are not met, then GDA-201 infusion must be delayed 
until these events resolve. 
• Physical examination including weight 
• AE assessment  


 
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• Vital signs including blood pressure, heart rate, respiratory rate, oxygen saturation, and 
temperature 
• ECOG performance status 
• ECG should be obtained before IL-2 administration 
• Laboratories 
o Chemistry panel 
o CBC with differential 
o GDA-201 central laboratory sampling (before GDA-201 administration if 
infused on that day) 
• Concomitant medications documentation  
• Administration of study drug GDA-201 cell infusion, pre-medications and hydration 
(refer to Section 6.2.2)  
• Administration of Interleukin-2 (IL-2) with appropriate pre-medications (refer to 
Section 6.2.3)   
• Serious Adverse Event (SAE) reporting (refer to Section 15.2 for Procedures for 
Adverse Events (AEs) Recording and Reporting) 
7.2.7. 
Study Visit Day 4  
• Physical examination including weight 
• AE assessment  
• Vital signs including blood pressure, heart rate, oxygen saturation, and temperature 
• ECOG performance status 
• ECG should be obtained before IL-2 administration 
• Laboratories 
o Chemistry panel 
o CBC with differential 
o GDA-201 central laboratory sampling 
• Concomitant medications documentation  
• Administration of Interleukin-2 (IL-2) with appropriate pre-medications (refer to 
Section 6.2.3).  
• Serious Adverse Event (SAE) reporting (refer to Section 15.2 for Procedures for 
Adverse Events (AEs) Recording and Reporting) 
7.2.8. 
Study Visit Day 7 
• Physical examination including weight 
• AE assessment 
• Vital signs including blood pressure, heart rate, oxygen saturation, and temperature 
• ECOG performance status 
• Laboratories 
o Chemistry panel  
o CBC with differential 
o CRP (C-reactive protein) 
o Ferritin 
o GDA-201 central laboratory sampling 
• GvHD Assessment  


 
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• 
Concomitant medications documentation 
• 
Serious Adverse Event (SAE) reporting (refer to Section 15.2 for Procedures for 
Adverse Events (AEs) Recording and Reporting) 
7.2.9. 
Study Visit Day 14 
• Physical examination including and weight 
• AE assessment 
• Vital signs including blood pressure, heart rate, oxygen saturation, and temperature 
• ECOG performance status 
• Laboratories 
o Chemistry panel 
o CBC with differential 
o GDA-201 central laboratory sampling 
o Ferritin 
o CRP 
• GvHD assessment 
• Concomitant medications documentation  
• Administration of rituximab with appropriate pre-medications and monitoring (refer to 
Section 6.2.1) 
• Serious Adverse Event (SAE) reporting (refer to Section 15.2 for Procedures for 
Adverse Events (AEs) Recording and Reporting) 
7.2.10. 
Study Visit Day 21 
• Physical examination including and weight 
• AE assessment 
• Vital signs including blood pressure, heart rate, oxygen saturation, and temperature 
• ECOG performance status 
• Laboratories 
o Chemistry panel 
o CBC with differential 
o Ferritin 
o CRP 
• GvHD assessment 
• Concomitant medications documentation  
• Serious Adverse Event (SAE) reporting (refer to Section 15.2 for Procedures for 
Adverse Events (AEs) Recording and Reporting) 
7.2.11. 
Study Visit Day 28 
• Physical examination including and weight 
• AE assessment 
• Vital signs including blood pressure, heart rate, oxygen saturation, and temperature 
• ECOG performance status 
• Laboratories 
o Chemistry panel 
o CBC with differential 
o B2 microglobulin 


 
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o GDA-201 central laboratory sampling 
• GvHD assessment 
• Concomitant medications documentation  
• PET-CT 
• Disease Assessment 
• Serious Adverse Event (SAE) reporting (refer to Section 15.2 for Procedures for 
Adverse Events (AEs) Recording and Reporting) 
7.2.12. 
Study Visit Day 42 
• Physical examination including and weight 
• AE assessment 
• Vital signs including blood pressure, heart rate, oxygen saturation, and temperature 
• ECOG performance status 
• Laboratories 
o Chemistry panel 
o CBC with differential 
o B2 microglobulin 
• Concomitant medications documentation  
• Serious Adverse Event (SAE) reporting (refer to Section 15.2 for Procedures for 
Adverse Events Recording and Reporting) 
7.2.13. 
Study Visit Day 56 
• Physical examination including and weight 
• AE assessment 
• Vital signs including blood pressure, heart rate, oxygen saturation, and temperature 
• ECOG performance status 
• Laboratories 
o Chemistry panel 
o CBC with differential 
o B2 microglobulin 
o Anti-donor HLA testing 
• Concomitant medications documentation  
• Serious Adverse Event (SAE) reporting (refer to Section 15.2 for Procedures for 
Adverse Events (AEs) Recording and Reporting) 
7.2.14. 
Study Visit Day 70 
• Physical examination including and weight 
• AE assessment 
• Vital signs including blood pressure, heart rate, oxygen saturation, and temperature 
• ECOG performance status 
• Laboratories 
o Chemistry panel 
o CBC with differential 
o B2 microglobulin 
• Concomitant medications documentation  


 
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• Serious Adverse Event (SAE) reporting (refer to Section 15.2 for Procedures for 
Adverse Events (AEs) Recording and Reporting) 
7.2.15. 
Study Visit Days 90, 120, 180, 270 and 365  
• Physical examination including and weight 
• AE assessment 
• Vital signs including blood pressure, heart rate, oxygen saturation, and temperature 
• ECOG performance status 
• Laboratories 
o Chemistry panel 
o CBC with differential 
o B2 microglobulin 
o Ferritin – on day 365 only 
o GDA-201 central laboratory sampling – on Day 90 only 
o Anti-donor HLA testing – on Day 90 only 
• Concomitant medications documentation  
• Serious Adverse Event (SAE) reporting (refer to Section 15.2 for Procedures for 
Adverse Events (AEs) Recording and Reporting) 
On visit Days 90, 180 and 365 only, also perform: 
• PET-CT  
• Disease Assessment 
• GvHD assessment 
On visit Day 90 only, also perform: 
Bone marrow biopsy or aspirate (if previously positive) as clinically indicated. 
 
7.2.16. 
Termination Visit 
• Physical examination including and weight 
• AE assessment 
• Vital signs including blood pressure, heart rate, oxygen saturation, and temperature 
• ECOG performance status 
• Laboratories 
o Chemistry panel 
o CBC with differential 
o B2 microglobulin 
o Ferritin  
• Concomitant medications documentation  
• Serious Adverse Event (SAE) reporting (refer to Section 15.2 for Procedures for 
Adverse Events (AEs) Recording and Reporting) 
• PET-CT  
• Disease Assessment 
• GvHD assessment 


 
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7.3. 
Long Term Follow-Up (LTFU) 
Patients enrolled on the study will be offered a separate informed consent for long term follow 
up. Patients will be enrolled in the long term follow-up sub-study after they have completed 
the one year study follow up. For these patients, information on the following will be collected: 
• Subsequent therapies  
• Disease status  
• Survival 
Assessments may be performed as per the standard of care at individual institutions. Data may 
be obtained by review of medical records from the clinical center, through the patient’s primary 
care physician, and/or contact by phone at the time points 2 years, 3 years, 4 years, 5 years and 
6 years following the initial GDA-201 infusion. 


 
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8. 
STUDY MEDICATION: GDA-201 
8.1. 
Description 
GDA-201 is an allogeneic cryopreserved NK cell therapy derived from donor peripheral blood. 
GDA-201 is supplied in 2 doses: 
1. 
 
 
 
 
 
 
 
8.2. 
Manufacturing and Shipping 
GDA-201 is an allogeneic cell therapy comprised of NK cells isolated from peripheral blood 
leukapheresis of individual allogeneic donors. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
8.3. 
GDA-201 Supply 
Labeling and packaging of GDA-201 is performed according to the relevant Manufacturer's 
SOP. Cryopreserved GDA-201 is shipped in a cryoshipper equipped with a calibrated data 
logger. The shipment of GDA-201 will be controlled by the sponsor in order to assure that 
shipment conditions are appropriately maintained and documented, as detailed in the product 
handling manual.  
Upon arrival at clinical site GDA-201 should be kept 
 
  
8.4. 
Handling and Preparation of GDA-201 
Handling and Preparation of GDA-201 are described in the GDA-201 Product Handling 
Manual. 
GDA-201 should not be irradiated under any circumstances. 


 
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Prior to its infusion, GDA-201, its labels, and the related documentation must be identified and 
checked at the clinical center according to the product handling manual. The clinical center 
should confirm that GDA-201 was shipped in appropriate conditions and all cryobags are 
within their shelf life. The related forms must be completed and signed/dated to document this 
review. 
Thawing and dilution of GDA-201 by the clinical site's personnel will be performed 
immediately prior to infusion. Each GDA-201 cryobag should be separately thawed, diluted 
and infused according to the product handling manual. Any subsequent GDA-201 cryobag to 
be infused should not be thawed before confirming the infusion of the preceding GDA-201 bag 
was completed.  
A minimal interval of 1 hour is required from the start of the infusion of the first GDA-
201 bag, to the start of the infusion of the subsequent GDA-201 bag, to ensure the minimal 
infusion time according to the endotoxin limit 
 
). 
In a brief summary of the preparation process for infusion, the GDA-201 cryobag is removed 
from liquid nitrogen storage, checked for integrity, and is placed in a
 water bath. As soon 
as the cells are completely thawed, the bag is removed from the water bath and transferred to 
a safety grade A cabinet.  
 
 
 
 
 
 
8.5. 
Administration 
GDA-201 should be infused via a central venous catheter as per site practice. GDA-201 is 
intended to be given by gravity without additional support (examples of additional support are 
the use of a volumetric pump or  a syringe push).  
GDA-201 should be given with blood infusion set with filter 
 
The infusion rate of GDA-201 should not exceed 
. The entire content of the GDA-
201 bag should be infused as soon as possible after thaw.  
The total duration of each GDA-201 infusion will not exceed 2 hours from dilution to end of 
infusion. 
The process should be repeated for each subsequent GDA-201 bag according to the dosing 
requirement in section 6.2.2.  
GDA-201 contains human blood cells. Follow international and country specific  guidelines 
and local biosafety SOP for handling and disposal to avoid potential transmission of infectious 
diseases. 
 
 


 
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9. 
STUDY STEERING COMMITTEE (SSC) 
The data emerging from this study will be reviewed periodically by the SSC. Based on an 
ongoing assessment on the safety and efficacy of the treatment regimen, the SSC may make 
any of the following recommendations: 
• Dose escalation to the next cohort 
• Add patients to the current cohort 
• Dose modification 
• Determination of the MTD 
• Proceed from Phase I to Phase II of the study 
• Proceed to stage II in each cohort of the Phase II 
• Stop enrollment for one or both cohorts 
 
Additional roles for the SSC include recommendations for: 
• Safety monitoring throughout the study 
• Modifying or removing LD for all patients or for one cohort, as follows 
➢ Reduce the LD drug doses for all patients or one cohort 
➢ Remove use of LD for all patients or one cohort 
➢ Proceed with patient enrollment with and without LD in parallel (1:1 
allocation)  
➢ Stop enrollment for one regimen 
➢ Repeat LD for subsequent GDA-201 treatment cycles 
Changes that increase LD dosing for the planned patient population will not be 
implemented without a protocol amendment. 
  
SSC recommendations will be provided to the sponsor. The SSC will include representatives 
from the Investigators , Medical Monitor and the sponsor.  
In the Phase I dose escalation, AEs, clinical laboratory results, cardiac function results, and 
vital signs will be assessed at least through 28 days following treatment in each cohort in a 
minimum of three patients to assess DLT. Based on the safety and tolerability of GDA-201 in 
the first 3 evaluable patients after the first cycle of treatment, escalation to a subsequent dose 
level or addition of patients to a current dose level will occur. See Section 6.1.1 for details on 
the criteria for dose escalation and MTD determination. 
Throughout the study the SSC will continue to review the study data periodically. If an alert is 
triggered by the study stopping criteria (see Section 12.6), the SSC will consider the data in 
depth and make recommendations to the sponsor. It is understood that SSC recommendations 
to the sponsor are not binding and that the sponsor is the sole party responsible for final 
decisions regarding modification or continuation of the trial. 


 
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10. 
DISCONTINUATION, TERMINATION OR COMPLETION OF 
STUDY  
10.1. 
Study Discontinuation  
Study interventions, including LD and GDA-201 administration, should be discontinued by the 
investigator if the investigator believes that it is in best interest of the subject or if any of the 
following situations occur:  
• Disease progression  
• Death 
• Initiation of another systemic treatment for NHL 
• Investigator’s decision 
• Subject noncompliance / protocol violations 
• Study terminated by sponsor  
• Subject withdrawal  
• Lost to follow-up  
10.2. 
Study Termination  
The study can be terminated by the sponsor, Institutional Review Board (IRB) / Ethics 
Committee or Regulatory Agency at any time.  
10.2.1. 
Subject Withdrawal  
A subject may withdraw from the study at any time at his/her own request or may be withdrawn 
at any time at the discretion of the investigator for safety, behavioral, compliance, or 
administrative reasons. 
If the subject withdraws consent for disclosure of future information, the sponsor may retain 
and continue to use any data collected before such a withdrawal of consent. 
If a subject withdraws from the study, he/she may request destruction of any samples taken and 
not tested, and the investigator must document this in the site study records. 
Sponsor may request subject to be withdrawn. 
10.2.2. 
Lost to follow-up 
A subject will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site.  
The following actions must be taken if a subject fails to return to the clinic for a required study 
visit: 
• The site must attempt to contact the subject and reschedule the missed visit as soon 
as possible and counsel the subject on the importance of maintaining the assigned 


 
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visit schedule and ascertain if the subject wishes to and/or should continue in the 
study 
• Before a subject is deemed lost to follow-up, the sites will need to make 2 attempts 
by a combination of telephone and mail (if applicable) to contact the patient. Sites 
must document both attempts to contact the patient. 
10.2.3. 
If a patient does not respond within 1 month after the second 
contact the patient will be considered lost to follow-up and no 
additional contact will be requiredStudy Completion  
A subject is considered to have completed the main  study if:  
- 
followed according to the protocol to the Day 365 visit, or 
- 
disease progression, or 
- 
death, or  
- 
has received a new treatment for NHL (including stem cell transplant) 
Subjects who have completed the Day 365 visit can be followed for an additional 5 years in an 
optional LTFU sub-study.  
Subjects who have not completed the main study according to the above list will be followed 
for SAEs through 30 days following the last dose of study treatment. These subjects will  
complete a Termination Visit (see section 7.2.16) if possible, and then will be followed for 
survival through one year after the first GDA-201 infusion. Subjects who consented to the 
LTFU will  be followed for further 5 years in an optional LTFU sub-study.  
 
 
10.2.4. 
Termination Visit 


 
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11. 
TERMINATION VISIT WILL INCLUDE ALL RELEVANT 
STUDY ASSESSMENTS (SEE SECTION 7.2.16) NOT 
EVALUATED WITHIN 2 WEEKS PRIOR TO THE SUBJECT 
TERMINATION. SAFETY EVALUATIONS AND CRITERIA 
11.1. 
Safety Evaluation and Dose Escalation 
Safety will be evaluated by the SSC including Investigators and Medical Monitor. In the Phase 
I dose escalation, AEs, clinical laboratory results, cardiac function results, and vital signs will 
be assessed through at least 28 days following the first GDA-201 dose in each cohort in a 
minimum of three patients to assess DLT. Based on the safety and tolerability of GDA-201 in 
the first 3 evaluable patients after the first cycle of treatment, escalation to a subsequent dose 
level or addition of patients to a current dose level will occur. 
11.2. 
Dose-Limiting Toxicity Definition 
 
On discovery, all DLTs should be immediately reported (within 24 hours of knowledge of the 
event) to Parexel. 
DLTs defined as one of the following, within the first 28 days of the first dose of GDA-201, 
by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-
CTCAE) v 5.0 (Appendix F). Acute GvHD will be assessed according to the Consensus 
Conference on Acute GvHD grading ((Przepiorka et al. 1995)Appendix D): 
• Steroid refractory Grade II acute GvHD. Steroid refractory GvHD is defined as 
GvHD that does not respond to at least 1 mg/kg/day or equivalent of prednisone 
within 7 days of initiating therapy 
• Grade III or IV acute GvHD  
• Grade 4 infusion reaction  
• Grade 4 or 5 related adverse event (AE)  
• Grade 3 or above cardiac, central nervous system or pulmonary adverse event. 
• Any Grade 3 or above non-hematologic adverse event that does not resolve to 
Grade 2 or below within 72 hours, with the exception of renal or hepatic adverse 
events which may take up to 7 days to resolve 
• Treatment emergent ≥Grade 3 autoimmune disorder 
• Grade 3 or above allergic reaction that does not recover to Grade II or below 
within 24 hours 
• Grade 4 cytopenia lasting beyond Day 42 (the 28-day DLT observation period 
will be extended to confirm) 
11.3. 
Continuation of Therapy  
Patients will continue to receive the same dose level of GDA-201 as assigned at study entry 
unless dose delay or discontinuation is required to manage toxicities. Intra-patient GDA-201 
dose escalation is not allowed. Patients who experience GDA-201 related DLT may continue 
treatment provided that the toxicity can be controlled and that it resolves to either Grade 1 or 
baseline. 




 
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• immune mediated toxicity may occur with any cell therapy: cytokine release 
syndrome, neurotoxicity, macrophage activation syndrome are very rare but could 
be serious and even fatal 
11.5.1.2. Interleukin-2 (IL-2) 
 
Toxicities associated with IL-2 include: 
• fever, chills 
• skin rash 
• fatigue, tiredness 
• decreased platelets 
• nausea and vomiting 
• fluid retention and weight gain 
• hypothyroidism 
• infection 
• abnormal renal function test 
• abnormal liver function test 
To reduce the intensity of fever and chills, pre-medication with acetaminophen and 
diphenhydramine before and 4 hours after each dose of IL-2 is recommended. Premedication 
specifics and dose modifications for unacceptable IL-2 related toxicities are found in Section 
6.2.3.  
11.5.1.2.1. Hypotension (systolic blood pressure < 90 mm Hg)  
IL-2 should be held for hypotension (defined as systolic blood pressure less than 90 mm Hg) 
if in the presence of any clinically significant symptoms (in the opinion of the treating 
physician), until the systolic blood pressure reading is stable. If mild dehydration is suspected, 
an IV fluid bolus may be used per standard of care. 
11.5.2. 
Management of Expected GDA-201 Toxicities 
11.5.2.1. Acute Infusion Related Reaction Secondary to the Infusion of Allogeneic 
GDA-201 Cell Product and Other Study Treatment 
Although infusion of donor lymphocytes has not been associated with acute allergic reactions, 
patients will be closely watched for the occurrence of hypotension, dyspnea and angioedema 
during and immediately after the infusion. 
The GDA-201 infusion will be stopped if a severe infusion related reaction occurs (such as 
anaphylaxis or acute compromise to a critical organ system).   
 


 
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11.5.2.2. Vascular Leak Syndrome (Systemic capillary leak syndrome) 
Neither administration of allogeneic NK cells nor autologous IL-15 activated NK infusions 
have been associated with vascular leak syndrome in previous experience. Nevertheless, 
patients will be monitored for weight gain and pulmonary edema during IL-2 administration. 
11.5.2.3. Tumor Lysis Syndrome  
Tumor lysis syndrome is as a possible risk of any therapy for active hematologic malignancy. 
All patients (except those with known allergy) are to receive allopurinol 300 mg daily 
beginning before chemotherapy and continuing until Day +7 or as clinically indicated. 
11.5.2.4. Prolonged Marrow Suppression 
The lymphodepleting chemotherapy regimen may be associated with pancytopenia. Anemia 
and thrombocytopenia are expected in all patients receiving LD, who will receive standard 
supportive transfusion care or as modified based on clinical parameters. Prolonged anemia or 
thrombocytopenia are not unexpected. 
For prolonged neutropenia, recommended management is as follows: 
• 
Days –7 to +14: In the absence of severe, uncontrolled infection, G-CSF or 
granulocytes should be avoided. If the clinical situation warrants growth factor use, 
then any remaining IL-2 administration will be stopped. 
• 
At Day +14: If the ANC is <500, G-CSF will be initiated. Begin G-CSF 5 mcg/kg 
on Day +14 only if ANC < 500 and continue until ANC > 1500 x 2 days. 
• 
Marrow aplasia at Day 35 will trigger a safety assessment by the SSC. 
11.5.2.5. Immune Mediated Syndromes  
Immunologically mediated syndromes such as cytokine release syndrome (CRS), neurotoxicity 
(encephalopathy and seizure) or macrophage activation syndrome (MAS) have been rarely 
observed after NK cell infusion; however, patients will be monitored closely for 28 days 
including monitoring CRP and ferritin. Treatment of CRS, neurotoxicity and MAS will follow 
standard guidelines which were developed for chimeric antigen receptor T cell 
therapies(Neelapu et al. 2018). 
11.5.3. 
Management of IL-2 Toxicity 
To reduce the intensity of fever and chills, pre-medication with acetaminophen/paracetamol 
500-1000 mg PO and diphenhydramine 25-50 mg PO/IV before and 4 hours after each dose of 
IL-2 is recommended. 
• Grade 3 toxicity: if the toxicity resolves to grade 2 or better within 48 hours, the IL- 
2 can be resumed at a reduced dose (4 million units or 2 million units/m2 if < 45 
kg). If the same toxicity persists, worsens or recurs, the IL-2 must be permanently 
discontinued 
• Grade 4 toxicity: permanently discontinue IL-2 
 


 
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12. 
STATISTICAL CONSIDERATIONS 
A formal Statistical Analysis Plan (SAP) will be prepared and finalized before the database 
lock for the clinical study report. The SAP will provide further technical details regarding the 
definition of analysis populations, analysis variables, and analysis methodology to meet all 
study objectives. 
12.1. 
Design and Sample Size Considerations 
The Phase I portion of the study is a conventional 3 + 3 design with four sequential dose 
cohorts. The starting dose will be 2.5 x 107 cells/kg. If all cohorts are completed, 24 patients 
will have been treated with a maximum of 6 patients per cohort. The goal is to determine the 
recommended phase II dose (RP2D) during the escalation phase. Phase I patients who are not 
evaluable for DLT may be replaced. 
At the discretion of the study sponsor, after the dose escalation phase across the four doses is 
complete, up to an additional 12 patients enrolled in backfilled cohorts may be treated to further 
characterize the DLT and safety profiles by histology (follicular lymphoma or 
DLBCL/HGBCL) at one or two dose levels prior to the phase II expansion. This will be 
designated as “backfilling” a cohort in order to ensure that the cohort enrolls a minimum of 3 
patients per histology. With the addition of these backfill patients, the MTD and/or RP2D may 
be determined. The RP2D may be different by histology (follicular lymphoma or 
DLBCL/HGBCL). 
For each cohort in the Phase II portion of the study, a Simon’s optimal 2-stage design will be 
employed based on the ORR (CR or PR) endpoint.  
 
• In the FL cohort, 11 patients will be enrolled in the first stage. If ≥3 patients achieve 
ORR, it will continue to enroll an additional 21 patients in the second stage for a total 
of 32 patients in the cohort. At the end of stage 2, if ≥10 out of the 32 patients achieve 
ORR, it is considered promising for further evaluation. This design has 80% power to 
test the null hypothesis of 20% response rate against the alternative hypothesis of 40% 
with a 1-sided type 1 error rate not exceeding 0.075 
• In the DLBCL/HGBCL cohort, 14 patients will be enrolled in the first stage. If ≥3 
patients achieve ORR, it will continue to enroll an additional 17 patients in the second 
stage for a total of 31 patients in the cohort. At the end of stage 2, if ≥8 out of the 31 
patients achieve ORR, it is considered promising for further evaluation. This design has 
80% power to test the null hypothesis of 15% response rate against the alternative 
hypothesis of 33% with a 1-sided type 1 error rate not exceeding 0.075 
 
Phase II patients who are not evaluable for response may be replaced. Patients who have at 
least one efficacy evaluation following GDA-201 infusion will be considered evaluable for 
response. 
12.2. 
Study Endpoints 
12.2.1. 
Primary Endpoints 
• Phase I: DLT and safety 


 
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• Phase II: Overall response rate (ORR) based on investigator assessments 
12.2.2. 
Secondary Endpoints 
Phase I: ORR based on investigator assessments  
Phase II: 
• ORR based on Independent Radiological Review Committee (IRRC) 
• Duration of response (DOR) 
• Progression free survival (PFS) 
• Overall survival (OS) 
• Safety and tolerability 
12.2.3. 
Exploratory Endpoints 
• 
 
 
 
 
12.3. 
Analysis Population 
DLT evaluable population: All patients who receive any amount of GDA-201 and are enrolled 
in the dose escalation part of the study. Patients without experiencing DLT who discontinue 
study prior to Day 28 for reasons other than toxicity may be replaced and excluded from the 
DLT evaluable population. 
Safety analysis population: All patients who receive any amount of GDA-201. All safety 
analyses other than the DLTs will be based on the safety analysis population.  
Efficacy evaluable population: All patients in the safety population who have at least one 
efficacy assessment after GDA-201 treatment. The efficacy evaluable population will be used 
for efficacy analyses. 
12.4. 
Patient Disposition 
The number of patients screened, enrolled and who received investigational product, will be 
summarized overall and by cohort assignment for all patients. For each analysis population, 
the number of patients included in the population will be presented. Disposition data will be 
presented based on all patients entered. 
Patient discontinuations will be listed including the date of treatment discontinuation, reason 
for treatment discontinuation, exposure to investigational product, study discontinuation, and 
reason for study discontinuation. 
Protocol deviations will be summarized and listed by patient. 
12.5. 
Baseline Characteristics 
Descriptive summary statistics will be provided for demographic variables (age, sex, race, 
ethnicity) and baseline disease characteristics (e.g., performance status). Relevant medical 
history and prior anti-cancer therapies/medications will also be summarized. 


 
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12.6. 
Safety Analysis 
12.6.1. 
Safety Alert Criteria 
The data emerging from this study will be reviewed periodically by the Study Steering 
Committee (SSC) and recommendations will be provided to the sponsor. 
Ongoing safety assessment guidelines will be used to monitor the following events, and alert 
the SSC. A safety alert will be triggered if one of the following criteria is met:  
1. Any death not related to disease progression 
2. Grade 4 or above cardiac, CNS or pulmonary DLT in 2 subjects, that is at least 
possibly related to GDA-201 
3. Any DLT occurring in Dose level 1 
4. Grade 5 adverse event that is probably or directly related to GDA-201 
5. Grade III-IV acute GvHD crossing the thresholds based on a Bayesian continuous 
monitoring model (Thall and Simon 1994)(Zhu 2016). The model assumes the 
background rate of the Grade III-IV acute GvHD is 5% with a prior beta distribution 
of beta (1,19). A prior distribution of beta (0.1,0.9) is assumed for the GDA-201 
treated patients in the study. An alert will be triggered if there is a high posterior 
probability (greater than 80%) that the Grade III-IV acute GvHD rate is 3% higher 
than the background rate. For example, if 2 patients have experienced a Grade III-IV 
GvHD, and the number of patients treated are less or equal to 11, an alert is triggered.  
 
Table 7: 
 Alert threholds based on Grade III-IV acute GvHD 
Number of patients with Grade III-IV acute 
GvHD observed 
Alert triggerd if the number of patients 
treated is ≤ to the number indicated 
1 
≤ 3 
2 
≤ 11   
3 
≤ 19   
4 
≤ 28   
5 
≤ 36   
 
If an alert occurs, accrual to the study will be temporarily halted. The SSC will consider the 
data in depth and make recommendations to the sponsor. It is understood that SSC 
recommendations to the sponsor are not binding and that the sponsor is the sole party 
responsible for final decisions regarding modification or continuation of the trial. 
12.6.2. 
Analysis of AEs and Laboratory Values 
All AEs will be coded to a system organ class (SOC) and a preferred term (PT) based on the 
Medical Dictionary for Regulatory Activities (MedDRA) version 21.0 or later.  
Patient incidence of all AEs, SAEs, AEs leading to discontinuation of treatment, and fatal AEs 
will be tabulated by SOC and PT. 


 
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The number and percent of patients reporting AEs will be evaluated overall and by dose level 
and will also be tabulated by severity and relationship to study treatment. The severity of each 
AE will be graded using The Common Terminology Criteria for Adverse Events (CTCAE) 
version 5.0 or later criteria. 
For the Phase I portion of the study, DLTs (if any) will be summarized by dose and will be 
listed separately.  
Changes in laboratory values and vital signs will be summarized with descriptive statistics. Use 
of concomitant medications, levels of GDA-201 cells in blood and incidence of anti-HLA 
antibodies will also be summarized. 
12.7. 
Efficacy Analysis 
The primary analysis for efficacy will be based on the cohort-specific efficacy evaluable 
analysis population. Sensitivity analyses may include pooling additional patients treated in 
phase I at the same dose level.  
The ORR endpoint is defined as the incidence of either a complete response (CR) or a partial 
response (PR) by the Lugano response criteria as determined by the study investigators. All 
patients that do not meet the criteria for an objective response by the analysis cutoff date will 
be considered non-responders. 
For the ORR endpoint, the Clopper-Pearson 85% and 95% confidence intervals (CIs) will be 
calculated. Confidence intervals adjusting for the 2-stage nature of the design may also be 
provided. Duration of response (DoR) will be calculated among responders (CR and PR). The 
Kaplan-Meier method will be used to estimate median DoR and the confidence intervals. 
Patients who continue to respond at the time of the analysis will be censored at the last 
assessment of response.  
Progression-free survival (PFS) is measured from the date of first GDA-201 dose until the date 
when PD is first observed per the Lugano response criteria as determined by the study 
investigators, or death from any cause, whichever is earlier. Patients without PD or death will 
be censored at the last available tumor assessment. PFS will be summarized using the Kaplan-
Meier method. 
Overall survival (OS) is measured from the date of first GDA-201 dose until death. Patients 
who are alive will be censored at the last known alive date. OS will be summarized using the 
Kaplan-Meier method. 
Sensitivity analyses of the ORR and PFS based on the assessments by the IRRC will also be 
provided.  
12.8. 
Timing of analyses 
For the phase I portion of the study, dose escalation recommendations will be made by the SSC 
for each dose cohort.  
Periodic safety reviews will also be performed during the phase II portion of the study. For 
each cohort in the phase II portion, the ORR will be calculated and evaluated at the end of stage 


 
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1 following the Simon’s 2-stage rule outlined in Section 12.1. The recommendation to proceed 
to stage 2 will be made by the SSC.   
The primary safety and efficacy analyses of the study will be conducted after all patients have 
completed the main study follow-up, one year after the initial GDA-201 infusion. Additional 
follow-up data will be collected but are beyond the scope of the primary analyses. 
A summary of those results shall be submitted to the appropriate regulatory agency(ies) 
according to local regulations. 
12.9. 
Long Term Follow Up  
For patients who received GDA-201, completed the one year study follow-up and enrolled in 
the observational long term follow-up sub-study, long-term outcomes will be collected at 2 
years, 3 years, 4 years, 5 years and 6 years post GDA-201 infusion.  
The overall research goals for this sub-study are: 
▪ Describe survival, time to relapse and progression free survival 
PFS and OS, will be assessed with a Kaplan-Meier curve with 2-sided 95% confidence 
intervals.  
12.10. 
End of Study 
End of the main study will be when all patients complete their participation in the study (Visit 
Day 365 or early Termination Visit). 
End of Long Term Follow Up sub-study will be when all patients complete their last follow up 
visit (Year 6 or earlier). 


 
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13. 
TUMOR DEFINITIONS AND ASSESSMENT  
 
Tumor measurements will be performed by PET-CT radiologic imaging techniques at baseline 
and at 28, 90, 180 and 365 days. The Lugano response criteria will be used to evaluate the 
response. 
Response and progression will be also assessed by Fluorodeoxyglucose-Positron Emission 
Tomography (FDG-PET) scan, using the response criteria outlined in the Lugano Response 
Criteria. 
For phase II an independent, central radiology review may be implemented. 
Refer to (Cheson et al. 2014) the full disease response criteria according to the Lugano 
Classification (see Appendix C). 
13.1. 
Metabolic Criteria 
13.1.1. 
Complete Response (CR) 
Complete metabolic response requires all of the following: 
• A score of 1, 2, or 3 with or without a residual mass on a PET 5 point scale; and 
• Disappearance of any previously non-measured lesions; and 
• No new lesions; and 
• No evidence of FDG-avid disease in the marrow. 
13.1.2. 
Partial Response (PR) 
Partial metabolic response requires all of the following: 
• A score of  4 or 5 on a PET 5 point scale with reduced uptake compared with 
baseline; and 
• No new lesions. 
13.1.3. 
Stable Disease 
Does not meet metabolic criteria for complete response, partial response, or progressive 
disease. 
13.1.4. 
Progressive Disease (after Partial Response, Stable Disease), 
Relapsed Disease (after Complete Response) 
Metabolic progression or relapse requires at least one of the following: 
• A score of 4 or 5 on a PET 5 point scale with increased uptake compared with 
baseline; or 
• Any new FDG-avid foci consistent with lymphoma; or 
• New or recurrent FDG avid foci in the bone marrow. 
13.2. 
Radiographic Response Criteria 
The following acronyms are used in the radiographic response criteria provided below: 


 
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LDi: longest transverse diameter of a lesion 
SDi: shortest axis perpendicular to the LDi 
SPD: sum of the product of the perpendicular diameters for multiple lesions 
PPD: cross product of the LDi and perpendicular diameter 
13.2.1. 
Complete Response 
Complete radiographic response requires all of the following: 
• All target nodes / nodal masses must have regressed as measured by CT to ≤ 1.5 cm in 
longest diameter; and 
• Disappearance of any previously non-measured lesions; and 
• No extralymphatic sites of disease; and 
• No organomegally. 
Normal morphology of bone marrow is also required for a complete radiological response if 
the marrow was an involved site. Immunohistochemical stains must be negative if 
morphology is indeterminate. 
13.2.2. 
Partial Response 
Partial radiographic remission requires all of the following: 
• ≥ 50% decrease in the SPD of up to 6 target measurable nodes and extranodal sites 
(For lesions too small to measure on CT, assign 5mm x 5mm as the default value and 
then 0 mm x 0 mm when the lesion is no longer visible. For a node >5 mm x 5 mm, 
but smaller than normal, use the actual measurement of the node for calculations); and 
• No increase in the size of previously non-measurable lesions; and 
• No new lesions. 
If splenomegaly is present, a > 50% decrease in spleen length is also required to report a 
partial radiological response 
13.2.3. 
Stable Disease 
Does not meet radiographic criteria for complete response, partial response, or progressive 
disease. 
13.2.4. 
Progressive Disease (after Partial Response, Stable Disease), 
Relapsed Disease (after Complete Response) 
Radiographic progression or relapse requires at least one of the following: 
• An individual node must be abnormal with: 
o LDi >1.5 cm; and 
o ≥ 50% increase from nadir in the PPD; or 
• An increase in LDi or SDi from nadir 


 
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o ≥ 0.5 cm increase in LDi or SDi from nadir for any lesion ≤ 2cm; or 
o ≥ 1.0 cm increase in LDi or SDi from nadir for any lesion > 2 cm; or 
• A 50% increase in spleen length compared to its prior increase beyond baseline; or 
• New or recurrent splenomegally; or 
• Clear progression of pre-existing non-measured lesions; or 
• Regrowth of any previously resolved lesions; or 
• A new node > 1.5 cm in any axis; or 
• A new extranodal site > 1.0 cm in any axis or if < 1.0 cm in any axis, its presence 
must be unequivocally attributable to lymphoma; or 
• Assessable disease of any size unequivocally attributable to lymphoma; or 
• New or recurrent involvement of the bone marrow. 
13.3. 
Definitions 
1. Measurable disease:  
FDG-avid lesions characterized by a Deauville score of 4-5 and which coincide with previously 
documented disease foci, or foci which are highly suspicious for lymphoma involvement, or 
• Bidimensionally measurable lesions with clearly defined margins by:  
a. medical photograph (skin or oral lesion), or plain X-ray with at least one 
diameter 0.5 cm or greater (bone lesions are not included) or 
b. computed tomography (CT), magnetic resonance imaging (MRI) or other 
imaging scan with both diameters greater than the distance between cuts of the 
imaging study, or  
c. palpation with both diameters 2 cm or greater 
2. Evaluable disease: unidimensionally measurable lesions, masses with margins not 
clearly defined, lesions with both diameters less than 0.5 cm, lesions on scan with either 
diameter smaller than the distance between cuts, palpable lesions with either diameter 
less than 2 cm, bone disease. 
3. Non-evaluable diseases: pleural effusions, ascites, disease documented by indirect 
evidence only. 
4. Objective status: to be recorded at each evaluation. If an organ has too many measurable 
lesions to measure at each evaluation, choose three to be followed before the patient is 
entered on study. The remaining measurable lesions in that organ will be considered 
evaluable for the purpose of objective status determination. Unless progression is 
observed, objective status can only be determined when all measurable and evaluable 
sites and lesions are assessed.  
 


 
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14. 
TREATMENT COMPLIANCE 
The Investigator will document the time and dose of all administrations in the patient’s medical 
notes and also record this information in the electronic case report form (eCRF). Any reasons 
for non-compliance will also be documented including: 
• Missed visits 
• Interruptions in the schedule of administration  
• Non-permitted medications 


 
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15. 
ASSESSMENT OF SAFETY 
All patients will be assessed for safety by monitoring AEs, clinical laboratory tests, vital signs, 
physical examinations and anti-drug antibody (anti-donor HLA) testing.   
15.1. 
Relationship to Study Drug 
15.1.1. 
Adverse Event (AE) 
An AE is any untoward medical occurrence in a patient administered a pharmaceutical product, 
which does not necessarily have a causal relationship with the treatment. An AE can be any 
unfavorable and unintended sign (e.g., including an abnormal laboratory finding), symptom, or 
disease temporally associated with the use of the study drug, whether or not it is considered to 
be study drug related. This includes any newly occurring event or previous condition that has 
increased in severity or frequency since the administration of study drug (treatment-emergent). 
15.1.2. 
Serious Adverse Event (SAE) 
A serious adverse event (SAE) is any AE, occurring at any dose level and regardless of 
causality that: 
1. Results in death 
2. Is life-threatening: Life-threatening means that the patient was at immediate risk of 
death from the reaction as it occurred, (i.e., it does not include a reaction which 
hypothetically might have caused death had it occurred in a more severe form) 
3. Requires inpatient hospitalization or prolongation of existing hospitalization  
4. Results in persistent or significant disability/incapacity 
5. Is a congenital anomaly/birth defect 
6. Is an important medical event: an important medical event is an event that may not 
result in death, be life-threatening, or require hospitalization but may be considered an 
SAE when, based upon appropriate medical judgment, it may jeopardize the patient and 
may require medical or surgical intervention to prevent one of the outcomes listed in 
the definitions for SAEs. Examples of such medical events include allergic 
bronchospasm requiring intensive treatment in an emergency room or at home, blood 
dyscrasias or convulsions that do not result in inpatient hospitalization, or the 
development of drug dependency or drug abuse 
Note: A hospitalization for an elective procedure will not be considered a SAE  
 
For the purpose of this study, Progressive Disease and/ or Relapse and / or any events 
that are unequivocally related to PD and / or Relapse  are expected outcomes of the 
subject’s disease and therefore are not considered SAEs and do not  require SAE 
reporting, unless life-threatening or fatal. 
15.1.3. 
Unexpected Adverse Event (AE) 
An unexpected AE is an AE that is not reported in the Investigator’s Brochure (IB). 


 
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15.1.4. 
Relationship of Adverse Events (AEs) to Study Drug 
The following classifications should be used when evaluating the relationship of AEs and SAEs 
to the investigational drug. 
1. None: No relationship between the experience and the administration of study drug; related 
to other etiologies such as concomitant medications or patient’s clinical state 
2. Unlikely: The current state of knowledge indicates that a relationship is unlikely   
3. Possibly: A reaction that follows a plausible temporal sequence from administration of the 
study drug and follows a known response pattern to the suspected study drug. The reaction 
might have been produced by the patient’s clinical state or other modes of therapy 
administered to the patient 
4. Probably: A reaction that follows a plausible temporal sequence from administration of the 
study drug and follows a known response pattern to the suspected study drug. The reaction 
cannot be reasonably explained by the known characteristics of the patient’s clinical state 
or other modes of therapy administered to the patient 
5. Definitely: A reaction that follows a plausible temporal sequence from administration of 
the study drug and follows a known response pattern to the suspected study drug and can 
be confirmed with a positive re-challenge test or supporting laboratory data 
15.1.5. 
AE Severity 
15.2. 
Grade refers to the severity of the AE. The CTCAE displays 
Grades 1 through 5 with unique clinical descriptions of severity 
for each AE based on general guideline described in CTCAE 
version 5.0.Procedures for Adverse Event (AE) Recording and 
Reporting 
Patients will be evaluated and questioned generally for AE/SAE during the course of the study. 
The Medical History eCRF should be comprehensive of patient’s medical history up to Day -
10 when study treatment starts.  
Any event after written informed consent has been obtained and prior to study treatment 
initiation should be recorded as medical history unless the event is directly related to a 
screening procedure, in such case it would be considered an AE/SAE and documented on the 
AE/SAE eCRF. 
All AEs/SAEs occurring from initiation of study treatment (first dose of Rituximab) until the 
End of Study visit are to be documented on the AE/SAE eCRF.  
When new significant information is obtained as well as when the outcome of an event is 
known, the Investigator should record the information on a new SAE form. If the patient was 
hospitalized, a copy of the discharge summary must be included as part of the patient medical 
file. In all instances, the Investigator should follow up with patients until the outcome of the 
SAE is known. 
All AEs spontaneously reported by the patient and/or in response to an open question from 
study personnel or revealed by observation, physical examination or other diagnostic 
procedures will be recorded on the AE eCRF. Any clinically relevant change in laboratory 


 
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assessments or other clinical findings is considered an AE and must be recorded on the AE 
eCRF. All AEs are to be followed until the event resolves or the clinical course is stabilized. 
For SAEs, a SAE form must be completed with as much information as possible and submitted 
in the time frame described below. 
On discovery, all SAEs should be immediately reported (latest within 24 hours of knowledge 
of the event) to Parexel Safety Services by: 
- 
Entering the AE in the appropriate section (AE page and/or SAE page) of the eCRF, 
indicating that the event is considered serious, and providing all the details per the eCRF 
completion guidelines. 
- 
Completing the SAE Report Form and transmitting the documents to Parexel MSS, 
using direct transmission, the appropriate regional Parexel SAE fax number or email 
address below: 
- 
For non-US sites - France (Paris) Fax: +33 1 44 90 32 75 or +33 1 44 90 35 34 
- 
For US sites - North America (Billerica) fax: +1 781 434 5957 
- 
Global: Medical_Paris@parexel.com  
- 
-              In the event that the site is unable to complete the SAE form to report the 
event within 24 hours of their knowledge of the event, the investigators may report 
the SAE over the telephone via the SAE answering service, and then transmit the 
completed SAE form via direct transmission, fax or email, If questions arise regarding 
the reporting procedures or the specifics of the reporting of an event, sites may call 
utilizing the following number: 
- 
For non-US sites - France (Paris) Phone: +33 1 44 90 32 90 
For US sites - North America (Billerica) phone: +1 781 434 5010 If there are serious, 
unexpected AEs associated with the use of the study drug, Parexel will notify the appropriate 
regulatory agency(ies) including reporting to the Eudravigilance database and all appropriate 
parties on an expedited basis. It is the responsibility of the Investigator to promptly notify the 
Institutional Review Board (IRB)/Ethics Committee (EC) of all unexpected SAEs involving 
risk to human patients. 
15.3. 
Other Required Safety Assessments  
A clinically significant worsening from Baseline of any abnormal study assessment, such as 
laboratory test, physical examination, or vital signs, should be considered an AE and recorded 
accordingly. If possible, a diagnosis for the clinically significant study assessment should be 
provided by the Investigator (e.g., urinary tract infection or anemia). In the absence of a 
diagnosis, the abnormal study assessment itself should be listed as the AE (e.g., bacteria in 
urine or decreased hemoglobin).  
An abnormal study assessment is considered clinically significant if the patient has one or more 
of the following related to the abnormal study assessment: 
1. Concomitant clinical signs or symptoms  
2. Further diagnostic testing or medical/surgical intervention 
3. A change in the dose of study drug or patient discontinued from the study 
Repeat testing to determine whether the result is abnormal, in the absence of any of the above 
criteria, does not necessarily meet clinically significant criteria. The determination of whether 


 
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the study assessment results are clinically significant will be at the discretion of the 
Investigator.  
15.4. 
Pregnancy  
15.4.1. 
 
Pregnancy Reporting 
Details of all pregnancies occurring in female participants or female partners of male 
participants will be collected after the start of study intervention and until delivery if pregnancy 
consent has been obtained. 
If a pregnancy is reported, the Investigator should record the information on the appropriate 
form and submit it to Parexel Safety Services within 30 days of learning of the pregnancy. The 
Investigator must follow-up and document the course and the outcome of all pregnancies even 
if the patient was discontinued from the study or if the study has finished. 
While pregnancy itself is not considered to be an AE or SAE, any pregnancy complication or 
elective termination of a pregnancy will be reported as an AE or SAE.  Abnormal pregnancy 
outcomes (e.g. spontaneous abortion, foetal death, stillbirth, congenital anomalies, ectopic 
pregnancy) are considered to be SAEs. Any post-study pregnancy-related SAE considered 
reasonably related to study drug by the Investigator will be reported to the Sponsor.  While the 
Investigator is not obligated to actively seek this information in former study participants, he 
or she may learn of an SAE through spontaneous reporting. 
Any pregnancy related SAE that occurs during pregnancy (including SAEs occurring after last 
administration of study drug) must be recorded on the SAE report form (e.g., maternal serious 
complications, spontaneous or therapeutic abortion, ectopic pregnancy, stillbirth, neonatal 
death, congenital anomaly, or birth defect) and reported within 24 hours in accordance with the 
procedure for reporting SAEs. 
The pregnancy will be followed to determine the outcome. The Investigator will collect any 
follow-up information on the participant/participant’s partner and the neonate and the 
information will be forwarded to Parexel.  Generally, follow-up will not be required for longer 
than 6 to 8 weeks beyond the estimated delivery date.  Any termination of the pregnancy will 
be reported, regardless of foetal state (presence or absence of anomalies) or indication for the 
procedure. All outcomes of pregnancy must be reported by the Investigator to Parexel on the 
appropriate form within 30 days after he or she has gained knowledge of the spontaneous or 
elective abortion or delivery of the baby. 
Any female participant who becomes pregnant while participating in the study will discontinue 
study drug or will be withdrawn from the study. 
15.4.2. 
Females of Childbearing Potential and Contraception 
A woman is considered of childbearing potential (ie, fertile) after menarche and until 
becoming postmenopausal unless surgically sterilized.  Surgical sterilization methods include 
hysterectomy, bilateral salpingectomy, bilateral tubal ligation and bilateral oophorectomy. 
 


 
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Contraception methods should be used from the time of screening pregnancy test and for ≥ 
4 months after the last dose of GDA-201. 
Contraception methods include the following: 
• Combined (estrogen- and progestogen containing) hormonal contraception associated 
with the inhibition of ovulation 
− Oral, intravaginal, or transdermal 
• Progestogen-only hormonal contraception associated with the inhibition of ovulation 
− Oral, injectable, implantable 
• An intrauterine device 
• Intrauterine hormone-releasing system 
• Bilateral tubal occlusion 
• Vasectomized partner (provided that the vasectomized partner is the sole sexual partner of 
the woman of childbearing potential study participant and that the vasectomized partner 
has received medical assessment of surgical success) 
• Sexual abstinence (defined as refraining from heterosexual intercourse) 
Total sexual abstinence should only be used as a contraceptive method if it is in 
line with the patients’ usual and preferred lifestyle.  Periodic abstinence (eg, 
calendar, ovulation, symptothermal, postovulation methods), declaration of 
abstinence for the duration of exposure to investigational medicinal product, and 
withdrawal are not acceptable methods of contraception. 
Of note, barrier contraception (including male and female condoms with or without 
spermicide) is not considered a highly effective method of contraception, and, if used, this 
method must be used in combination with another acceptable method listed above. 
If a woman of childbearing potential is using hormonal contraceptives such as birth control 
pills or devices, a second barrier method of contraception (eg, condoms) must also be used. 
A postmenopausal state is defined as no menses for 12 months without an alternative medical 
cause. A high follicle-stimulating hormone level in the postmenopausal range may be used to 
confirm a postmenopausal state in women not using hormonal contraception or hormonal 
replacement therapy.  However, in the absence of 12 months of amenorrhea, a single follicle 
stimulating hormone measurement is insufficient. 
 


 
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16. 
SPECIAL REQUIREMENTS AND PROCEDURES 
16.1. 
Study Monitoring  
The Clinical Monitor will arrange to visit the Investigator sites at regular intervals during the 
study.  The monitoring visits must be conducted according to the applicable International 
Conference on Harmonisation (ICH) and Good Clinical Practice (GCP) guidelines to ensure 
protocol adherence, quality of data, drug accountability, compliance with regulatory 
requirements, and continued adequacy of the investigational site and its facilities. During these 
visits, eCRFs and other data related to the study will be reviewed and any discrepancies or 
omissions will be resolved. The Clinical Monitor will be given access to study relevant source 
documents (including medical records) for purposes of source data verification. 
During and/or after completion of the study, quality assurance officers named by Gamida Cell 
or the regulatory authorities may wish to perform on-site audits. The Investigator is expected 
to cooperate with any audit and provide assistance and documentation (including source data) 
as requested. 
16.1.1. 
Audits and Inspections  
The Investigators and clinical sites will permit trial related monitoring, audits, IRB review, and 
regulatory inspections as requested by regulatory health authorities, Gamida Cell or designee, 
including direct access to source data/documents (i.e., original medical records, laboratory 
reports, hospital documents, progress reports, signed ICFs, etc.) in addition to eCRFs. 
16.1.2. 
Data Quality Control and Quality Assurance 
The Investigator is responsible for ensuring the study is conducted according to the protocol, 
Code of Federal Regulations (CFR), GCP, and applicable regulatory requirements. The 
responsibilities outlined in these documents along with the identification that a signed informed 
consent must be obtained prior to a patient participation in the study. 
16.2. 
Confidentiality 
To maintain patient privacy, all eCRFs, study drug accountability records, study reports and 
communications will identify the patient by the assigned patient identification number. The 
Investigator will grant monitor(s) and auditor(s) from Gamida Cell or designee and regulatory 
authority(ies) access to the patient’s original medical records for verification of data gathered 
on the eCRFs and to audit the data collection process. The patient’s confidentiality will be 
maintained and will not be made publicly available to the extent permitted by the applicable 
laws and regulations. 
All information regarding the investigational product supplied by Gamida Cell to the 
Investigator is privileged and confidential information. The Investigator agrees to use this 
information to accomplish the study and will not use it for other purposes without consent from 
Gamida Cell. It is understood that there is an obligation to provide Gamida Cell with complete 


 
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CLIENT CONFIDENTIAL 
data obtained during the study. The information obtained from the clinical study will be used 
towards the development of the investigational product and may be disclosed to regulatory 
authority(ies), other Investigators, corporate partners, or consultants as required. 
16.2.1 Publication Policy  
The sponsor will review the data periodically, and the results of this study may be presented at 
one or more medical congresses and/or published in scientific journals. After completion of the 
study, the sponsor will prepare a clinical study report based on data from all participating 
countries. This study and its results may be submitted for inclusion in appropriate health 
authority study registries, as well as publication on health authority study registry websites, as 
required by local health authority regulations. 
16.3. 
Protocol Amendments 
Protocol amendments that impact patient safety, change the scope of the investigation, or affect 
the scientific quality of the study must be approved by the IRB/IEC and submitted to the 
appropriate regulatory authorities before implementation of such modifications to the study. 
In the event that the protocol needs to be modified immediately to eliminate an apparent hazard 
to a patient, Gamida Cell will amend and implement the protocol change and subsequently 
notify the regulatory authorities and/or the IRB/IEC, as appropriate. 
The Investigator should not modify the protocol without agreement from Gamida Cell and prior 
review or approval by the IRB/IEC. Any deviations from the protocol should be documented 
by the Investigator or designee.  
16.4. 
Obligations of the Principal Investigator 
16.4.1. 
Institutional Review Board (IRB)/Independent Ethics Committee 
(IEC) 
The Investigator must obtain written IRB/IEC approval of the protocol, approval for relevant 
supporting information and all types of patient recruitment and advertisement and the ICF prior 
to starting the study. The IRB/IEC will meet all local regulatory requirements governing 
IRBs/IECs. 
Gamida Cell or the designee must approve the ICF submitted to the investigational site’s 
IRB/IEC. All patient recruitment and advertisements must be submitted to Gamida Cell or 
designee prior to submission to the IRB/IEC, for review.  
16.4.2. 
Ethical Conduct of the Study 
 
Gamida Cell and the Investigator must comply with all instructions, regulations, and 
agreements in this protocol and in the applicable ICH and GCP guidelines and must also 
conduct the study in accordance with local regulations.   


 
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16.4.3. 
Written Informed Consent 
 
Written informed consent is required from each patient prior to any testing under this protocol, 
including screening tests and evaluations. The ICF, as specified by the investigational site’s 
IRB/IEC, must follow the Protection of Human Subjects regulations.   
The background of the proposed study and the benefits and risks of the procedures and study 
must be explained to the patients. It is the responsibility of the Investigator to obtain consent 
and to provide the patient with a copy of the signed and dated ICF. Confirmation of a patient’s 
informed consent must also be documented in the patient’s medical record prior to any testing 
under this protocol, including screening tests and evaluations. 
All ICFs used in this study must be approved by the appropriate IRB/IEC and by Gamida Cell 
or designee. The ICF must not be altered without the prior agreement of the relevant IRB/IEC 
and Gamida Cell.   
16.4.4. 
Patient Data Protection  
 
The participants will be informed that their personal study-related data (including explanation 
on the level of disclosure) will be used by the sponsor in accordance with local data 
protection law. The participants will be required to give consent for their data to be used as 
described in the informed consent.  
All parties will comply with all applicable laws, including laws regarding the implementation 
of organizational and technical measures to ensure protection of participants personal data. 
Such measures will include omitting participant names or other directly identifiable data on 
any blood collection tubes, sponsor forms, reports, publications, or in any other disclosures, 
except where required by applicable laws.  
Personal data will be stored at the study site in encrypted electronic and/or paper form and 
will be stored in a secure location.  
In the event of a potential personal data breach, the study site shall be responsible for 
determining whether a personal data breach has in fact occurred and, if so, providing breach 
notifications as required by law.  
To protect the rights and freedoms of natural persons with regards to the processing of 
personal data, when study data are compiled for transfer to sponsor and other authorized 
parties, participant names will be removed and will be replaced by a single, specific 
participant code. All other identifiable data transferred to the sponsor or other authorized 
parties will be identified by this single, participant-specific code.  
The investigator site will maintain a confidential list of participants who participated in the 
study, linking each participant’s numerical code to his actual identity. The participants will be 
informed that their medical records may be examined by Clinical Quality Assurance auditors 
or other authorized personnel appointed by the sponsor, [by appropriate IRB/IEC members,] 
and by inspectors from regulatory authorities. 


 
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17. 
DATA HANDLING AND RETENTION OF RECORDS 
17.1. 
Electronic Case Report Form Completion 
 
eCRFs will be completed for each enrolled patient. It is the Investigator’s responsibility to 
ensure the accuracy, completeness, and timeliness of the data reported in the patient’s eCRF. 
Source documentation supporting the eCRF data should indicate the patient’s participation in 
the study and should document the dates and details of study procedures, AEs, and patient 
status. 
Investigators will maintain copies of the eCRFs at the clinical site. For patients who discontinue 
or terminate from the study, the eCRFs will be completed as much as possible, and the reason 
for the discontinuance or termination clearly and concisely specified on the appropriate eCRF. 
17.2. 
Retention of Records 
The Investigator will maintain all study records according to ICH GCP and applicable 
regulatory requirements. Records will be retained for at least 2 years after the last marketing 
application approval or 2 years after formal discontinuation of the clinical development of the 
investigational product or according to applicable regulatory requirements. If the Investigator 
withdraws from the responsibility of keeping the study records, custody must be transferred to 
a person willing to accept the responsibility. Gamida Cell must be notified in writing if a 
custodial change occurs. 


 
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Suppl 5: v116-25. 
Tonn, T., D. Schwabe, H. G. Klingemann, S. Becker, R. Esser, U. Koehl, M. Suttorp, E. 
Seifried, O. G. Ottmann, and G. Bug. 2013. 'Treatment of patients with advanced 
cancer with the natural killer cell line NK-92', Cytotherapy, 15: 1563-70. 
Wang, L., H. Lam, Y. Shou, and A. Galaznik. 2019. 'Meta-analytical methods for estimating 
outcomes from overall response rate in patients with relapsed/refractory diffuse large 
B-cell lymphoma', Oncotarget, 10: 3285-93. 
Wiernik, P. H., I. S. Lossos, J. M. Tuscano, G. Justice, J. M. Vose, C. E. Cole, W. Lam, K. 
McBride, K. Wride, D. Pietronigro, K. Takeshita, A. Ervin-Haynes, J. B. Zeldis, and 
T. M. Habermann. 2008. 'Lenalidomide monotherapy in relapsed or refractory 
aggressive non-Hodgkin's lymphoma', J Clin Oncol, 26: 4952-7. 
Woan, K. V., and J. S. Miller. 2019. 'Harnessing Natural Killer Cell Antitumor Immunity: 
From the Bench to Bedside', Cancer Immunol Res, 7: 1742-47. 
Zhu, L.; Yao, B.; Xia, A.; Jiang, Q. 2016. 'Statistical Monitoring of Safety in Clinical Trials', 
Statistics in Biopharmaceutical Research, 8: 88-105. 
 
 


 
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APPENDIX A. PERFORMANCE STATUS SCALE AND NYHA 
CLASSIFICATION 
 ECOG PERFORMANCE STATUS SCALE 
Grade 
ECOG PERFORMANCE STATUS 
0 
Fully active, able to carry on all pre-disease performance without restriction 
1 
Restricted in physically strenuous activity but ambulatory and able to carry out 
work of a light or sedentary nature, e.g., light house work, office work 
2 
Ambulatory and capable of all selfcare but unable to carry out any work 
activities; up and about more than 50% of waking hours 
3 
Capable of only limited selfcare; confined to bed or chair more than 50% of 
waking hours 
4 
Completely disabled; cannot carry on any selfcare; totally confined to bed or 
chair 
5 
Dead 
REFERENCE 
Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, Carbone PP. Toxicity and response criteria of the Eastern 
Cooperative Oncology Group. Am J Clin Oncol. 1982 Dec;5(6):649-655. PMID: 7165009. 
NEW YORK HEART ASSOCIATION FUNCTIONAL CLASSIFICATION 
NYHA 
Class 
Symptoms 
I 
Cardiac disease, but no symptoms and no limitation in ordinary physical 
activity, e.g. shortness of breath when walking, climbing stairs etc. 
II 
Mild symptoms (mild shortness of breath and/or angina) and slight limitation 
during ordinary activity. 
III 
Marked limitation in activity due to symptoms, even during less-than-ordinary 
activity, e.g. walking short distances (20–100 m). 
Comfortable only at rest. 
IV 
Severe limitations. Experiences symptoms even while at rest. Mostly bedbound 
patients. 
REFERENCE 
The Criteria Committee of the New York Heart Association. Nomenclature and Criteria for Diagnosis of 
Diseases of the Heart and Great Vessels. 9t 
 
 
 


 
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APPENDIX B. INFECTIOUS DISEASES SOCIETY OF AMERICAS 
(IDSA) GUIDELINES ON CLEARANCE OF 
HEPATITIS B AND C INFECTION 
Hepatitis B (HBV) – Lok et al. Chronic Hepatitis B: Updated 2009. Hepatology, 
September 2009. 
Resolved hepatitis B— Previous HBV infection without further virologic, biochemical or 
histological evidence of active virus infection or disease. 
1. Previous known history of acute or chronic hepatitis B or the presence of anti-HBc 
± anti-HBs 
2. Hepatitis B surface antigen (HBsAg) negative 
3. Undetectable serum HBV DNA (very low levels may be detectable using sensitive 
PCR assays) 
4. Normal ALT levels 
HBsAg and anti-HBc testing should be performed in persons who have high risk of HBV 
infection prior to initiation of chemo- or immunosuppressive therapy. Pro-phylactic antiviral 
therapy should be administered to hepatitis B carriers (regardless of baseline serum HBV 
DNA level) at the onset of cancer chemotherapy or a finite course of immunosuppressive 
therapy, and maintained for 6 months afterwards. 
While HBV reactivation can occur in persons who are HBsAg negative but anti-HBc and 
anti-HBs positive and in those with isolated anti-HBc, this is infrequent, and there is not 
enough information to recommend routine prophylaxis for these individuals. These patients 
should be monitored and antiviral therapy initiated when serum HBV DNA becomes 
detectable. 
Hepatitis C (HCV) - https://www.hcvguidelines.org/evaluate/monitoring 
It is essential to test for HCV RNA 12 weeks (or longer) after treatment completion. 
Undetectable or unquantifiable HCV RNA 12 weeks or longer after treatment completion is 
defined as a sustained virologic response (SVR), which is consistent with cure of HCV 
infection. Virologic relapse is rare 12 weeks or longer after treatment completion. 
Nevertheless, repeat quantitative HCV RNA testing can be considered at 24 or more weeks 
after completing treatment for patients in whom ALT increases to above the upper limit of 
normal (ULN). 
 
 
 
 


 
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APPENDIX C. DEFINITIONS OF TUMOR RESPONSE (LUGANO, 
2014) 
Response 
Site 
PET-CT Metabolic 
Response 
CT Radiologic 
Response 
Complete Response 
LN and 
extralymphatic 
sites 
Score 1, 2, or 3 with or without a 
residual mass on a 5-point scale 
All of the following: 
Target LN regress to ≤ 1.5 cm 
in longest transverse diameter 
(LDi) 
No extralymphatic sites of disease 
Non-measured lesion Not applicable 
Absent 
Organ enlargement 
Not applicable 
Regress to normal 
New lesions 
None 
None 
Bone marrow 
No evidence of FDG-avid disease in 
BM 
Normal by morphology; if 
indeterminant, IHC negative 
Partial Response 
LN and 
extralymphatic sites 
Score 4 or 5† with reduced uptake 
compared 
with 
baseline 
and 
residual mass(es) of any size 
≥ 50% decrease in SPD of 
measurable LN and extranodal sites 
Non-measured lesion Not applicable 
Absent/normal, regressed, no 
increase 
Organ enlargement 
Not applicable 
Spleen must have regressed by 
>50% in length beyond normal 
New lesions 
None 
None 
Bone marrow 
Residual uptake higher than normal 
marrow but reduced compared with 
baseline 
Not applicable 
Response 
Site 
PET-CT Metabolic 
Response 
CT Radiologic 
Response 
No response or stable 
disease 
LN and 
extralymphatic sites 
Score 4 or 5 with no significant 
change in FDG uptake from baseline 
at interim or end of treatment 
< 50% decrease from baseline in 
SPD of LN or extranodal sites.  
No criteria for PD are met 
Non-measured lesion Not applicable 
No increase consistent with PD 
Organ enlargement 
Not applicable 
No increase consistent with PD 
New lesions 
None 
None 
Bone marrow 
No change from baseline 
Not applicable 


 
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Progressive Disease 
LN and 
extralymphatic sites 
Score 4 or 5 with an increase in 
intensity of uptake from baseline 
and/or new FDG-avid foci 
consistent with lymphoma 
Requires at least one of the 
following: 
LN/lesion with LDi > 1.5 cm and 
increase by ≥ 50% from PPD nadir 
and an increase in LDi or SDi from 
nadir of 0.5 cm for lesions ≤ 2 cm 
and 1.0 cm for lesions > 2 cm. 
Spleen increased length by 50%; 
new or recurrent splenomegaly, 
must increase by at least 2 cm from 
baseline. 
Non-measured lesion None 
New or clear progression of 
preexisting non-measured lesions 
New lesions 
New FDG-avid foci consistent with 
lymphoma rather than another 
etiology 
Regrowth of previously resolved 
lesions 
New LN > 1.5 cm in any axis 
New extranodal site ≥ 1.0 cm in any 
axis 
Assessable disease of any size 
unequivocally due to lymphoma 
Bone marrow 
New or recurrent FDG-avid foci 
New or recurrent involvement 
Abbreviations: LDi, longest transverse diameter of a lesion; LN, lymph nodes; FDG, fluorodeoxyglucose; IHC, 
immunohistochemistry; SPD, sum of the products of the diameters; PD, progressive disease; PPD, perpendicular 
diameter. 
†PET 5PS: 1, no uptake above background; 2, uptake ≤ mediastinum; 3, uptake > mediastinum but ≤ liver; 4, uptake 
moderately > liver; 5, uptake markedly higher than liver and/or new lesions; X, new areas of uptake unlikely to be 
related to lymphoma. 
 


 
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APPENDIX D. GVHD ASSESSMENT 
Acute GvHD Definition 
Acute GvHD will be classified according to the Consensus Conference on Acute GvHD 
grading (Przepiorka et al. 1995).  
Table 8: 
GvHD classification 
Overall Grade 
Skin 
Liver 
Gut 
I 
Stage 1-2 
None 
None 
II 
Stage 3 or 
Stage 1 or 
Stage 1 
III 
 
Stage 2-3 or 
Stage 2-4 
IV 
Stage 4 or 
Stage 4 
 
*See following table for individual organ staging. The overall grade of GvHD, however, reflects the actual 
extent of disease. For each overall grade, an assessment of skin disease plus liver and/or gut involvement is 
required. 
 
Table 9: 
Clinical manifestations and staging of acute graft versus host disease 
Organ 
Clinical Manifestations 
Staginge 
Skina 
Erythematous, maculopapular rash 
involving palms and soles; may 
become confluent 
Severe disease: bullae 
Stage 1: <25% rash 
Stage 2: 25-50% rash 
Stage 3: generalized erythroderma 
Stage 4: bullae 
Liverb 
Painless jaundice with conjugated 
hyperbilirubinemia and increased 
alkaline phosphatase 
Stage 1: bilirubin 2-3 mg/dL 
Stage 2: bilirubin 3.1-6 mg/dL 
Stage 3: bilirubin 6.1-15 mg/dL 
Stage 4: bilirubin >15 mg/dL 
Gastrointestinal tractc 
Upper: nausea, vomiting, anorexia 
Lower: diarrhea, abdominal cramps, 
distention, ileus, bleeding 
Stage 1: diarrhea >500 ml/day or 
persistent nausea, vomiting, or anorexia d 
Stage 2: diarrhea >1000 ml/day 
Stage 3: diarrhea >1500 ml/day 
Stage 4: large volume diarrhea and 
severe abdominal pain +/- ileus 
a Use ‘Rule of Nines’ or burn chart to determine extent of rash 
b Range given as TBili. Downgrade one stage if a cause of elevated bilirubin other than GvHD has been 
documented. 
c Downgrade one stage if a cause of diarrhea other than GvHD has been documented. 
d Downgrade upper GI one stage if biopsy result is negative, or if no biopsy done and GvHD is not an etiology, 
or if the biopsy is equivocal and GvHD is not an etiology. 
e Although GvHD will be assessed at every protocol-specified visit, GvHD will only be analyzed if it occurs 
after primary neutrophil engraftment. If GvHD is not an etiology for any organ, then GvHD is downgraded to 
stage 0. 
 
Chronic GvHD Definition 
 


 
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Chronic GvHD will be classified as mild, moderate, or severe, according to the National 
Institute of Health consensus grading criteriai summarized below: 
Table 10: 
NIH Global Severity of chronic GvHD 
Global Severity 
Criteria 
Mild 
1-2 organs involved with a max organ severity score of 1  
AND 
Lung score=0 
Moderate 
≥3 organs involved with a max organ severity score of 1 
OR 
Any organ (except lung) with a severity score of 2 
OR 
Lung score=1 
Severe 
Any organ with a severity score of 3 
OR 
Lung score ≥2 
Notes for global severity scoring: 
Clinical centers must reference the 2014 consensus criteria for organ specific severity grading (Jagasia et al. 
2015). A record of the organ specific scoring must be kept on file at the clinical center. See cGvHD scoring 
worksheet in the Data Management Handbook; either the provided worksheet or an equivalent EMR adaptation 
of the form (approved by the sponsor) must be used to document chronic GvHD. 
In skin: higher of the 2 scores to be used for calculating global severity. 
In lung: FEV1 is used instead of clinical score for calculating global severity. 
If the entire abnormality in an organ is noted to be unequivocally explained by a non-GvHD documented cause, 
that organ is not included for calculation of the global severity. 
If the abnormality in an organ is attributed to multifactorial causes (GvHD plus other causes) the scored organ 
will be used for calculation of the global severity regardless of the contributing causes (no downgrading of 
organ severity score). 
 
 


 
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APPENDIX E. EXPECTED TOXICITIES OF STUDY MEDICATION 
 
Rituximab  
common 
less common 
rare, but may be serious 
• mild allergic reaction 
with first infusion 
(may include fever, 
headache, chills, 
itching, hives, nausea, 
shortness of breath) 
• upper respiratory tract 
infection 
• nasopharyngitis 
• urinary tract infection 
• bronchitis 
• allergic reaction with 
second and later 
infusions (same 
symptoms as under 
common) 
• low white blood cell 
(WBC) count with 
increased risk of 
infection 
• cough 
• rash, itching 
• nausea 
• vomiting 
• diarrhea 
• muscle aches 
• runny nose 
• sinus infection 
• serious allergic reaction, 
with hives, trouble 
breathing, tightness in the 
chest or throat 
• heart attack, or shock 
• serious skin reaction 
• kidney damage 
• low platelet count with 
increased risk of 
bleeding 
• blockage or hole in the bowel, 
with abdominal (belly) pain 
• low red blood cell 
count (anemia) with 
tiredness and weakness 
• death due to allergic 
reaction, infection, lung 
damage, tumor lysis 
syndrome, serious skin rash, 
bowel obstruction, liver 
failure from reactivated 
hepatitis b, and other causes 
 
Prescribing Information for Rituximab: 
https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761088s018lbl.pdf  
 
 
 
IL-2 
common 
less common 
rare, but may be serious 
• fever 
• chills 
• skin rash 
• decreased platelet 
count 
• nausea 
• vomiting 
• diarrhea 
• low blood pressure 
• fast heart rate 
• confusion 
• shortness of breath 
• fatigue 
• tiredness 
• fluid retention 
• weight gain 
• abnormal liver function 
tests 
• infection 
• mouth sores 
• poor appetite 
• dizziness 
• dry or peeling skin 
• capillary leak syndrome 
• hypothyroidism 
• abnormal renal function tests  


 
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• low urine output 
Prescribing Information for Proleukin (IL-2): 
https://www.accessdata.fda.gov/drugsatfda docs/label/2012/103293s5130lbl.pdf  
 
r 
 


 
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Lymphodepleting Preparative Regimen (All patients) 
 
Cyclophosphamide 
Common 
Less Common 
Rare, but may be serious 
• low white blood cell 
(WBC) count with 
increased risk of 
infection 
• hair loss or thinning, 
including face and body 
hair (usually grows back 
after treatment) 
• nausea 
• vomiting 
• loss of appetite 
• sores in mouth or on lips 
• bleeding from bladder, 
with blood in urine 
• diarrhea 
• long-term or short-term 
infertility (inability to 
have children) in women 
and men 
• low platelet count 
(mild) with 
increased risk of 
bleeding 
• darkening of nail beds 
• acne 
• tiredness 
• infection 
• fetal changes if you 
become pregnant 
while taking 
cyclophosphamide 
• heart problems with high doses, 
with chest pain, shortness of 
breath, swollen feet or rapid 
weight gain 
• severe allergic reactions 
• skin rash 
• scarring of bladder 
• kidney damage (renal tubular 
necrosis) which can lead to kidney 
failure 
• scarring of lung tissue, with cough 
and shortness of breath 
• second cancer, which can happen 
years after taking this drug 
• death from infection, bleeding, heart 
failure, allergic reaction, or other 
causes 
Fludarabine 
Common 
Less Common 
Rare, but may be serious 
• low white blood cell 
(WBC) count with 
increased risk of 
infection 
• low platelet count with 
increased risk of 
bleeding 
• low red blood cell count 
(anemia) with tiredness 
and weakness 
• tiredness (fatigue) 
• nausea 
• vomiting 
• fever and chills 
• infection 
• pneumonia 
• diarrhea 
• loss of appetite 
• weakness 
• pain 
• numbness and tingling in hands and/or 
feet related to irritation of nerves 
• changes in vision 
• agitation 
• confusion 
• clumsiness 
• seizures 
• coma 
• cough 
• trouble breathing 
• intestinal bleeding 
• weakness 
• death due to effects on the brain, 
infection, bleeding, severe anemia, 
skin blistering, or other causes 
 
Prescribing Information for Cyclophosphamide: 
https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/212501s000lbl.pdf 
 


 
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Prescribing Information for Fludarabine: 
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020038s032lbl.pdfRisks 
associated with pre-medications 
 
Acetaminophen 
Risks associated with acetaminophen are rare but can include possible low WBC count, low 
RBC count, low PLT count and skin rash. Acetaminophen can also cause liver injury if more 
than the prescribed dose is taken. Subjects should not exceed the maximum total daily dose of 
4 g/day and should avoid consuming alcohol when taking acetaminophen.  
Prescribing Information for Acetaminophen: 
https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/204767s000lbl.pdfAcyclovir 
The most common side effects observed in individuals receiving acyclovir PO are low RBC 
count, low WBC count and malaise. There are reports of worsening in subjects with a history 
of renal disease, however, this has been reported for higher doses than the 400 mg of 
acyclovir received in this study. 
Prescribing Information for Acyclovir: 
https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/018828s030,020089s019,019909
s020lbl.pdfAllopurinol 
The most common risks associated with allopurinol are increased risk of gout and skin rash 
which may sometimes be severe. Other common risks include diarrhea, nausea, alkaline 
phosphatase increase, increase in liver enzymes, possible low WBC count, low RBC count, 
and low platelet count. Rarely patients experience renal dysfunction. The risks of developing 
gout and possible renal dysfunction can be reduced by ensuring sufficient fluid intake to 
maintain a balanced daily urine output (2 liters). 
Prescribing Information for Allopurinol: 
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/016084s044lbl.pdfDiphenhyd
ramine 
The most common side effects observed in individuals receiving diphenhydramine are 
sedation, sleepiness, dizziness, disturbed coordination, pain in the middle of the upper 
abdomen and thick secretions from the respiratory tract. 
Prescribing Information for Diphenhydramine: 
https://www.accessdata.fda.gov/drugsatfda docs/label/2013/091526lbl.pdf 


 
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APPENDIX F. THE COMMON TERMINOLOGY CRITERIA FOR 
ADVERSE EVENTS (CTCAE)  VERSION 5.0 
 
https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/ctcae_v5_quick_refere
nce_5x7.pdf 
 


 
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APPENDIX G. INSTRUCTIONS FOR DILUTION AND 
ADMINISTRATION OF IL-2 
For the purposes of this study, subcutaneous (SC) IL-2 6 million units will be given every other 
day for a total of 3 doses beginning after the NK cell infusion. Dose for patients weighing less 
than 45 kg: 3 million units/m2 
 
A vial containing 22 million International Units (mIU)  of Proleukin should be reconstituted with 
1.2 ml of sterile water as follows:  
Using sterilised injection syringe and injection needle, inject 1.2 ml sterile water into the vial of 
Proleukin. Direct the diluent against the side of the vial to avoid excessive foaming. Swirl gently 
to facilitate complete dissolution of the powder. Do not shake.  
Following reconstitution, the concentration of the obtained solution is 18mIU/ml. Withdraw 0.33 
ml (containing 6 mIU of Proleukin) with a sterile injection syringe and inject subcutaneously. 
Reconstituted or diluted Proleukin is stable for up to 48 hours at refrigerated and room 
temperatures, 2° to 25°C (36° to 77°F). However, since this product contains no preservative, the 
reconstituted and diluted solutions should be stored in the refrigerator (from the Product Label).