Conditions: NHL Non Hodgkin Lymphoma Diffuse Large B Cell Lymphoma High-grade B-cell Lymphoma
Keywords: auto HSCT Stem cell transplantation Lymphoma
Allocation: NON_RANDOMIZED | Intervention model: SEQUENTIAL
Enrollment: 7
Healthy volunteers: no

Brief summary:
This is a Phase I multi-center study to evaluate the safety of FT596 when given with rituximab as relapse prevention in patients who have undergone an autologous hematopoietic stem cell transplant (auto-HSCT) for diffuse large or high-grade B cell lymphoma.

Detailed description:
This study uses a single dose of the investigational product FT596 in the early post-transplant period. Rituximab or an FDA approved by biosimilar including Rituxan®, Truxima®, and Ruxience™ is given 48 to 72 hours prior to FT596. The goal of this study is to 1) establish a maximum tolerated dose (MTD) of FT596 when given 30 days after transplant and 2) to confirm the MTD and safety of giving a single dose of FT596 at Day 7 post-transplant starting at one dose level below the MTD identified at Day 30.

Arms:
arm 1: Up to three sequential FT596 dose levels are planned for Day 30 administration: (Dose Level 1: 9x10\^7 cells/dose, Dose Level 2: 3x10\^8 cells/dose, Dose Level 3: 9x10\^8 cells/dose with a Dose Level -1: 3x10\^7 cells/dose tested only if dose limiting toxicity events (DLT) occur at dose level 1).The maximum tolerated dose will be determined by using a modified continual reassessment method (CRM). arm 2: Up to three sequential FT596 dose levels are planned for Day 30 administration: (Dose Level 1: 9x10\^7 cells/dose, Dose Level 2: 3x10\^8 cells/dose, Dose Level 3: 9x10\^8 cells/dose with a Dose Level -1: 3x10\^7 cells/dose tested only if dose limiting toxicity events (DLT) occur at dose level 1).The maximum tolerated dose will be determined by using a modified continual reassessment method (CRM). arm 3: Up to three sequential FT596 dose levels are planned for Day 30 administration: (Dose Level 1: 9x10\^7 cells/dose, Dose Level 2: 3x10\^8 cells/dose, Dose Level 3: 9x10\^8 cells/dose with a Dose Level -1: 3x10\^7 cells/dose tested only if dose limiting toxicity events (DLT) occur at dose level 1).The maximum tolerated dose will be determined by using a modified continual reassessment method (CRM).

Interventions: intervention 1: FT596 intervention 2: Rituximab
Intervention descriptions: intervention 1: FT596 is given 2-3 days after rituximab; however, it may be delayed for up to 7 days until all rituximab infusion related toxicities resolve to ≤Grade 1. intervention 2: Rituximab 375 mg/m\^2 is administered as an IV infusion per institutional standard of care and package insert on 2-3 days (48 to 72 hours) prior to the FT596 infusion

Protocol document:
Prot_SAP_000.pdf: 
Masonic Cancer Center, University of Minnesota 
Cancer Experimental Therapeutics Initiative (CETI) 
 
 
FATE FT596 with Rituximab as Relapse Prevention in High Risk 
Patients after Autologous Hematopoietic Stem Cell Transplantation 
for Non-Hodgkin Lymphoma  
CPRC #2019LS230 
MT2019-46 
IND #19675 
 
 
University of Minnesota 
Principal Investigator/IND Sponsor 
Veronika Bachanova, MD, PhD 
 
Co-Principal Investigators: 
Daniel Weisdorf, MD (University of Minnesota) 
Todd A. Fehniger, MD, PhD (Washington University) 
 
Co-Investigators (UMN): 
Claudio G. Brunstein, MD, PhD 
Joseph Maakaron, MD 
Murali Janakiram, MD, MS 
Najla El Jurdi, MD 
 
 
Collaborators: 
Jeffrey S. Miller, MD* 
David H. McKenna, Jr., MD* 
*Will not consent patients to enroll on study 
 
 
Biostatistician: 
Todd E DeFor, MS 
University of Minnesota 
 
Version Date: 
November 30, 2020 
 
 
Confidential 


CPRC # 2019LS230 (MT2019-46) – FT596 plus Rituximab as Post Auto-HSCT Relapse Prophylaxis 
 
 
 
 
 
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Key Study Personnel Contact Information 
Contact Information 
Role 
Veronika Bachanova, MD, PhD 
Division of Hematology/Oncology/Transplantation 
Medicine Hematology Office 
MMC 480  
420 Delaware Street SE 
Minneapolis, MN 55455 
Phone: 612-625-5469 
Email: bach0173@umn.edu 
Study PI/IND Sponsor 
Julianne Feola, PhD 
Masonic Cancer Center Clinical Trials Office 
925 Delaware St. SE 
Suite 310 Dinnaken MC 2131 
Minneapolis, MN. 55414 
Phone: 612 626-5174 
Email: affilates@umn.edu  
Fax: 612-625-6468 
Multisite Program 
Manager 
 
Refer to the Procedures Manual for Participating Sites for a complete list of study personnel and 
contact information.  
 
 


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Revision History 
 
Revision 
# 
Version Date 
Revision Details 
Consent 
Revision 
 
Mar 13, 2020 
Original to FDA 
n/a 
 
Apr 08, 2020 
In response to FDA IR April 6 2020 
n/a 
 
Apr 09, 2020 
am 
In response to FDA IR April 8 2020 
Additional edits: 
 Revise Section 8 – Tests and procedures to reflect more 
frequent follow-up and increased research related sample 
collection 
 Edits through-out to reflect a single dose of rituximab and a 
single dose of FT596 
n/a 
 
Apr 09, 2020 
pm 
In response to the FDR IR April 9 2020 – original version to 
CPRC 
 
 
 
May 20, 2020 
CCPM and general edits before IRB submission: 
 Synopsis, Section 3, Section 8, Section12.1: make consistent 
throughout protocol that rituximab is given 2-3 days prior to 
FT596, clarify only on dose of FT596 is given in this study 
 Schema, Synopsis, Section 6.4, Section 10.4, Section 12.4: 
revise monitoring for excessive toxicity (stopping rules) is from 
day of transplant not day of FT596. 
 Schema, Section 3, Sections 6.2 and 6.3, Section 8 and other 
places: add a +/- 1 day window for Day 7 and Day 30 FT596 
infusion to permit some flexibility of scheduling for individual 
patients  
 Section 6.1.2 – update FT596 administration language to be 
consistent without other Fate protocols 
 Section 7.2 Schema, Section 8.1 – add a Day 21 timepoint for 
disease reassessment, vascular access assessment, etc. for 
Component 1 to permit rituximab administration on Day 28 for 
Day 30 FT596. 
 Section 7.2 – add recommended IV hydration to reduce the risk 
of DMSO related toxicity 
 Section 7.3 – add monitoring of CRP and ferritin 3 times per 
week until resolution in the event CRS is diagnosed (with 
caveat missed testing will not be a deviation as patients maybe 
outpatient)- 
 Section 8.1 – remove KPS row, add row for concomitant 
medications, vascular access assessment, testing associated 
with CRS and neurotoxicity  
 Section 8.2 – refine research related samples and collection 
schedule 
 Section 10.7 – update expedited reporting table to reflect 
Advarra as IRB of record and other updates 
 Delete Appendix I as Karnofsky PS not assessed (not part of 
eligibility  
 Other minor edits and clarifications through-out (tracked) 
Initial 
consent 


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Revision 
# 
Version Date 
Revision Details 
Consent 
Revision 
1 
Oct 29 2020 
 Synopsis, schema, Sections 3-5, Section 8 - General update to 
permit study consent/registration and enrollment after HCT 
 Section 7.3 – clarify IL-6 sample collection and update Table 1 
tocilizumab administration guidelines for hypotension refractory 
to fluid boluses, add Actemra® (tocilizumab) prescribing info to 
References 
 Section 8.2 – add Day 28 CRP and ferritin, Add research 
samples at 3, 6, and 12 month post-transplant follow-up 
 Section 8,2 – delete the row for chimerisms from the research 
samples – update the 6 ml green top tubes with a new footnote 
1 with instructions to use part of the green tops for PK samples 
(replacing chimerisms as testing done at the institutional level 
would not provide meaningful results).  
 Section 8.2 – move PRA anti-HLA antibodies testing from prior to 
transplant to prior to FT596, add baseline safety samples for 
Fate 
 Section 4.3 – correct wording “no requirement” for systemic 
immunosuppression during FT596 treatment period 
 Delete Section 5.3 and move wording to Section 5.2 
 Minor edits to Section 8.1 removing unnecessary con med 
assessment time points and updating footnote 6 to match the 
schedule of vital sign monitoring to Section 6.1.2 
 Section 10.7 – Delete row in required reporting table for DLT 
and SR reporting to the SAE coordinator as now automatically 
receives notification via OnCore. 
 Other minor edits and clarifications 
Yes 
2 
Nov 30 2020 
 Synopsis, Section 6.1, Section 9.2 and throughout protocol 
clarify rituximab may be Rituxan or any FDA approved 
biosimilars 
 Synopsis, Schema, Section 6, Section 8 – permit a +3 day 
window from the targeted FT596 targeted administration (Day 30 
or Day 7 post-transplant) for the rituximab/FT596 “package”. 
Rituximab or an FDA approved biosimilar administration remains 
at 48-72 hours prior to the day of the planned FT596 infusion. 
 Other minor edits and clarifications 
yes 


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TABLE OF CONTENTS 
 
Key Study Personnel Contact Information ................................................................................ 2 
Key Abbreviations .................................................................................................................... 7 
Protocol Synopsis .................................................................................................................... 8 
Study Schema........................................................................................................................ 11 
1 
Objectives ....................................................................................................................... 13 
1.1 Primary Objective .................................................................................................... 13 
1.2 Secondary Objectives .............................................................................................. 13 
1.3 Correlative Objectives ............................................................................................. 13 
2 
Background and Significance .......................................................................................... 13 
2.1 Introduction and Rationale for the Approach ............................................................ 13 
2.2 Determination of Cohort With High Risk of Post-HSCT Relapse .............................. 14 
2.3 The Role of Rituximab Post-Transplant ................................................................... 15 
2.4 FT596 ...................................................................................................................... 16 
2.5 Study Rationale ....................................................................................................... 18 
3 
Study Design .................................................................................................................. 19 
4 
Patient Selection ............................................................................................................. 22 
4.1 Inclusion Criteria ...................................................................................................... 22 
4.2 Exclusion Criteria .................................................................................................... 22 
4.3 Confirmation of Continuing Eligibility Post-Transplant .............................................. 23 
5 
Patient Screening and Enrollment ................................................................................... 23 
5.1 Registration with the University of Minnesota Clinical Trials Office .......................... 23 
5.2 Patient Enrollment to Study Treatment in OnCore ................................................... 24 
5.3 Patients Who Do Not Begin Study Treatment .......................................................... 24 
6 
Treatment Plan ............................................................................................................... 25 
6.1 Rituximab or an FDA Approved Biosimilar and FT596 Administration General Guidelines
 
25 
6.2 Component 1: Identify FT596 MTD When Given on Day 30 Only ............................ 27 
6.3 Component 2: Safety of FT596 when given at Day 7 based on the MTD from Component 
1 
28 
6.4 Monitoring for Excessive Toxicity (Component 1 and Component 2) ....................... 29 
6.5 Permitted and Prohibited Concomitant Medications/Therapies ................................ 29 
6.6 Duration of Treatment .............................................................................................. 29 
6.7 Duration of Study Participation ................................................................................ 29 
6.8 Continuation of Follow-Up via a Separate Long-Term Follow-Up Protocol ............... 30 
7 
Management of Potential Toxicities Associated FT596 ................................................... 30 
7.1 Infusion Related Reaction Associated with FT596 ................................................... 31 
7.2 DMSO Related Risks ............................................................................................... 32 
7.3 Cytokine Release Syndrome (CRS) or CRS-Like Symptoms ................................... 32 
7.4 Neurotoxicity............................................................................................................ 34 
7.5 Tumor Lysis Syndrome (TLS) .................................................................................. 39 
7.6 Myelosuppression, Immunosuppression, Bone Marrow Failure, and Infections ....... 39 
8 
Schedule of Treatment, Tests, and Procedures .............................................................. 40 


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8.1 Required Clinical Care Evaluations ......................................................................... 41 
8.2 Research Related Tests and Procedures ................................................................ 43 
9 
Study Agents .................................................................................................................. 45 
9.1 FT596 ...................................................................................................................... 45 
9.2 Rituximab (Rituxan or an FDA approved biosimilar, e.g. Truxima and Ruxience) .... 45 
10 Adverse Event Monitoring, Documentation, and Reporting ............................................. 46 
10.1 Adverse Event Terminology ..................................................................................... 47 
10.2 AE Documentation Requirements ............................................................................ 48 
10.3 SAE Documentation and Reporting ......................................................................... 49 
10.4 Dose Limiting Toxicity and Excessive Toxicity (Stopping Rule Events) Documentation 
and Reporting Requirements ........................................................................................... 49 
10.5 Documentation of Death and Reporting Requirements ............................................ 50 
10.6 Institutional Event Reporting Table .......................................................................... 50 
10.7 Expedited MCC Reporting Requirements (MCC) ..................................................... 51 
11 Study Data Collection and Monitoring ............................................................................. 51 
11.1 Data Management ................................................................................................... 51 
11.2 Case Report Forms ................................................................................................. 52 
11.3 Data and Safety Monitoring Plan (DSMP) ................................................................ 52 
11.4 Participating Site Monitoring .................................................................................... 53 
11.5 Teleconferences – Lead Site and Participating Sites ............................................... 53 
11.6 Record Retention .................................................................................................... 54 
12 Statistical Considerations ................................................................................................ 54 
12.1 Study Designs ......................................................................................................... 54 
12.2 Sample Size ............................................................................................................ 56 
12.3 Statistical Analysis ................................................................................................... 57 
12.4 Monitoring Guidelines .............................................................................................. 57 
13 Conduct of the Study ...................................................................................................... 58 
13.1 Good Clinical Practice ............................................................................................. 58 
13.2 Ethical Considerations ............................................................................................. 58 
14 References ..................................................................................................................... 59 
Appendix I – LUGANO 2014 CLASSIFICATION: TUMOR RESPONSE ASSESSMENT IN 
LYMPHOMA .......................................................................................................................... 61 
 
 


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Key Abbreviations 
Abbreviation 
Definition 
ABW 
actual body weight 
ADL 
activities of daily living 
AE 
adverse event 
Auto-HSCT 
autologous hematopoietic stem cell transplant 
CAR 
chimeric antigen receptor 
CFR 
Code of Federal Regulations 
CNS 
central nervous system 
CRS 
cytokine release syndrome 
CTCAE 
Common Terminology Criteria for Adverse Events 
DLCO 
diffusing capacity of the lungs for carbon monoxide 
DLT 
Dose limiting toxicity 
eCRF 
electronic case report form 
EOT 
end of treatment 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
GvHD 
graft-versus-host disease 
HCT 
hematopoietic cell transplantation 
HSCT 
hematopoietic stem cell transplantation 
IB 
Investigator’s Brochure 
ICH 
International Conference on Harmonisation 
IL-15RF 
IL-15 receptor alpha fusion protein 
IND 
Investigational New Drug 
IPI 
International Prognostic Index 
IRB 
Institutional Review Board 
IV 
intravenous 
LTFU 
long-term follow-up 
NCI 
National Cancer Institute 
NHL 
non-Hodgkin lymphoma 
NK 
natural killer 
OS 
overall survival 
PBMC 
peripheral blood mononuclear cell 
PD 
progressive disease 
PFS 
progression free survival 
PFT 
pulmonary function test 
RECIST 
Response Evaluation Criteria in Solid Tumors 
rhIL-15 
Recombinant human interleukin-15 
SAE 
serious adverse event 
SD 
stable disease 
SOC 
standard of care 
SR 
stopping rule 
TITE-CRM 
time-to-event continual reassessment method 
TRM 
treatment related mortality 
ULN 
upper limit of normal 


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Protocol Synopsis 
FATE FT596 with Rituximab as Relapse Prevention in High Risk Patients after Autologous 
Hematopoietic Stem Cell Transplantation for Non-Hodgkin Lymphoma 
Study Design: 
This is a Phase I multi-center study to evaluate the safety of FT596 when given with rituximab as relapse 
prevention in patients who have undergone an autologous hematopoietic stem cell transplant (auto-
HSCT) for diffuse large or high-grade B cell lymphoma.  
 
For the majority of participants, this study is presented to the patient and consent is signed at the time 
consent for the autologous transplant is obtained. Research related samples are collected prior to the 
start of conditioning on any consented patient. Alternatively, a patient may be consented and enrolled 
after the transplant provided the patient can begin treatment within their assigned window.  
 
The transplant procedures and follow-up are conducted per institutional standard of care. Participation 
in this study does not affect or impact the transplant, supportive care, and subsequent post-transplant 
care, except that, if post-transplant radiation therapy is planned, it must be delayed until after Day 100. 
 
FT596 is comprised of allogeneic natural killer (NK) cells expressing a CD19-targeted chimeric antigen 
receptor (CAR), a high-affinity non cleavable CD16 receptor (hnCD16), and an interleukin (IL)-15/IL-15 
receptor alpha fusion protein (IL-15RF). FT596 is an off-the-shelf cellular product and expected to be 
uniform in composition. The mechanism of action is targeting B-cell tumor cells through direct 
cytotoxicity, CAR-mediated targeting of CD19 as well as through antibody-dependent cellular 
cytotoxicity (ADCC) in combination with rituximab for a dual-targeting approach.  
 
This study uses a single dose of the investigational product FT596 in the early post-transplant period. 
Rituximab or an FDA approved by biosimilar including Rituxan®, Truxima®, and Ruxience™ is given 2-
3 days prior to FT596. The goal of this study is to 1) establish a maximum tolerated dose (MTD) of 
FT596 when given 30 days after transplant and 2) to confirm the MTD and safety of giving a single dose 
of FT596 at Day 7 post-transplant starting at one dose level below the MTD identified at Day 30.  
 
Component 1: Identify the maximum tolerated dose (MTD) of FT596 when given as a single dose 
at Day 30.  
Up to three FT596 dose levels are planned for Day 30 administration (with a +3 day window): (Dose 
Level 1: 9x107 cells/dose, Dose Level 2: 3x108 cells/dose, Dose Level 3: 9x108 cells/dose with a Dose 
Level -1: 3x107 cells/dose tested only if DLT at DL1).The maximum tolerated dose will be determined 
by using a modified continual reassessment method (CRM).  
 
Patients are enrolled in cohorts of 3 starting at Dose Level 1. A minimum of 28 days will separate each 
cohort. For Dose Level 1 a minimum of 28 days will separate each patient to assess for dose limiting 
toxicity (DLT). In subsequent cohorts, the 1st and 2nd patient will be separated by at least 28 days and 
at least 14 days will separate the 2nd and 3rd patient.  
 
Each new cohort of three patients will be sequentially assigned to the most appropriate dose based on 
the updated toxicity probabilities under the continuous reassessment method (CRM), and the MTD will 
be identified when the total sample size of 18 is exhausted or 6 patients are sequentially enrolled at the 
same dose. 
 
Dose limiting toxicity is defined as any of the following events within 28 days of FT596 dosing based on 
CTCAE v5: 
 Grade 4 hematologic toxicity lasting > 7 days (not including lymphopenia)  
 Grade 4 non-hematologic toxicity  
 Grade ≥3 FT596 Infusion Related Reaction 
 Grade 2 acute GVHD that requires steroid therapy >7 days or progression after 3 days of steroids 
or has partial response after 14 days of treatment 
 Grade ≥3 acute GVHD 
 Grade 4 cytokine release syndrome (CRS) 
 Grade 3 CRS that does not resolve to < Grade 2 in 72 hours 


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 Grade 3 neurotoxicity 
 Grade 3 organ toxicity involving vital organs; cardiac, central nervous system and pulmonary which 
lasts longer than 7 days including Grade 3 Investigations (laboratory values) of any duration that 
indicate damage to vital organs.  
 Any Grade 3 non-hematological toxicity that does not resolve to ≤Grade 2 within 72 hours; 
excepting Grade 3 renal and hepatic toxicity which may take up to 7 days to resolve to ≤Grade 2 
 
Note: Once enrollment is completed for Component 1, enrollment will be suspended. A summary for 
Component 1, including safety data (summary of DLT and SR events) will be provided to the FDA for 
review. Only after receiving their permission will Component 2 begin enrollment. If permission is not 
received, the study will end. 
  
Component 2: To determine the safety of FT596 when given at Day 7 based on the MTD from
Component 1.   
Component 2 will use a similar design but identifies the MTD of FT596 when given as a single dose at 
Day 7 (with a +3 day window) post-transplant. Up to two dose levels of FT596 are planned (one dose 
level below the MTD from Component 1 and the MTD from Component 1). Any two sequential dose 
levels of FT596 may be included: Dose Level -1: 3x107 cells/dose, Dose Level 1: 9x107 cells/dose, Dose 
Level 2: 3x108 cells/dose, Dose Level 3: 9x108 cells/dose.  
 
The maximum tolerated dose will be determined by using a modified continual reassessment method 
(CRM). Patients are enrolled in cohorts of 3 starting at one dose level below the MTD of Component 1 
(MTD-1). Only the MTD-1 and the MTD of Component 1 will be tested. A minimum of 28 days will 
separate each cohort. For the 1st cohort a minimum of 28 days will separate each patient to assess for 
dose limiting toxicity (DLT). In subsequent cohorts, the 1st and 2nd patient will be separated by at least 
28 days and at least 14 days will separate the 2nd and 3rd patient. Each new cohort of three patients will 
be sequentially assigned to the most appropriate dose based on the updated toxicity probabilities. The 
MTD will be identified when the total sample size of 18 is exhausted or 6 patients are sequentially 
enrolled at the same dose. 
 
The DLT events for Component 2 are the same as in Component 1 except for the addition of: 
• Non-engraftment by Day 28 post-transplant 
 
Monitoring guidelines for excessive toxicity (Stopping Rule events) Component 1 and 
Component 2 (ONLY POST FT596 EVENTS COUNT HERE)) 
The following events occurring after the FT596 infusion are measures of excessive toxicity based on 
Day 0 as the Transplant Day). Each component is monitored separately. 
 Mortality by Day 100  
 Grade III-IV Acute GVHD by Day 100  
 Any Grade 4 FT596 Infusion Related Reaction 
 Any Grade 4 Dose Limiting Toxicity (DLT) event 
 Grade 4 Lymphopenia (<200 cells/uL) at Day 100  
 Engraftment failure by Day 28 (Component 2 only)  
 
Study 
Products: 
FT596 and rituximab (Rituxan or any FDA approved biosimilar) 
Primary 
Objective: 
The primary objective of this study is: 
Component 1: Establish a maximum tolerated dose (MTD) of FT596 when given 30 days after 
transplant.  
Component 2: Confirm the MTD and the safety of giving a single dose of FT596 at Day 7 post-transplant 
using one dose level below the MTD (MTD -1) or the MTD from Component 1. 
 


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Secondary 
Objectives: 
 To evaluate the adverse events related to FT596 administered post auto-HSCT in combination with 
rituximab (Rituxan or an FDA approved biosimilar, e.g. Truxima and Ruxience).  
 To determine preliminary efficacy based on progression free survival (PFS) and relapse/progression 
at 12 months post auto-HSCT. 
 To determine the incidence of non-relapse mortality at 100 days and 1 year post auto-HSCT. 
 
Correlative 
Objectives: 
Correlative objectives include: 
 To evaluate persistence of FT596 in blood after each FT596 infusion by immunophenotyping and 
PCR up to 1 year. 
 To assess the association of FT596 cell persistence with safety and anti-tumor activity. 
 To assess the association of baseline clinical and tumor characteristics with safety and response 
endpoints following administration of FT596. 
 
Key Inclusion 
Criteria: 
(at time of 
consent/ 
screening) 
 Diagnosis of diffuse large B cell lymphoma or aggressive (high-grade) B-cell lymphoma for which an 
autologous stem cell transplant is planned or recently completed 
 High risk for relapse defined as at least one of the below: 
o 
Primary induction failure (no complete or partial remission at any point after diagnosis) 
o 
Initial remission duration < 12 months 
o 
Lack of complete metabolic (PET scan) response after 2-3 cycles of salvage chemotherapy 
o 
Evidence of c-myc and bcl-2 and/or bcl-6 re-arrangement (double hit or triple hit lymphoma)  
o 
Age-adjusted International prognosis index (IPI) 2-3 at relapse  
 Age 18 years or older at the time of signing consent. 
 Agrees to use adequate contraception (or evidence of sterility) at least 12 months after the last dose 
of rituximab. 
 Agrees and signs the separate consent for up to 15 years of follow-up (Long-term Follow-up study 
CPRC#2020LS052)  
 Provides voluntary written consent prior to the performance of any research related activities. 
 
Key Exclusion 
Criteria: 
(at time of 
consent/ 
screening) 
 Receipt of any investigational therapy within 28 days prior to the first dose of FT596 or planned use 
of an investigational therapy during the first 100 days after transplant 
 Planned post-transplant irradiation prior to Day +100 
 Seropositive for HIV, active Hepatitis B or C infection with detectable viral load by PCR 
 Body weight <50kg 
 Known allergy to the following FT596 components: albumin (human) or DMSO 
 Unable to receive rituximab 
 
Post-HCT 
Eligibility 
Confirmation 
 No life-threatening medical issues (i.e. ongoing Grade 4 adverse events) where, in the opinion of the 
treating investigator, use of FT596 is not in the patient’s best interest.  
 No active uncontrolled infection. 
 Adequate organ function post-transplant including: 
 
alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤5 x ULN (Grade 2 
CTCAE v5) 
 
total bilirubin ≤1.5 x ULN (Grade 1 CTCAE v5) 
 
serum creatinine ≤1.5 x ULN (Grade 1 CTCAE v5) 
 
oxygen saturation ≥93% on room air 
 For Day 30 dosing only – CBC requirement consistent with engraftment (ANC>500, platelet>20,000 
without transfusion support within previous 7 days). There are no CBC parameters for Day 7 dosing. 
 
Enrollment 
Plan: 
Component 1: a maximum of 18 patients, but most likely 12 if toxicity is as expected 
Component 2:  a maximum of 18 patients, but most likely 12 if toxicity is as expected 
 
Accrual: 
It is expected 12-18 patients could be enrolled per year with two sites. 
 


Study Schema 
Treatment may be given as an inpatient or outpatient – there is no study driven requirement for a hospital admission. 
 
Component 1 - FT596 at Day 30 Post Transplant to Identify MTD 
 
Consent*       
     HSCT                            dz eval  XI       
Pre-HSCT period 
 
   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Transplant Day 
         0 
 
+7       +21       +30        
 +60                + 100                +180            +365          
* Alternatively consent/initial screening may be done after HSCT – refer to Section 5. 
Schedule for disease assessment around Day +21 to allow for rituximab to be given on Day 28 
 I    FT596 at assigned dose* Note a +3 day window is permitted for FT596 dosing (i.e. Day +31, Day +32 or Day +33) 
X   Rituximab (Rituxan or an FDA approved biosimilar, e.g. Truxima and Ruxience) 375 mg/m2 IV 2-3 days before 
FT596 (refer to Section 6.1 for details) 
 
*Dose Levels for Identification of MTD 
Dose Level  
FT596 Cells per Dose Enrollment Plan 
-1 
3 x 107 cells 
Tested only if Dose Level 1 has DLT 
1 (start) 
9 x 107 cells 
Enroll 3 patients at Dose Level 1 with at least 28 days between each of the 3 
patients. Once the 28 day DLT assessment periods ends for all 3 patients, 
enroll the next cohort of 3 patients to the most appropriate dose based on the 
updated toxicity probabilities. A minimum of 28 days must separate the 1st and 
2nd patients and a minimum of 14 days must separate the 2nd and 3rd patient 
within a cohort. The MTD is identified when the total sample size of 18 is 
exhausted or 6 patients are sequentially enrolled at the same dose.  
2 
3 x 108 cells 
3 
9 x 108 cells 
 
Component 1 dose limiting toxicity is defined as any of the following events within 28 days after FT596 
dosing based on CTCAE v5: 
 Grade 4 hematologic toxicity lasting > 7 days (not including lymphopenia)  
 Grade 4 non-hematologic toxicity  
 Grade ≥3 FT596 Infusion Related Reaction 
 Grade 2 acute GVHD that requires steroid therapy >7 days or progression after 3 days of steroids or 
has partial response after 14 days of treatment 
 Grade ≥3 acute GVHD 
 Grade 4 cytokine release syndrome (CRS) 
 Grade 3 CRS that does not resolve to < Grade 2 in 72 hours 
 Grade 3 neurotoxicity 
 Grade 3 organ toxicity involving vital organs; cardiac, central nervous system and pulmonary that lasts 
longer than 7 days including Grade 3 Investigations (laboratory values) of any duration that indicate 
damage to vital organs.  
 Any Grade 3 non-hematological toxicity that does not resolve to ≤Grade 2 within 72 hours; excepting 
Grade 3 renal and hepatic toxicity which may take up to 7 days to resolve to ≤Grade 2 
 
Component 1 monitoring guidelines for excessive toxicity (Stopping Rule events) occurring after 
the FT596 infusion based on Day 0 as the Transplant Day (ONLY POST FT596 EVENTS COUNT 
HERE): 
 Mortality by Day 100 
 Grade III-IV Acute GVHD by Day 100  
 Any Grade 4 FT596 Infusion Related Reaction 
 Any Grade 4 Dose Limiting Toxicity (DLT) event  
 Grade 4 Lymphopenia (<200 cells/uL) at Day 100  
 


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NOTE: Component 2 may not begin until after the FDA gives permission to proceed (refer to Section 6.3) 
Component 2 - Safety of FT596 when given at Day 7 based on the MTD from Component 1 
 
 
Consent*       
     HSCT                 XI       
Pre-HSCT period 
 
   
 
 
 
 
 
 
 
 
 
 
 
 
 
Transplant Day 
         0 
 
+7      
       +30        
 +60                + 100                +180            +365          
* Alternatively consent/initial screening may occur after HSCT – refer to Section 5 
 
 
    
 I    FT596 at assigned dose* Note a +3 day window is permitted for FT596 dosing (i.e. Day +8, Day +9 or Day +10) 
 X   Rituximab (Rituxan or an FDA approved biosimilar, e.g. Truxima and Ruxience) 375 mg/m2 IV 2-3 days before 
FT596 (refer to Section 6.1 for details)  
 
*Dose Levels for Identification of MTD at Day 7 
Dose Level based on MTD 
from Component 1 
Enrollment Plan 
MTD – 1 Dose Level (Start) 
Enroll 3 patients at Dose Level 1 with at least 28 days between each of the 3 
patients. Once the 28 day DLT assessment periods ends for all 3 patients, 
enroll the next cohort of 3 patients to the most appropriate dose based on the 
updated toxicity probabilities. A minimum of 28 days must separate the 1st and 
2nd patients and a minimum of 14 days must separate the 2nd and 3rd patient 
within a cohort. The MTD is identified when the total sample size of 18 is 
exhausted or 6 patients are sequentially enrolled at the same dose.   
MTD 
 
Component 2 dose limiting toxicity is defined as any of the following events within 28 days after FT596 
dosing based on CTCAE v5: 
 Grade 4 hematologic toxicity lasting > 7 days (not including lymphopenia)  
 Grade 4 non-hematologic toxicity  
 Grade ≥3 FT596 Infusion Related Reaction 
 Grade 2 acute GVHD that requires steroid therapy >7 days or progression after 3 days of steroids or has 
partial response after 14 days of treatment 
 Grade ≥3 acute GVHD 
 Grade 4 cytokine release syndrome (CRS) 
 Grade 3 CRS that does not resolve to < Grade 2 in 72 hours 
 Grade 3 neurotoxicity 
 Grade 3 organ toxicity involving vital organs; cardiac, central nervous system and pulmonary that lasts 
longer than 7 days including Grade 3 Investigations (laboratory values) of any duration that indicate 
damage to vital organs.  
 Any Grade 3 non-hematological toxicity that does not resolve to ≤Grade 2 within 72 hours; excepting 
Grade 3 renal and hepatic toxicity which may take up to 7 days to resolve to ≤Grade 2 
 Non-engraftment by Day 28 post-transplant 
 
Component 2 monitoring guidelines for excessive toxicity (Stopping Rule events) occurring after 
the FT596 infusion based on Day 0 as the Transplant Day (ONLY POST FT596 EVENTS COUNT 
HERE): 
 
Mortality by Day 100  
 
Grade III-IV Acute GVHD by Day 100  
 
Any Grade 4 FT596 Infusion Related Reaction 
 
Any Grade 4 Dose Limiting Toxicity (DLT) event 
 
Grade 4 Lymphopenia (<200 cells/uL) at Day 100  
 
Engraftment failure by Day 28 (Component 2 only) 
 
 


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1 
Objectives 
1.1 Primary Objective 
The primary objective of this study is: 
Component 1: Establish a maximum tolerated dose (MTD) of FT596 when given 
30 days after transplant and  
Component 2: Confirm the MTD and safety of giving a single dose of FT596 at 
Day 7 post-transplant using one dose level below the MTD (MTD -1) or the MTD 
from Component 1. 
1.2 Secondary Objectives 
 To evaluate the adverse events related to FT596 administered post auto-HSCT 
in combination with rituximab (Rituxan or an FDA approved biosimilar, e.g. 
Truxima and Ruxience).  
 To determine preliminary efficacy based on progression free survival (PFS) and 
relapse/progression at 12 months post auto-HSCT. 
 To determine the incidence of non-relapse mortality at 100 days and 1 year post 
auto-HSCT. 
1.3 Correlative Objectives 
Correlative/exploratory objective include: 
 To evaluate persistence of FT596 in blood after each FT596 infusion by 
immunophenotyping and PCR up to 1 year. 
 To assess the association of FT596 cell persistence with safety and anti-tumor 
activity. 
 To assess the association of baseline clinical and tumor characteristics with 
safety and response endpoints following administration of FT596. 
 
 
2 
Background and Significance 
2.1 Introduction and Rationale for the Approach  
Non-Hodgkin lymphoma (NHL) is the second most common hematologic 
malignancy. Diffuse large B cell lymphoma (DLBCL), the most common NHL 
subtype (30-40%), is an aggressive cancer that is rapidly fatal unless promptly 
treated. In the US, approximately 440,000 patients were treated for NHL in 2010 
(SEER.gov). Although most patients initially achieve a remission, treatment fails 
for about 50% of patients. For these patient, Parma trial established the use of 
high-dose therapy (such as BEAM; BCNU, Etoposide, Cytarabine and Melphalan) 
with auto-HSCT as the standard of care. (Kondo 2016) 
 


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However relapse occurs frequently and estimated 5-year PFS rate is 
approximately 50-60%. (Vose 2013, Lerner 2007, Gisselbrecht 2012, Cuccuini 
2012)  Prospective trial compared Rituximab (R) BEAM vs 131I-tositumomab BEAM 
to demonstrate similar PFS 48.6% (95% CI 38-58%) vs 47.9% (95% CI, 38.2% to 
57%) at 2 years after auto-HSCT.  Large multicenter CORAL study reported similar 
PFS of 52%. (Gisselbrecht 2012) Almost all relapses occur before 12 months post-
HSCT. (Vose 2013, Lerner 2007, Gisselbrecht 2012, Hamadani 2014) 
2.2 Determination of Cohort With High Risk of Post-HSCT Relapse  
1. Lack of CR after front-line therapy and high International Prognostic 
Index (IPI) Score. 
In the R-BEAM prospective trial, the only significant covariate in the multivariate 
model for PFS was disease status at the time of auto-HSCT. (Vose 2013) The 
patients in CR at auto-HSCT had an improved PFS compared with patients with a 
chemotherapy-sensitive persistent or relapsed lymphoma not in CR (HR 1.63; 
95%CI 1.14-2.33). CORAL trial compared two salvage chemotherapy regimen in 
DLBCL and assessed the role of rituximab maintenance after auto-HSCT. Two 
factors associated with worse PFS were early relapse after front-line 
chemotherapy of < 12 months, and a secondary age-adjusted International 
Prognostic Index (IPI) score of 2-3. (Lerner 2007) 
 
Center for International Blood and Marrow Transplantation Registry (CIBMTR) 
investigators recently analyzed outcomes after auto-HSCT and noted that patients 
with early failure (defined as primary induction failure and relapse <12 months from 
diagnoses) experienced relapse/progression rate of 47% (95% 41% to 52%) and 
PFS of 44% (95% CI, 38% to 50%) with 2-fold higher failure rate (P < .001) within 
first 9 months post auto-HSCT compared to patients with late treatment failure. 
(Hamadani 2014) 
 
Data from our center demonstrated the 
median PFS of 2 months versus 8 
months post auto-HSCT for the high- 
and low-risk IPI groups (total 80 
patients). These findings support using 
the IPI assessed at relapse as a 
selection criterium to select patients 
who are treated with autologous 
transplantation for DLBCL in second 
complete 
or 
partial 
remissions. 
(Figure 1) (Lerner 2007). 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Figure 1. Progression free survival in DLCBL after autologous 
transplant in low and high risk groups defined by International 
Prognostic Index (IPI) at relapse 


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2. Alterations of c-myc gene is associated with poor PFS. 
Approximately 
5-10% 
of 
DLBCL 
harbor 
a 
8q24/MYC 
rearrangement 
(MYC(+)). WHO now categorize this disease as aggressive B-cell lymphoma with 
MYC and BCL2 and/or BCL6 rearrangements. CORAL study reported outcomes 
of 28 patients with MYC(+) rearrangement, targeted as either simple hit (25%) or 
complex hits (75%) including MYC/BCL2, MYC/BCL6, and MYC/BCL2/BCL6. 
(Cuccuini 2012) Compared to the MYC(-) DLBCL patients, the MYC(+) DLBCL 
patients presented with a more elevated LDH level and more advanced age 
adjusted IPI (P = .0039). The 4-year PFS in the MYC(+) DLBCL was 18%.  
 
Another recent multicenter retrospective study examined the 331 DLBCL patients 
with primary induction failure in rituximab era defined as primary induction failure 
or relapse < 6 months from end of therapy. (Costa 2017) The presence of PIF, 
intermediate-high/high NCCN-IPI or MYC translocation predicted 2-year OS of 
13.6% constituting ultra-high risk features. Our 132 patients who underwent 
autoHCT 2-year OS was 74.3%, 59.6% and 10.7% for patients with 0,1 and 2-3 
ultra-high risk features respectively.  
2.3 The Role of Rituximab Post-Transplant 
Rituximab’s key anti-cancer mechanism of action is mediated through FcγRIII 
(CD16) on NK cells; this receptor is by far the most potent NK activating receptor. 
Rituximab crosslinks CD16 and triggers vigorous production of cytokines and 
FT596 cell degranulation, leading to target cell killing (a process referred to as 
antibody-dependent cellular cytotoxicity; ADCC). Targeting CD20 on lymphoma 
cells with rituximab dramatically improves initial remission rates (by 10-20%), but 
resistance is common. The international CORAL study tested the impact of 
maintenance rituximab after autografting by evaluating DLBCL patients treated 
with rituximab or controls. (Gisselbrecht 2012) The 4-year event-free survival 
rates were identical in the two groups (52% and 53%). The limitations of rituximab 
efficacy may be due to decreased CD16 expression or poor NK cell function post 
transplantation. We hypothesize that FT596 engineering will enhance rituximab 
activity post-HCT. 


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CD16 expression is decreased after treatment with rituximab in vivo. In a 
control experiment (Figure 2 top panel), we incubated CD56dim NK cells with 
rituximab (10 μg/ml) in vitro and 
showed that it does not block 
CD16 binding. We then tested 
peripheral blood from patients 
with DLBCL before and after the 
therapy 
with 
rituximab 
(375mg/m2 x 4 doses). At 
baseline 
CD56dim 
NK 
cells 
expressed high levels of CD16. 
After rituximab therapy, a large 
proportion of blood NK cells 
(46%) downregulated CD16 and 
became CD16 negative (Figure 
2, 
lower 
panel 
16.4% 
vs 
46.2%)) demonstrating that rituximab treatment doses clip CD16 off NK cells in 
vivo. 
 
The cellular product FT596 is rationally engineered to express a high-affinity 
non-cleavable CD16 receptor (hnCD16) to engage rituximab and mediate killing of 
DLBCL tumor cells which survived BEAM chemotherapy.  
2.4 FT596  
FT596 is an allogeneic NK cell immunotherapy produced from a clonal master 
human-induced pluripotent stem cell (iPSC) line engineered to express the 
following: a) a CD19-targeted CAR; b) a high-affinity non-cleavable CD16 receptor 
(hnCD16); and c) an IL-15/IL-15 receptor alpha fusion protein (IL-15RF) 
(Jing 2015; Li 2018). The clonal master cell bank (MCB) used for the production of 
FT596 was generated by selecting and expanding a single, well-characterized 
iPSC clone with defined transgene copy number and integration sites. The use of 
a clonal MCB as the starting material for routine Current Good Manufacturing 
Practices (cGMP) production of FT596 is intended to directly address many of the 
limitations associated with current patient- and donor-specific cell CD19-targeted 
CAR therapies.  
Notably, many doses of FT596 drug product can be uniformly produced in a single 
manufacturing campaign. These doses of drug product are homogeneous and can 
be (i) tested to assure compliance with a pre-defined quality specification, 
(ii) cryopreserved in an infusion media, and (iii) stored to maintain a sustainable 
inventory. As such, in the clinical setting, FT596 has off-the-shelf availability for 
Prior to Rituximab                      After Rituximab
Peripheral blood             In vitro control
CD56dim NK cells         CD56dim NK cells 
Rituximab in 
vitro 10μg/ml
Prior to Rituximab                      After Rituximab
Peripheral blood             In vitro control
CD56dim NK cells         CD56dim NK cells 
Rituximab in 
vitro 10μg/ml


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potential use in multi-dose regimens in broad treatment populations, which may 
prove critical for driving long-term durable responses in patients with progressing 
disease. 
The engineered features of FT596 are designed to result in greater potency and 
specificity against transformed B cells, and therefore, the potency of FT596 is 
expected to be superior to that of patients’ endogenous NK cells. These features 
justify its investigation in B-cell malignancies: 
 The cytotoxic effector function of FT596 is expected to be superior to that of 
patients’ endogenous NK cells, which are diminished in number and poorly 
functional due to prior treatment regimens (e.g., chemotherapy) and disease-
related immunosuppression. 
 FT596 expresses a CD19-targeted CAR that has been specifically developed 
to support NK cell anti-tumor efficacy against CD19+ cells. Unlike CARs 
developed for T cells that include, for example, a CD28 co-stimulatory domain, 
FT596 CAR-mediated targeting is driven by NKG2D transmembrane and 2B4 
co-stimulatory domains, which supports potent killing against CD19+ B cells. In 
nonclinical studies, CAR designs consisting of NKG2D transmembrane and 
2B4 co-stimulatory domains outperformed a conventional CAR, consisting of 
CD28 and 41BB co-stimulatory domains, when expressed in NK cells (Li 2018). 
 FT596 includes the expression of hnCD16 which consists of naturally occurring 
158V polymorphism and an additional genetic alteration (S179P) that prevents 
cleavage of CD16. In clinical studies in patients whose endogenous NK cells 
express the high-affinity CD16 Fc receptor 158V variant, higher objective 
response rates (ORRs) and increased progression free-survival (PFS) were 
observed with treatment with rituximab, cetuximab, and trastuzumab (Cartron 
2002; Bibeau 2009; Musolino 2008). In addition, the genetic alteration S179P 
prevents downregulation of CD16 upon activation due to cleavage of CD16 by 
the metalloproteinase ADAM17 (Jing 2015; Lajoie 2014), a mechanism that 
regulates NK cell activity (Romee 2013). Nonclinical studies conducted with 
cryopreserved FT596-R, the non-GMP research-use equivalent of FT596, 
demonstrated that the combination of FT596-R with the US Food and Drug 
Administration (FDA)-approved antibody-dependent cellular cytotoxicity 
(ADCC)-inducing monoclonal antibodies (mAbs), specifically rituximab, 
resulted in enhanced anti-tumor activity as compared to mAb alone, peripheral 
blood NK cells alone, or FT596 alone. Specifically, FT596-R in combination 
with rituximab demonstrated improved targeting of CD19+ CD20+ cancer cells, 
enhanced cytokine production, and enhanced combinatorial activity with 
chimeric antigen receptor targeting CD19 antigen. Based on these 


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observations, FT596 will be initially investigated in combination with the 
monoclonal ADCC-inducing antibodies targeting CD20, rituximab, and 
obinutuzumab, which are approved for the treatment of B-cell malignancies, 
and where CD19 loss or modification as a mechanism of resistance supports 
the targeting against a second tumor antigen expressed by the tumor B cells. 
 FT596 expresses IL-15RF designed to provide an endogenous activation 
and proliferation signal, obviating the need for exogenous cytokine 
administration such as IL-2 and IL-15, which have been associated with 
significant toxicities that may limit clinical usage when incorporated into 
clinical studies of peripheral blood NK cells (Cooley 2019). 
 Nonclinical evaluation of umbilical cord blood-derived NK cells engineered 
to express a CD19 CAR and secrete IL-15 demonstrated the feasibility of the 
overall approach of providing engineered NK cells for the treatment of B-cell 
malignancies, with clinical trials being planned (Liu 2018). 
Overall, FT596 is expected to be uniform in composition, well-tolerated, available 
off-the-shelf for potential use in multi-dose treatment cycles, and to have improved 
anti-tumor activity through direct cytotoxicity, CAR-mediated targeting of CD19, as 
well as through ADCC in combination with mAbs for a unique dual-targeting 
approach. These features provide the rationale for the proposed Phase I study of 
a single dose of FT596 in combination with rituximab as relapse prophylaxis after 
an auto-HSCT for the treatment of aggressive B-cell and DBLCL lymphoma. If 
found safe, the next step will be to propose up to 3 doses of FT596 administered 
at Day 7, Day 30, and Day 60 post-transplant. 
2.5 Study Rationale 
There is an urgent need to develop well-tolerated and effective therapies to sustain 
remission in DLBCL post auto-HSCT.  
 
Our hypothesis is that the FT596 will eliminate the chemotherapy resistant residual 
lymphoma cells which persist after high dose chemotherapy. The rationale to use 
FT596 post autoHCT is to harness the immune mediated anti-tumor killing at the 
time of minimal disease burden which is achieved by using high dose chemotherapy 
BEAM.  
 
The rationale to initiate FT596 dose escalation portion at Day 30 is to allow patient 
recovery from toxicities of auto-HSCT and achieve stable blood count recovery. 
This timing is supported by our internal data which showed that median day of 
absolute neutrophil count (ANC) and platelet recovery occurred on days 10 and 19 


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after auto-HSCT. (Fair 2017) Day 30 is chosen to establish MTD and FT596 toxicity 
profile in transplant setting.  
 
The rationale to move the FT596 infusion closer to Day 0 is to harness the 
lymphodepleting effect of BEAM chemotherapy. BEAM produce lymphopenia and 
endogenous release of IL-15 at the levels comparable to low dose 
fludarabine/cyclophosphamide. (Shi 2008, Porrata 2010) The presence of 
immunologic (homeostatic) environment post-HSCT was determined by elevated 
blood levels of IL-15 around day 7-10 post-transplant. (Shi 2008) In addition, BEAM 
chemotherapy triggered surge of IL-15 (blood levels at day 15:  median 76.5pg/dl 
(range 5.4-219.2 pg/dl). (Porrata 2010) State of lymphopenia and endogenous 
cytokine surge early post-auto-HSCT may potentiate FT596 persistence in blood 
and in vivo expansion. 
 
The rationale to combine FT596 with CD20 targeting monoclonal antibody rituximab 
is to mediate dual targeting of CD20 and CD19 to avoid antigen escape and 
increase anti-tumor efficacy. The treatment goal is to eliminate chemoresistant 
lymphoma cells after autoHCT and improve 1-year PFS from 50% to 75%.  
 
3 
Study Design 
This is a Phase I multi-center study to evaluate the safety of a single dose of FT596 
when given with rituximab as relapse prevention in patients who have undergone 
an autologous hematopoietic stem cell transplant (auto-HSCT) for diffuse large or 
high-grade B cell lymphoma.  
 
This study is presented to the patient and consent is signed at the time consent for 
the autologous transplant is obtained. Research related samples are collected prior 
to the start of conditioning on any consented patient. Alternatively, a patient also 
may be consented, screened, and enrolled after the transplant provided the patient 
can begin treatment within the assigned window. 
 
The transplant procedures and follow-up are conducted per institutional standard 
of care. Participation in this study does not affect or impact the transplant, 
supportive care, and subsequent post-transplant care, except that, if post-
transplant radiation therapy is planned, it must be delayed until after Day 100. 
 
FT596 is comprised of allogeneic natural killer (NK) cells expressing a CD19-
targeted chimeric antigen receptor (CAR), a high-affinity non cleavable CD16 
receptor (hnCD16), and an interleukin (IL)-15/IL-15 receptor alpha fusion protein 
(IL-15RF). FT596 is expected to be uniform in composition, available off the shelf 


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for use in a multi dose treatment plan. The mechanism of action is targeting B-cell 
tumor cells through direct cytotoxicity, CAR-mediated targeting of CD19 as well as 
through antibody-dependent cellular cytotoxicity (ADCC) in combination with 
rituximab for a dual-targeting approach.  
 
This study uses a single dose of the investigational product FT596 in the early post-
transplant period. Rituximab (Rituxan or an FDA approved biosimilar, e.g. Truxima 
and Ruxience) is given 48 to 72 hours prior to FT596. The goal of this study is to 1) 
establish a maximum tolerated dose (MTD) of FT596 when given 30 days after 
transplant and 2) to confirm the MTD and safety of giving a single dose of FT596 at 
Day 7 post-transplant starting at one dose level below the MTD identified at Day 30.  
 
Component 1: Identify the maximum tolerated dose (MTD) of FT596 when given 
as a single dose at Day 30.  
 
Up to three FT596 dose levels are planned for administration on Day 30: Dose Level 
1: 9x107 cells/dose, Dose Level 2: 3x108 cells/dose, Dose Level 3: 9x108 cells/dose 
with a Dose Level -1: 3x107 cells/dose tested only if DLT at DL1.The maximum 
tolerated dose will be determined by using a modified continual reassessment 
method (CRM).  
 
Patients are enrolled in cohorts of 3 starting at Dose Level 1. A minimum of 28 days 
will separate each cohort. For Dose Level 1 a minimum of 28 days will separate 
each patient to assess for dose limiting toxicity (DLT). In subsequent cohorts, the 
1st and 2nd patient will be separated by at least 28 days and at least 14 days will 
separate the 2nd and 3rd patient.  
 
Each new cohort of three patients will be sequentially assigned to the most 
appropriate dose based on the updated toxicity probabilities under the continuous 
reassessment method (CRM), and the MTD will be identified when the total sample 
size of 18 is exhausted or 6 patients are sequentially enrolled at the same dose. 
 
Definitions of dose limiting toxicity and monitoring for excessive toxicity are found 
in Section 12.4.  
 
 
 


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Component 2: To determine the safety of FT596 when given at Day 7 based on 
the MTD from Component 1.   
 
NOTE: Component 2 may not begin until after the FDA gives permission to 
proceed (refer to Section 6.3). 
 
Component 2 will use a similar design but identifies the MTD of FT596 when given 
as a single dose at Day 7  post-transplant. Up to two dose levels of FT596 are 
planned (one dose level below the MTD from Component 1 and the MTD from 
Component 1). Any two sequential dose levels of FT596 may be included: Dose 
Level -1: 3x107 cells/dose, Dose Level 1: 9x107 cells/dose, Dose Level 2: 3x108 
cells/dose, Dose Level 3: 9x108 cells/dose. 
 
The maximum tolerated dose will be determined by using a modified continual 
reassessment method (CRM). Patients are enrolled in cohorts of 3 starting at one 
dose level below the MTD of Component 1 (MTD-1). Only the MTD-1 and the MTD 
of Component 1 will be tested. A minimum of 28 days will separate each cohort. 
For the 1st cohort a minimum of 28 days will separate each patient to assess for 
dose limiting toxicity (DLT). In subsequent cohorts, the 1st and 2nd patient will be 
separated by at least 28 days and at least 14 days will separate the 2nd and 3rd 
patient. Each new cohort of three patients will be sequentially assigned to the most 
appropriate dose based on the updated toxicity probabilities. The MTD will be 
identified when the total sample size of 18 is exhausted or 6 patients are 
sequentially enrolled at the same dose. 
 
Definitions of dose limiting toxicity and monitoring for excessive toxicity are found 
in Section 12. 4.  
 
Follow-up (all patients): Direct study participation ends at 1 year post-transplant.  
 
Long-Term Follow-Up (any patient who received at least one dose of FT596): 
After 1 year, follow-up will transfer to a separate long-term follow-up (LTFU) study 
(UMN CPRC #2020LS052) to continue the FDA’s required 15 year follow-up after 
treatment with a genetically modified cell therapy. Participation in the LTFU study 
is mandatory as part of the inclusion criteria of this treatment study. 
 
 
 
 


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4 
Patient Selection 
Study entry is open to adults 18 years and older regardless of gender, race or ethnic 
background. While there will be every effort to seek out and include females and 
minority patients, the patient population is expected to be no different than those adults 
undergoing an autologous transplant for non-Hodgkin lymphoma at the participating 
institutions.  
4.1 Inclusion Criteria  
 Diagnosis of diffuse large B cell lymphoma or aggressive (high grade) B-cell 
lymphoma for which an autologous stem cell transplant is planned or recently 
completed 
 High risk for relapse defined as at least one of the below: 
 
Primary induction failure (no complete or partial remission at any point after 
diagnosis 
 
Initial remission duration < 12 months 
 Lack of complete metabolic (PET scan) response after 2-3 cycles of salvage 
chemotherapy 
 Evidence of c-myc and bcl-2 and/or bcl-6 re-arrangement (double hit or triple 
hit lymphoma)  
 Age-adjusted International Prognostic Index (IPI) 2-3 at relapse  
 Age 18 years or older at the time of signing consent. 
 Agrees to use adequate contraception (or evidence of sterility) for at least 12 
months after the last dose of rituximab. 
 Agrees and signs the separate consent for up to 15 years of long-term follow-up 
study  
 Provide voluntary written consent prior to the performance of any research 
related activities. 
4.2 Exclusion Criteria  
• Receipt of any investigational therapy within 28 days prior to the first dose of 
FT596 or planned use of an investigational therapy during the first 100 days after 
transplant 
• Planned post-transplant irradiation prior to Day +100 
• Seropositive for HIV 
• Active Hepatitis B or C infection with detectable viral load by PCR 
• Body weight <50kg 
• Known allergy to the following FT596 components: albumin (human) or DMSO 
• Unable to receive rituximab 
 
 


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4.3 Confirmation of Continuing Eligibility Post-Transplant 
• No life-threatening medical issues (i.e. ongoing Grade 4 adverse events) where, 
in the opinion of the treating investigator, use of FT596 is not in the patient’s 
best interest.  
• No active uncontrolled infection 
• Adequate organ function post-transplant including: 
• 
alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤5 
x ULN (Grade 2 CTCAE v5) 
• 
total bilirubin ≤1.5 x ULN (Grade 1 CTCAE v5) 
• 
serum creatinine ≤1.5 x ULN (Grade 1 CTCAE v5) 
• 
oxygen saturation ≥93% on room air 
• For Day 30 dosing only – CBC requirement consistent with engraftment 
(ANC>500, platelet>20,000 without transfusion support within previous 7 days). 
There are no CBC parameters for Day 7 dosing. 
• No requirement for systemic immunosuppressive therapy (> 5mg prednisone 
daily) during the FT596 dosing period. 
 
FT596 may be delayed for up to 3 days for these events to resolve. 
 
 
5 
Patient Screening and Enrollment 
For the majority of participants, consent for this study will be presented as part of the 
pre-transplant discussion as research related samples are collected before beginning 
of conditioning chemotherapy.  
 
Alternatively, a patient also may be consented and enrolled after transplant provided 
the patient 1) can begin treatment within their assigned window, 2) they meet all of the 
inclusion criteria and none of the exclusion criteria based on the previously 
documented standard of care pre-transplant assessment and 3) meet the post-
transplant requirements found in Section 4.3. Research related procedures and 
sample collections missed due to late consenting are not protocol deviations. 
5.1 Registration with the University of Minnesota Clinical Trials Office 
Any patient who is consented is to be registered in OnCore by the site Study 
Coordinator or designee.  
 
If a patient is consented but is not enrolled in the study treatment (i.e. is found to 
be ineligible based on pre-transplant inclusion/exclusion criteria), the patient’s 
record is updated in OnCore as a screen failure and reason for exclusion recorded.  
 


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Additional information is found in the study’s Procedures Manual for Participating 
Sites. 
 
In addition, participating institutions are responsible for fulfilling any local study 
registration requirements. 
5.2 Patient Enrollment to Study Treatment in OnCore 
To be eligible for study treatment, the patient must sign the treatment consent and 
meet each inclusion criteria and none of the exclusion criteria on the eligibility 
checklist based on an eligibility assessment documented in the patient’s medical 
record. 
 
After transplant, the study doctor will need to assess the patient to determine if the 
criteria in Section 4.3 is met and continuing on the study is in the best interest of 
the patient based on their current medical situation.  
 
The patient is assigned to the currently enrolling treatment plan after the transplant 
and confirmation of continuing eligibility. 
5.3 Patients Who Do Not Begin Study Treatment 
If a patient is enrolled in the study (i.e. assigned a sequence number) and is later 
found unable to begin FT596, the patient will be removed from study and treated 
at the physician’s discretion. The study staff will update OnCore of the patient’s 
non-treatment status (off study) with the reason for removal from study prior to 
starting study treatment clearly indicated. The patient will be replaced to complete 
enrollment. Any data and research samples collected up to this point will be 
retained as detailed in the written consent document. 
 
If a patient receives FT596, they are considered on treatment and most continue 
follow-up per Section 8. 
 
 


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6 
Treatment Plan 
Primary supportive care is to continue according to the primary transplant protocol. 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.).  
 
Because they may inhibit NK cell function, systemic corticosteroids should be avoided 
during the treatment period (3 days before and through 14 days after FT596) unless 
absolutely required. Intravenous glucocorticoid as premedication for rituximab may be 
administered per the USPI or institutional guidelines. Methylprednisolone should be 
used as preferred glucocorticoid premedication given its shorter half-life.  
 
Treatment may be given as an inpatient or an outpatient. There is no protocol driven 
requirement for hospitalization. 
 
For scheduling purposes, the rituximab/FT596 “package” is administered with a +3 
day window from the targeted FT596 administration day (Day 30 or Day 7). Rituximab 
or an FDA approved biosimilar is given 2-3 days (48 to 72 hours) prior to the planned 
FT596 infusion. 
6.1 Rituximab or an FDA Approved Biosimilar and FT596 Administration 
General Guidelines 
Rituximab or an FDA approved biosimilar and FT596 are administered in the same 
manner regardless of FT596 dose and the administration days. Refer to the 
following sections for detailed information including enrollment plan, definition of 
dose limiting toxicity and early study stopping events.  
 Section 6.2 – Component 1: Identify FT596 MTD when given on Day 30 only. 
 Section 6.3 – Component 2: Determine the MTD and safety of Day 7 FT596. 
6.1.1 Rituximab or FDA Approved Biosimilar (2-3 days prior to each 
FT596 Administration) 
Rituximab (Rituxan or an FDA approved biosimilar, e.g. Truxima and Ruxience) 
375 mg/m2 is administered as an IV infusion per institutional practice and the 
specific product’s package insert on 2-3 days (48 to 72 hours) prior to the 
FT596. Pre-medications and supportive care per institutional standard of care 
guidelines. 
6.1.2 FT596 Administration 
FT596 is given 2-3 days after rituximab; however, it may be delayed for up to 
7 days until all rituximab infusion related toxicities resolve to ≤Grade 1. 
 


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FT596 Thawing Overview: FT596 is provided in one or more cryopreserved 
bags based on the patient’s dose level. The correct number of bags are 
transferred to the site of infusion using a validated cooler. Thawing occurs on 
the unit just prior to administration. When dose level requires multiple bags, 
bags are thawed sequentially. FT596 is stable for up to 60 minutes post-thaw. 
Administration of the cell product must begin within 60 minutes of thawing.  
FT596 Infusion guidelines: FT596 must be administered via gravity using a 
Fate approved IV administration set with an in-line filter. Total infusion time per 
bag is less than 10 minutes. If multiple bags are used, a short delay between 
infusions occur to allow for product thawing. To infusion 3 bags of cells (the 
maximum required for the dose levels in this study), total infusion time from the 
start of the 1st bag to the end of the last bag would be 30-40 minutes.  
Complete information is provided in the FT596 Storage, Handling, and 
Administration Guidance 
The end of administration time should be recorded after the rinse step has been 
completed. When the study drug administration has been completed, discard 
the empty study drug bag/tubing in accordance with local site policy. 
 
Pre-Medications: Prior to administration of FT596 and 4-6 hours later, patients 
should be pre-medicated with acetaminophen 650 mg orally (PO) and 
diphenhydramine 25 PO. Corticosteroids should not be used as pre-medication 
for FT596. 
 
Vital Signs: Vital signs (temperature, systolic and diastolic blood pressure, 
heart rate, and respiration rate) are performed in association with the FT596 
infusion at the following time points: within 15 minutes of the infusion start, at 
10 (±5) minutes during infusion, and every 15 (±5) minutes for 1 hour after the 
end of the last administered bag of FT596. 
 
Collection of research sample 30 (±5) minutes after the last bag of FT596 
is infused per Section 8.2. One or more bags are given depending on the dose 
level. 
 
Monitoring for Infusion Related Reactions: All patients are monitored for 
signs of an infusion related reaction. The highest grade infusion reaction for the 
FT596 infusion must be documented (and if applicable reported as a dose 
limiting toxicity and/or an SAE). 


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Refer to Section 7.1 for the management of any grade of an infusion related 
reaction. 
 
If a Grade 3 or 4 infusion related reaction occurs (defined as CTCAE v 5.0 – 
prolonged or life-threatening consequences), the infusion is stopped if possible 
(i.e. no additional bags of cells are given) and the patient receive supportive 
care per Section 7.1 guidelines. The patient will receive no further FT596.  
All patients are monitored for adverse events, dose limiting toxicity and death 
per Section 10.Refer to Section 7 for management of FT596 related toxicity. 
6.2 Component 1: Identify FT596 MTD When Given on Day 30 Only 
In Component 1, all patients will receive a single dose of FT596 on Day 30 (+3 
days) post-transplant. Rituximab (Rituxan or an FDA approved biosimilar, e.g. 
Truxima and Ruxience) 375 mg/m2 is administered 2-3 days prior to FT596. 
 
Up to three FT596 dose levels are planned: Dose Level 1: 9x107 cells/dose, Dose 
Level 2: 3x108 cells/dose, Dose Level 3: 9x108 cells/dose with a Dose Level -1: 
3x107 cells/dose tested only if DLT at DL1. Refer to Section 3 regarding the 
required staggering of enrollment. 
 
Dose limiting toxicity for Component 1 is defined as: 
Component 1 dose limiting toxicity is defined as any of the following events within 
28 days after the FT596 dosing based on CTCAE v5: 
 
Grade 4 hematologic toxicity lasting > 7 days (not including lymphopenia)  
 
Grade 4 non-hematologic toxicity  
 
Grade ≥3 FT596 Infusion Related Reaction 
 
Grade 2 acute GVHD that requires steroid therapy >7 days or progression 
after 3 days of steroids or has partial response after 14 days of treatment 
 
Grade ≥3 acute GVHD 
 
Grade 4 cytokine release syndrome (CRS) 
 
Grade 3 CRS that does not resolve to < Grade 2 in 72 hours 
 
Grade 3 neurotoxicity 
 
Grade 3 organ toxicity involving vital organs; cardiac, central nervous system 
and pulmonary that lasts longer than 7 days including Grade 3 Investigations 
(laboratory values) of any duration that indicate damage to vital organs.  
 
Any Grade 3 non-hematological toxicity that does not resolve to ≤Grade 2 
within 72 hours; excepting Grade 3 renal and hepatic toxicity which may take 
up to 7 days to resolve to ≤Grade 2 


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6.3 Component 2: Safety of FT596 when given at Day 7 based on the MTD from 
Component 1 
Prior to the start of enrollment in Component 2, a summary of patient data from 
Component 1 will be submitted to the FDA for their review. Included in this report 
will be enrollment and treatment information, a summary of adverse events, DLT’s 
SR events and SAEs as well as any disease status information. Component 2 may 
proceed if permission is received from the FDA. Otherwise the study will stop. 
In Component 2, all patients will receive a single dose of FT596 on Day 7 (+3 days) 
post-transplant. Rituximab (Rituxan or an FDA approved biosimilar, e.g. Truxima 
and Ruxience) 375 mg/m2 is administered 2-3 days prior to FT596. 
 
Up to two dose levels of FT596 are planned (one dose level below the MTD from 
Component 1 and the MTD from Component 1). Any two sequential dose levels of 
FT596 may be included: Dose Level -1: 3x107 cells/dose, Dose Level 1: 9x107 
cells/dose, Dose Level 2: 3x108 cells/dose, Dose Level 3: 9x108 cells/dose. Refer 
to Section 3 regarding the required staggering of enrollment. 
 
Dose limiting toxicity for Component 2 is defined as: 
Component 1 dose limiting toxicity is defined any of the following events within 28 
days after the FT596 dosing based on CTCAE v5: 
 
Grade 4 hematologic toxicity lasting > 7 days (not including lymphopenia)  
 
Grade 4 non-hematologic toxicity  
 
Grade ≥3 FT596 Infusion Related Reaction 
 
Grade 2 acute GVHD that requires steroid therapy >7 days or progression 
after 3 days of steroids or has partial response after 14 days of treatment 
 
Grade ≥3 acute GVHD 
 
Grade 4 cytokine release syndrome (CRS) 
 
Grade 3 CRS that does not resolve to < Grade 2 in 72 hours 
 
Grade 3 neurotoxicity 
 
Grade 3 organ toxicity involving vital organs; cardiac, central nervous system 
and pulmonary that lasts longer than 7 days including Grade 3 Investigations 
(laboratory values) of any duration that indicate damage to vital organs.  
 
Any Grade 3 non-hematological toxicity that does not resolve to ≤Grade 2 
within 72 hours; excepting Grade 3 renal and hepatic toxicity which may take 
up to 7 days to resolve to ≤Grade 2 
 
Non-engraftment by Day 28 post-transplant 


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6.4 Monitoring for Excessive Toxicity (Component 1 and Component 2) 
Each component will be monitored independently for the following events of 
excessive toxicity occurring after the FT596 infusion based on Day 0 as the 
Transplant Day (ONLY POST FT596 EVENTS COUNT HERE) per Section 12.4 
 Mortality by Day 100  
 Grade III-IV Acute GVHD by Day 100  
 Any Grade 4 FT596 Infusion Related Reaction 
 Any Grade 4 Dose Limiting Toxicity (DLT) event 
 Grade 4 Lymphopenia (<200 cells/uL) at Day 100  
 Engraftment failure by Day 28 (Component 2 only) 
6.5 Permitted and Prohibited Concomitant Medications/Therapies 
Primary supportive care is to continue according to the primary transplant protocol. 
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.).  
 
Because they may inhibit NK cell function, systemic corticosteroids should be 
avoided during the treatment period (3 days before the first FT596 through 14 days 
after) unless absolutely required. Intravenous glucocorticoid as premedication for 
rituximab may be administered per the USPI or institutional guidelines. 
Methylprednisolone should be used as preferred glucocorticoid premedication 
given its shorter half-life.  
 
Glucocorticoids should not be used as premedication for FT596. 
6.6 Duration of Treatment 
Treatment consists of a single dose of rituximab or an FDA approved biosimilar 
followed 2-3 days later by FT596 at the patient’s assigned dose/schedule. If a 
patient cannot receive FT596 by 7 days after rituximab due to unresolved infusion 
related toxicity (refer to Section 6.1), FT596 is not given. 
 
All patients receiving at least one dose of FT596 will be followed per Section 8.1. 
6.7 Duration of Study Participation 
Follow-up for disease and survival endpoints continues through 1 year post-
transplant.  
 
Direct study participation ends approximately 30 days after the last FT596 infusion 
and once an End of Treatment visit has occurred.  


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Clinical information including disease status and potential late toxicities associated 
with FT596 will be abstracted from follow-up visits associated with the transplant 
at Day 100, Day 180, Day 270 (if done), and Day 365. After Day 365 (1 year), the 
patient’s follow-up will transfer to a designated long-term follow-up protocol per 
Section 6.8. 
 
Rituximab or the FDA approved biosimilar may continue (independent of this 
study) per institutional practice. 
6.8 Continuation of Follow-Up via a Separate Long-Term Follow-Up Protocol 
FT596 is an engineered cellular immunotherapy product and the long-term safety 
risk is not known and may include conditions with delayed onset relative to FT596 
administration. Specific conditions potentially related to engineered cellular 
immunotherapy products such as FT596, including but not limited to, new 
malignancies, new or worsening neurologic disorders, new or worsening 
autoimmune or rheumatologic disorder, or new hematologic disorder will be 
documented and reported to the FDA as part of IND the annual report. 
 
At the end of the follow-up period for this study, follow-up for up to 15 years from 
the first FT596 cell infusion will continue on a separate long-term follow-up (LTFU) 
study (UMN CPRC#2020LS052). Consent to the LTFU study is obtained at the 
time of consent for the treatment study.  
7 
Management of Potential Toxicities Associated FT596 
No FT596 clinical data are available.  
 
The long-term safety risk is not known and may include conditions with delayed 
onset relative to FT596 administration. 
 
The information provided below is extrapolated from other NK cell products and 
other cell products in general. 
 
All adverse events will be defined and graded using the Common Terminology 
Criteria 
for 
Adverse 
Events 
(CTCAE) 
Version 
5.0 
https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/CTCAE_
v5_Quick_Reference_5x7.pdf 


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7.1 Infusion Related Reaction Associated with FT596 
Patients will be observed for the occurrence of acute allergic/anaphylactoid 
infusion reactions such as rigors and chills, rash, urticaria, hypotension, dyspnea, 
and angioedema during and after the infusion.  
 
The management of acute infusion or allergic reactions that occur during FT596 
administration is described below. 
If Grade 4 Infusion-Related Reaction (Life-threatening consequences; 
urgent intervention indicated): 
Stop FT596 administration. Do not restart. 
The volume of FT596 administered prior to the infusion-related reaction must be 
documented; retain any remaining product and contact Dr. Bachanova or designee 
for further instructions.  
If Grade ≤3 Infusion-Related Reaction (e.g., not rapidly responsive to 
symptomatic medication and/or brief interruption of infusion); recurrence of 
symptoms following initial improvement; hospitalization indicated for clinical 
sequelae): 
 Interrupt FT596 administration. 
 Manage symptoms, e.g., with antihistamines, antipyretics and analgesics, 
according to standard institutional practice standards. 
 Resume FT596 administration only upon complete resolution of the infusion-
related reaction and at the discretion of the Investigator. Given that FT596 
administration may involve single or multiple bags depending on the total 
planned dose and accounting for the stability of FT596 post-thaw, FT596 
administration may continue following resolution to a Grade 1 infusion-related 
reactions as follows: 
If single-bag FT596 dosing: 
 No additional FT596 may be administered. 
 The volume of FT596 administered prior to the infusion-related reaction must 
be documented; retain any remaining product and contact the Study PI (or 
designee) for further instruction. 
 Additional bags may not be administered to make up for FT596 that was not 
administered from the bag during which the infusion-related reaction 
occurred. 
 
 


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If multiple-bag FT596 dosing: 
 The volume of FT596 administered from the bag during which the infusion-
related reaction occurred must be documented; retain any remaining product 
from the bag and contact the Sponsor for further instruction. 
 If dosing with additional FT596 bags was planned, they may be thawed and 
administered. 
 Additional bags beyond what was originally planned may not be 
administered to make up for FT596 that was not administered from the bag 
during which the infusion-related reaction occurred. 
7.2 DMSO Related Risks 
FT596 is formulated in DMSO to enable cryopreservation. DMSO side effects and 
symptoms are generally associated with histamine release and include coughing, 
flushing, rash, chest tightness and wheezing, nausea and vomiting, and 
cardiovascular instability. Treat by slowing the rate of infusion, medicating with 
antihistamines, and treating symptoms per institutional practice. Recommended 
patients receive IV hydration with normal saline (NS) 250 ml bolus before and 250 
ml bolus after FT596 administration to reduce the potential risks associated with 
DMSO. 
7.3 Cytokine Release Syndrome (CRS) or CRS-Like Symptoms 
While CRS is a clearly defined syndrome with T-cell therapy, it is generally not 
believed to be a toxicity associated with NK cell therapies unless administered with 
cytokines that may independently drive the proliferation and activation of CD8+ T 
cells, e.g., exogenous IL-15 (Cooley 2019).  
 
If CRS is suspected, CRP and ferritin levels should be assessed locally, and a 
research related serum sample should be collected for an IL-6 level (if feasible). 
 
CRS must be graded as outlined in the ASTCT CRS consensus grading system 
per Section 10 (Lee 2019). 
 
If CRS occurs (e.g. a differential diagnosis is recorded in the institutional medical 
record), CRP and ferritin levels should be done three times weekly until the 
resolution of CRS per Section 8.1. In addition, a research related serum sample 
should be collected for an IL-6 level at the time of any change (increase or 
decrease) in the CRS grade. Because patients may be outpatients any missed 
collection time points will not be a protocol deviations. 
 
 


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Management of CRS should follow the recommended management algorithm 
provided in Table 1 (Neelapu 2018) and/or institutional practice. 
 
Table 1: Recommendations for the Management of Cytokine Release Syndrome 
Grade 
Sign/Symptom Management 
Grade 1 
Fever or 
organ toxicity 
 Acetaminophen and hypothermia blanket for the treatment of fever 
 Ibuprofen can be used as second treatment option for fever, if not 
contraindicated 
 Assess for infection using blood and urine cultures, and chest 
radiography 
 Empiric broad‑spectrum antibiotics and filgrastim if neutropenic 
 Maintenance IV fluids for hydration 
 Symptomatic management of constitutional symptoms and organ 
toxicities 
 Consider tocilizumab 8 mg/kg a IV or siltuximab 11 mg/kg IV for 
persistent (lasting ≥3 days) and refractory fever 
Grade 2 
Hypotension 
 IV fluid bolus of 500–1,000 mL of normal saline 
 Can give a second IV fluid bolus if systolic blood pressure remains 
<90 mmHg 
 Tocilizumab 8 mg/kg a IV or siltuximab 11 mg/kg IV for the treatment of 
hypotension that is refractory to fluid boluses; up to 3 additional doses 
of tocilizumab may be administered, and the interval between 
consecutive doses should be at least 8 hours. 
 If hypotension persists after two fluid boluses and anti‑IL‑6 therapy, start 
vasopressors, consider transfer to ICU, obtain echocardiogram, and 
initiate other methods of hemodynamic monitoring 
 In subjects at high-risk b or if hypotension persists after 1–2 doses of 
anti‑IL‑6 therapy, dexamethasone can be used at 10 mg IV every 6 
hours 
 Manage fever and constitutional symptoms as in Grade 1 
Hypoxia 
 Supplemental oxygen 
 Tocilizumab or siltuximab ± corticosteroids and supportive care, as 
recommended for the management of hypotension 
Organ 
toxicity 
 Symptomatic management of organ toxicities, as per standard 
guidelines 
 Tocilizumab or siltuximab ± corticosteroids and supportive care, as 
indicated for hypotension 
Grade 3 
Hypotension 
 IV fluid boluses as needed, as recommended for the treatment of 
Grade 2 CRS 
 Tocilizumab and siltuximab as recommended for Grade 2 CRS, if not 
administered previously 
 Vasopressors as needed 
 Transfer to ICU, obtain echocardiogram, and perform hemodynamic 
monitoring as in the management of Grade 2 CRS 
 Dexamethasone 10 mg IV every 6 hours; if refractory, increase to 20 mg 
IV every 6 hours 


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Table 1: Recommendations for the Management of Cytokine Release Syndrome 
Grade 
Sign/Symptom Management 
 Manage fever and constitutional symptoms as indicated for Grade 1 
CRS 
Hypoxia 
 Supplemental oxygen including high‑flow oxygen delivery and 
non‑invasive positive pressure ventilation 
 Tocilizumab or siltuximab plus corticosteroids and supportive care, as 
described above 
Organ 
toxicity 
 Symptomatic management of organ toxicities as per standard guidelines 
 Tocilizumab or siltuximab plus corticosteroids and supportive care, as 
described above 
Grade 4 
Hypotension 
 IV fluids, anti‑IL‑6 therapy, vasopressors, and hemodynamic monitoring 
as defined for the management of Grade 3 CRS 
 Methylprednisolone 1 g/day IV 
 Manage fever and constitutional symptoms as in Grade 1 CRS 
Hypoxia 
 Mechanical ventilation 
 Tocilizumab or siltuximab plus corticosteroids and supportive care, as 
described above 
Organ 
toxicity 
 Symptomatic management of organ toxicities as per standard guidelines 
 Tocilizumab or siltuximab plus corticosteroids and supportive care, as 
described above 
CRS, cytokine release syndrome; ICU, intensive care unit; IV, intravenous.  
NOTE: All medication doses indicated are for adults.  
a 
Maximum amount of tocilizumab per dose is 800 mg.  
b 
High-risk subjects include those with bulky disease and those with comorbidities. 
Reference: Neelapu 2018., Actemra USPI 
7.4 Neurotoxicity 
While CNS toxicity is a clearly defined syndrome associated with T-cell-based 
therapies, it is rare and generally not believed to be a toxicity associated with NK 
cell therapies. Neurotoxicity was reported in one trial of adoptively transferred NK 
cells given with subcutaneous IL-15 but the mechanism of the toxicity was not well 
defined (Cooley 2019). Nervous system toxicities following CD19 CAR-T therapy 
is characterized by encephalopathy, confusion, delirium, aphasia, obtundation, 
and seizures (Yescarta USPI 2017; Kymriah USPI 2018). Cases of cerebral edema 
have also been reported (Brudno 2016). 
If signs and symptoms of CNS toxicity occurs, it will be graded as outlined in the 
ASTCT consensus grading system for ICANS (Lee 2019, Section 10); management 
should follow current recommendations for CAR-T-cell therapies (Neelapu 2018). 
If the patient develops neurological toxicity for which cerebrospinal fluid (CSF) 
analysis is performed, in addition to standard clinical testing, the sample will be 
tested for Human Herpes Virus (HHV 6&7) since HHV6 and HHV-7 may cause 


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neurological toxicity in an immunocompromised host which may go unrecognized. 
In addition, quantitative testing in blood for HHV6 and HHV7 in the context of 
neurotoxicity will be done. Neurotoxicity must be monitored as per the Section 8.1 
using the ASTCT guidelines for grading ICANS (Section 10) based on the immune 
cell-associated encephalopathy (ICE) score. Determinants of the ICE score are 
outlined below. 
ICE Score Determination: 
 Orientation: Orientation to year, month, city, hospital: 1 point each for 
maximum of 4 points 
 Naming: Name 3 objects (e.g., point to clock, pen, button): 1 point each for 
maximum of 3 points 
 Following commands: (e.g., show me 2 fingers or close your eyes and stick 
out your tongue): 1 point 
 Writing: Ability to write a standard sentence (e.g., our national bird is the bald 
eagle): 1 point 
 Attention: Count backwards from 100 by ten: 1 point 
 
Table 2 ASTCT Immune Effector Cell-Associated Neurotoxicity Syndrome Grading a 
Neurotoxicity 
Domain  
Grade 1  
Grade 2  
Grade 3  
Grade 4  
ICE Score b  
7–9   
3–6  
0–2  
0 (subject is unarousable 
and unable to perform 
ICE.) 
Depressed level 
of 
consciousness c  
Awakens 
spontaneously 
Awakens to 
voice 
Awakens only to 
tactile stimulus 
Subjects is unarousable 
or requires vigorous or 
repetitive tactile stimuli to 
arouse. Stupor or coma. 
Seizure 
N/A 
N/A 
Any clinical seizure 
Focal/generalized that 
resolves rapidly; or 
Non-convulsive 
seizures on EEG that 
resolve with 
intervention 
Life-threatening 
prolonged seizure 
(>5 minutes); or 
Repetitive clinical or 
electrical seizures without 
return to baseline in 
between. 
Motor Findings d 
N/A 
N/A 
N/A 
Deep focal motor 
weakness such as 
hemiparesis or 
paraparesis 


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Table 2 ASTCT Immune Effector Cell-Associated Neurotoxicity Syndrome Grading a 
Neurotoxicity 
Domain  
Grade 1  
Grade 2  
Grade 3  
Grade 4  
Raised ICP/ 
Cerebral Edema 
N/A 
N/A 
Focal/local edema on 
neuroimaging e 
Diffuse cerebral edema 
on neuroimaging; 
Decerebrate or 
Decorticate posturing; or 
Cranial nerve VI palsy; or 
Papilledema; or 
Cushing's triad 
ASTCT, American Society for Transplantation and Cellular Therapy; CTCAE, Common Terminology Criteria for Adverse Events; 
ICANS, immune effector cell-associated neurotoxicity syndrome; ICE, immune effector cell-associated encephalopathy; ICP, 
intracranial pressure; EEG, electroencephalogram; N/A, not applicable. 
a 
ICANS grade is determined by the most severe event (ICE score, level of consciousness, seizure, motor findings, raised 
ICP/cerebral edema) not attributable to any other cause. For example, a subject with an ICE score of 3 who has a 
generalized seizure is classified as having Grade 3 ICANS. 
b 
A subject with an ICE score of 0 may be classified as having Grade 3 ICANS if the subject is awake with global aphasia. But 
a subject with an ICE score of 0 may be classified as having Grade 4 ICANS if the subject is unarousable.  
c 
Depressed level of consciousness should be attributable to no other cause (e.g. no sedating medication). 
d 
Tremors and myoclonus associated with immune effector cell therapies may be graded according to CTCAE v5.0 but they 
do not influence ICANS grading. 
e 
Intracranial hemorrhage with or without associated edema is not considered a neurotoxicity feature and is excluded from 
ICANS grading. It may be graded according to CTCAE v5.0. 
Reference: Lee 2019. 
Management of clinical neurotoxicity, i.e., encephalopathy syndrome, status epilepticus, 
and raised intracranial pressure, should follow current recommendations for CAR-T-cell 
therapies (Neelapu 2018; Table 3, Table 4, and Table 5) and/or institutional practice. 
  
Table 3 
Recommendations for the Management of Encephalopathy Syndrome 
Grade 
Management  
Grade 1 
 
 Vigilant supportive care; aspiration precautions; IV hydration  
 Withhold oral intake of food, medicines, and fluids, and assess swallowing  
 Convert all oral medications and/or nutrition to IV if swallowing is impaired  
 Avoid medications that cause central nervous system depression  
 Low doses of lorazepam (0.25–0.5 mg IV every 8 hours) or haloperidol (0.5 mg IV every 6 
hours) can be used, with careful monitoring, for agitated subjects  
 Neurology consultation  
 Fundoscopic exam to assess for papilloedema  
 MRI of the brain with and without contrast; diagnostic lumbar puncture with measurement of 
opening pressure; MRI spine if the subject has focal peripheral neurological deficits; CT scan 
of the brain can be performed if MRI of the brain is not feasible  
 Daily 30-minute EEG until toxicity symptoms resolve; if no seizures are detected on EEG, 
continue levetiracetam 750 mg every 12 hours  
 If EEG shows non-convulsive status epilepticus, treat as per algorithm in Table 4  
 Consider anti-IL-6 therapy with tocilizumab 8 mg/kg a IV or siltuximab 11 mg/kg IV, if 
encephalopathy is associated with concurrent CRS  
 
 
Grade 2 
 
 Supportive care and neurological work-up as described for grade 1 encephalopathy  
 Tocilizumab 8 mg/kg a IV or siltuximab 11 mg/kg IV if associated with concurrent CRS  
 Dexamethasone 10 mg IV every 6 hours or methylprednisolone 1 mg/kg IV every 12 hours if 
refractory to anti-IL-6 therapy, or for encephalopathy without concurrent CRS  


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Table 3 
Recommendations for the Management of Encephalopathy Syndrome 
Grade 
Management  
 Consider transferring subject to ICU if encephalopathy associated with Grade ≥2 CRS  
 
Grade 3 
 
 Supportive care and neurological work-up as indicated for Grade 1 encephalopathy 
 ICU transfer is recommended  
 Anti-IL-6 therapy if associated with concurrent CRS, as described for Grade 2 encephalopathy 
and if not administered previously  
 Corticosteroids as outlined for Grade 2 encephalopathy if symptoms worsen despite anti-IL-6 
therapy, or for encephalopathy without concurrent CRS; continue corticosteroids until 
improvement to Grade 1 encephalopathy and then taper  
 Stage 1 or 2 papilloedema with CSF opening pressure <20 mmHg should be treated as per 
algorithm presented in Table 4 
 Consider repeat neuroimaging (CT or MRI) every 2–3 days if subject has persistent grade ≥3 
encephalopathy 
Grade 4 
 
 Supportive care and neurological work-up as outlined for Grade 1 encephalopathy  
 ICU monitoring; consider mechanical ventilation for airway protection  
 Anti-IL-6 therapy and repeat neuroimaging as described for Grade 3 encephalopathy  
 High-dose corticosteroids continued until improvement to Grade 1 encephalopathy and then 
taper; for example, methylprednisolone IV 1 g/day for 3 days, followed by rapid taper at 250 
mg every 12 hours for 2 days, 125 mg every 12 hours for 2 days, and 60 mg every 12 hours 
for 2 days  
 For convulsive status epilepticus, treat as per algorithm in Table 4  
 Stage ≥3 papilloedema, with a CSF opening pressure ≥20 mmHg or cerebral oedema, should 
be treated as per algorithm in Table 4 
CAR, chimeric antigen receptor; CSF, cerebrospinal fluid; CRS, cytokine release syndrome; CT, computed tomography 
(scan); EEG, electroencephalogram; ICU, intensive care unit; IV, intravenous; MRI, magnetic resonance imaging. 
 a 
Maximum amount of tocilizumab per dose is 800 mg. 
Reference: Neelapu 2018. 
 
 
Table 4 Recommendations for the Management of Status Epilepticus 
Status Epilepticus 
Type 
Management 
Non-convulsive 
status epilepticus  
 
 Assess airway, breathing, and circulation; check blood glucose  
 Lorazepam a 0.5 mg IV, with additional 0.5 mg IV every 5 minutes, as 
needed, up to a total of 2 mg to control electrographical seizures  
 Levetiracetam 500 mg IV bolus, as well as maintenance doses  
 If seizures persist, transfer to ICU and treat with phenobarbital loading 
dose of 60 mg IV  
 Maintenance doses after resolution of non-convulsive status epilepticus 
are as follows: lorazepam 0.5 mg IV every 8 hours for three doses; 
levetiracetam 1,000 mg IV every 12 hours; phenobarbital 30 mg IV every 
12 hours  
Convulsive status 
epilepticus  
 
 Assess airway, breathing, and circulation; check blood glucose  
 Transfer to ICU  
 Lorazepam a 2 mg IV, with additional 2 mg IV to a total of 4 mg to control 
seizures  
 Levetiracetam 500 mg IV bolus, as well as maintenance doses  


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Table 4 Recommendations for the Management of Status Epilepticus 
Status Epilepticus 
Type 
Management 
 If seizures persist, add phenobarbital treatment at a loading dose of 
15 mg/kg IV  
 Maintenance doses after resolution of convulsive status epilepticus are: 
lorazepam 0.5 mg IV every 8 hours for three doses; levetiracetam 1,000 
mg IV every 12 hours; phenobarbital 1–3 mg/kg IV every 12 hours  
 Continuous electroencephalogram monitoring should be performed, if 
seizures are refractory to treatment  
ICU, intensive care unit; IV, intravenous. 
NOTE: All indicated doses of medication are for adult subjects.  
a 
Lorazepam is the recommended benzodiazepine because it is short-acting, compared with diazepam, and has been 
widely used in the management of seizures.  
Reference: Neelapu 2018. 
 
 
Table 5 Recommendation for the Management of Raised Intracranial Pressure (ICP) 
Stage 
Management 
Stage 1 or 2 papilledema a with CSF 
opening pressure of <20 mmHg without 
cerebral edema  
 Acetazolamide 1,000 mg IV, followed by 250–1,000 mg 
IV every 12 hours (adjust dose based on renal function 
and acid-base balance, monitored 1–2 times daily)  
Stage 3, 4, or 5 papilloedema, a with any 
sign of cerebral oedema on imaging 
studies, or a CSF opening pressure of  
≥20 mmHg  
 
 Use high-dose corticosteroids with methylprednisolone 
IV 1 g/day, as recommended for Grade 4 
encephalopathy syndrome (Table 3)  
 Elevate head end of the subject’s bed to an angle of 
30 degrees  
 Hyperventilation to achieve target partial pressure of 
arterial carbon dioxide (PaCO2) of 28–30 mmHg, but 
maintained for no longer than 24 hours  
 Hyperosmolar therapy with either mannitol (20 g/dL 
solution) or hypertonic saline (3% or 23.4%, as detailed 
below) 
 Mannitol: initial dose 0.5–1 g/kg; maintenance at  
0.25–1 g/kg every 6 hours while monitoring metabolic 
profile and serum osmolality every 6 hours, and 
withhold mannitol if serum osmolality is ≥320 
mOsm/kg, or the osmolality gap is ≥40  
 Hypertonic saline: initial 250 mL of 3% hypertonic 
saline; maintenance at 50–75 mL/h while monitoring 
electrolytes every 4 hours, and withhold infusion if 
serum Na levels reach ≥155 mEq/L  
 For subjects with imminent herniation: initial 30 mL of 
23.4% hypertonic saline; repeat after 15 minutes, if 
needed  
 If subject has ommaya reservoir, drain CSF to target 
opening pressure of <20 mmHg  
 Consider neurosurgery consultation and IV anesthetics 
for burst-suppression pattern on 
electroencephalography  


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Table 5 Recommendation for the Management of Raised Intracranial Pressure (ICP) 
Stage 
Management 
 Metabolic profiling every 6 hours and daily CT scan of 
head, with adjustments in usage of the aforementioned 
medications to prevent rebound cerebral edema, renal 
failure, electrolyte abnormalities, hypovolemia, and 
hypotension  
CSF, cerebrospinal fluid; CT, computed tomography (scan); IV, intravenous. 
NOTE: All medication doses indicated are for adults.  
a 
Papilledema grading should be performed according to the modified Frisén scale. 
Reference: Neelapu 2018. 
7.5 Tumor Lysis Syndrome (TLS) 
TLS is a possible risk associated with anti-tumor therapy however the risk of TLS 
on this protocol is exceedingly low because patients have received recent high-
dose chemotherapy and tumor bulk at time of autoHCT is low. TLS symptoms 
include nausea, vomiting, diarrhea, muscle cramps or twitches, weakness, 
numbness or tingling, fatigue, decreased urination, irregular heart rate, 
restlessness, irritability, delirium, hallucinations, and seizures. TLS is comprised of 
abnormal 
lab 
changes 
that 
include 
hyperuricemia, 
hyperkalemia, 
hyperphosphatemia, and hypocalcemia.  
Prophylaxis for and management of TLS should be done in accordance with 
standard institutional practice. 
7.6 Myelosuppression, Immunosuppression, Bone Marrow Failure, and 
Infections  
Therapies used for the treatment of hematologic malignancies have been reported 
to cause myelosuppression (neutropenia and/or thrombocytopenia), leukopenia, 
anemia; and in some cases, bone marrow failure. Hematologic cytopenias could 
be further compounded by other factors such as underlying disease, concurrent 
illnesses and concomitant medications.  
Close monitoring of complete blood count (CBC) and for the development of 
infections is strongly recommended. In general, management including transfusion 
support and use of growth factors, should be done in accordance with standard 
institutional practice.  
Non-engraftment  
We will collect detailed data on hematologic toxicity in Component 1 and will 
provide FDA with safety data for discussion before proceeding with Component 2 
if any Grade 4 hematologic toxicity occurs. Therefore, we will gain safety data on 
FT596 and expect that the risk of non-engraftment in Component 2 will be low. 
Non-engraftment by Day 28 will be confirmed by bone marrow biopsy (defined as 
<5% marrow cellularity). To mitigate the adverse outcome, all subjects in 


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Component 2 will undergo HLA typing and search for an allogeneic donor (related 
sibling, haplo-donor or unrelated donor) for potential rescue allogeneic donor 
hematopoietic cell transplantation. 
 
8 
Schedule of Treatment, Tests, and Procedures 
If a patient is consented after the transplant procedure, initial inclusion and exclusion 
criteria is abstracted for the standard of care assessment prior to transplant as 
permitted in the patient consent form document. No research related procedures or 
sample collections are permitted prior to consent signing.  
 
For scheduling purposes, the rituximab/FT596 “package” is administered with a +3 
day window from the targeted FT596 administration day (Day 30 or Day 7 post-
transplant). Rituximab or an FDA approved biosimilar is given 2 to 3 days (48 to 72 
hours) prior to the planned FT596 infusion. 
 
In the event of rituximab related toxicity, the FT596 infusion may delayed for up to 7 
days to permit resolution of any related adverse events to Grade 1 or better. 
 
A ± 1 Day window is permitted for visits through the End of Treatment (EOT) visit; 
however, whenever feasible do not shift subsequent time points off of the targeted day 
(based on the actual day of the FT596 infusion).  
 
After the EOT visit, follow-up for this study will coincide with the standard of care 
transplant follow-up schedule through 1 year post-transplant.  
 
In addition, targeted days may be altered as clinically appropriate. 


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8.1 Required Clinical Care Evaluations 
 
Screening 
prior to 
Transplant 
Post-Transplant 
Confirmation of 
Continuing Eligibility 
(approximately Day 21 
for Component 1) 
Day of Rituximab 
(Rituxan or an FDA 
approved 
biosimilar, e.g. 
Truxima and 
Ruxience) Infusion 
(-3 day window for 
labs and 
assessment) 
Day of 
FT596 
Infusion 
(Day 0^) 
Post FT596 Infusion (using Day 0 as the 
day of infusion) 
Abstract from 
patient’s EMR at 
each SOC visit 
until the 3 month 
post-transplant  
3, 6, and 12 
months from 
transplant at 
the time of 
SOC visit 
day 
2 
day 
7 
day 
14 
day 
21 
EOT visit 
day 28 
Consent 
X1 
 
 
 
 
 
 
 
 
 
 
Screening Assessment 
X 
 
 
 
 
 
 
 
 
 
 
Brief Medical Assessment 
 
 
 
X 
X 
X 
X 
X 
X 
 
 
Medical History 
X 
X 
 
 
 
 
 
 
 
 
X 
Concomitant Medications 
X 
 
 
X 
 
 
 
 
 
 
 
Assess Venous Access 
 
X 
 
 
 
 
 
 
 
 
 
Physical Exam 
X 
X 
X 
 
 
 
 
 
 
 
X 
ICANS (neurotoxicity) 
monitoring – refer to Section 
7.4 
 
X 
 
X 
 
X7 
X7 
X7 
X7 
 
X 
Weight 
X 
X 
X 
 
 
 
 
 
 
 
 
Height 
X 
 
 
 
 
 
 
 
 
 
 
Vitals and Pulse Oximetry 
X 
X 
X 
X 
 
 
 
 
X6 
 
 
Toxicity Assessment 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
CBC, diff, plt 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Basic metabolic panel (BMP)2  
 
 
X 
X 
X 
X 
X 
 
 
X 
Comprehensive metabolic 
panel (CMP) or equivalent3 
plus magnesium, phosporus 
X 
X 
X 
 
 
 
 
 
X 
X 
 
eGFR 
X 
X 
 
 
 
 
 
 
 
 
 
Urine or serum pregnancy 
test for WOCBP4 
X 
X 
 
 
 
 
 
 
 
 
 
If pt develops cytokine 
release syndrome (CRS): 
CRP, ferritin and, if testing 
available, IL-6  
 
 
 
If CRS is suspected obtain CRP, ferritin and IL-6 levels  
At diagnosis document CRP, ferritin and IL-6 levels 3 x weekly if inpt or at every 
outpt visit until resolution of CRS. Refer to Section 7.3. 
 
If pt develops neurotoxicity  
 
 
 
Refer to Section 7.4 for FDA recommended testing7  
 


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Screening 
prior to 
Transplant 
Post-Transplant 
Confirmation of 
Continuing Eligibility 
(approximately Day 21 
for Component 1) 
Day of Rituximab 
(Rituxan or an FDA 
approved 
biosimilar, e.g. 
Truxima and 
Ruxience) Infusion 
(-3 day window for 
labs and 
assessment) 
Day of 
FT596 
Infusion 
(Day 0^) 
Post FT596 Infusion (using Day 0 as the 
day of infusion) 
Abstract from 
patient’s EMR at 
each SOC visit 
until the 3 month 
post-transplant  
3, 6, and 12 
months from 
transplant at 
the time of 
SOC visit 
day 
2 
day 
7 
day 
14 
day 
21 
EOT visit 
day 28 
Disease staging 
X 
X 
 
 
 
 
 
 
 
 
Per SOC 
CXR or chest CT scan  
X 
 
 
 
 
 
 
 
 
 
 
PFTs5 
X 
 
 
 
 
 
 
 
 
 
 
EKG 
X 
 
 
 
 
 
 
 
 
 
 
^ day 0 is assigned to the day of the FT596 infusion regardless of whether the infusion is given Day 30 or Day 7 post-transplant   
 
1 
Consent is obtained prior to transplant – no re-consent required  
2 
basic metabolic panel consists of BUN, creatinine, calcium, glucose, lytes (CO2, Cl, Na, K)  
3 
comprehensive metabolic panel consists of albumin, alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), calcium, 
creatinine, glucose, lytes (CO2, Cl, Na,, K), total bilirubin, and total protein 
4 
women of child bearing potential 
5 
pulmonary function testing required only if symptomatic or prior known impairment 
6 
Vital signs (temperature, systolic and diastolic blood pressure, heart rate, and respiration rate) are performed in association with the FT596 infusion at the following time points: within 
15 minutes of the infusion start, at 10 (±5) minutes during infusion, and every 15 (±5) minutes for 1 hour after the end of the last administered bag of FT596. 
7 
If the patient develops neurological toxicity for which cerebrospinal fluid (CSF) analysis is performed, in addition to standard clinical testing, the sample should be tested for Human 
Herpes Virus (HHV 6&7) per Section 7.4. In addition, quantitative testing in blood for HHV6 and HHV7 in the context of neurotoxicity should be done. l 
8 
Long-term follow-up continues for up to 15 years per CPRC 2020LS052 
 
 
 


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8.2 Research Related Tests and Procedures 
 
Prior to start of 
pre-transplant 
chemo 
Post-
transplant/ 
pre-FT596 
Prior to 
Rituximab 
day 0^ 
Prior to 
FT596 
 
Post FT596 Infusion (using Day 0 as the day of infusion)  
3, 6, and 12 
months from 
transplant at 
time of SOC 
visit 
30 (± 5) 
minutes post 
infusion end 
day 
1 
day 
3 
day 
7 
day 
14 
day 
21 
End of treatment 
Visit  
day 28 
 
ferritin, CRP (to hospital lab 
charge to research) 
 
X 
 
 
 
 
 
 
 
 
X 
 
Assess for toxicity (including 
DLTs and SRs) per Section 
10 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Six 10 ml green top tubes1  
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
X (30 ml) 
One 10 ml of red top tube   
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
X (10 ml) 
One 10 ml green top tube1  
 
 
 
 
X 
 
 
 
 
 
 
 
Initial Safety samples:  
1 x 3 ml red top serum tube  
1 x 10 ml green top tube 
– store frozen in TTL and 
batch ship to Fate 
X 
X (only if 
consented 
after 
HSCT) 
 
 
 
 
 
 
 
 
 
 
Safety follow-up:  
1 x 3 ml red top serum tube  
1 x 10 ml green top tube 
1 x 6 ml yellow top tube 
 – store frozen in TTL and 
batch ship to Fate 
 
 
 
 
 
 
 
 
 
 
 
X 
PRA anti-HLA antibodies 
one 10 ml red top 
 
X  
 
 
 
 
 
 
 
 
X 
 
^ day 0 is assigned to the day of the FT596 infusion regardless of whether the infusion is given Day 30 or Day 7 post-transplant 
1- At TTL: PBMCs are isolated from the heparin/green tube at predetermined time points for PCR testing by Fate 
Refer to the Laboratory Manual for additional details


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If a patient is consented after HSCT, the 60 ml green tops and 10 ml red tops research 
related samples associated with the pre-transplant time point are not collected.  
 
All research samples go to the Masonic Cancer Center’s Translational Therapy Lab 
(TTL) except for the baseline and Day 28 for ferritin and CRP testing, and the PRA 
anti-HLA antibody samples done prior to study treatment start and at Day 28, which 
are charged to research but run in the treatment center’s clinical lab. If additional 
ferritin and/or CRP levels are collected as part of good medical care (i.e. development 
of signs of CRS) they are to be charged as standard of care. 
 
Note: If a patient is not abiding by the required clinical care calendar (Section 8.1), 
the collection schedule of research related samples may be altered or deleted or 
discontinued on an individual patient basis, as appropriate. During follow-up no visit 
will be solely for research and instead be linked with a standard of care visit closest to 
the targeted research related time point.  
 
It is recognized that with novel therapies as used in this study, the timing of protocol 
directed research samples may miss important patient specific events. For this 
reason, up to 3 extra samples for a total of 210 ml of blood may be collected at 
additional time points that are not specified above.  
 
Samples to evaluate lymphocyte number and phenotype will be collected as detailed 
above for the Masonic Cancer Center Translational Therapy Lab (TTL) along with 
serum (red top tubes) for measure of cytokines that can reflect immune activation.  
 
Flow cytometry analysis of a fraction of the PBMC will detect surface markers that 
define lymphocyte subsets (NK, NKT, B, and T cells, both CD4 and CD8), as well as 
intracellular markers that define regulatory T cells (Foxp3) and proliferating cells 
(Ki67). All remaining PBMC will be cryopreserved in 10% DMSO and stored in liquid 
nitrogen for future testing, if subject agreed to future storage at the time of initial 
consent. 
 
Samples may be sent to laboratories outside of the University of Minnesota in cases 
where testing is not available internally as embedded in the patient consent form. 
 


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9 
Study Agents 
9.1 FT596 
FT596 is an investigational product and can only be used and administered under 
an FDA-approved protocol. For the purposes of this study FT596 is provided by 
Fate Therapeutics.  
FT596 will be provided as a cryopreserved bag, thawed at the site of 
administration and administered as an IV infusion via gravity. FT596 must be 
administered using a Fate approved intravenous administration set with an in-
line filter (170-260 micron).  
Refer to the FT596 Storage, Handling, and Administration Guidance for 
additional details. 
 
Refer to Section 7 for potential toxicities. 
 
9.2 Rituximab (Rituxan or an FDA approved biosimilar, e.g. Truxima and 
Ruxience)  
Trade names:  Rituxan®, Truxima®, and Ruxience® 
Classification:  Monoclonal Antibody, Antineoplastic Agent 
Category:  Biological Response Modifier Agent 
Dosage and Administration Schedule:  For the purposes of the study, 
rituximab and rituximab biosimilars 375 mg/m2 IV is administered per institutional 
guidelines on 2-3 days prior to FT596.  
Dose Forms and Strengths:  refer to specific product prescribing information 
Availability:  Available by prescription 
Warnings and Precautions:  
 
Tumor lysis syndrome – administer prophylaxis and monitor renal function 
 
PML - monitor neurologic function. Discontinue rituximab 
 
Hepatitis B reactivation with fulminant hepatitis, sometimes fatal – screen 
high risk patients and monitor HBV carriers during and several months after 
therapy. Discontinue rituximab if reactivation occurs. 
 
Cardiac arrhythmias and angina can occur and can be life threatening. 
Monitor patients with these conditions closely. 
 
Bowel obstruction and perforation - evaluate complaints of abdominal pain. 
 
Do not administer live virus vaccines prior to or during rituximab. 
 
Monitor CBC at regular intervals for severe cytopenias 
 
Pregnancy Category C 
 
 


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Expected Toxicities: 
 
 
Refer to individual product prescribing information for additional information: 
 Rituxan® https://www.gene.com/download/pdf/rituxan_prescribing.pdf 
 Truxima® https://www.truxima.com/globalassets/truxima-dtc/pdfs/truxima-
prescribing-information.pdf 
 Ruxience™ http://labeling.pfizer.com/ShowLabeling.aspx?id=12090 
10 Adverse Event Monitoring, Documentation, and Reporting 
For the purposes of the study the FT596 in combination with rituximab (Rituxan and 
FDA approved biosimilars) is considered the investigational product.  
 
For the reminder of the section rituximab is a blanket term for Rituxan and any FDA 
approved biosimilars.  
 
Toxicity and adverse events will be classified and graded according to NCI's Common 
Terminology Criteria for Adverse Events V 5.0 (CTCAE) and reported on the schedule 
below. A copy of the CTCAE can be downloaded from the CTEP home page.   
(https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/CTCAE_v
5_Quick_Reference_5x7.pdf) 
 
Rituximab (Rituxan and FDA approved biosimilars) 
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) 
 allergic reaction with second 
and later infusions (same 
symptoms as under common) 
 low white blood cell 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 


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An exception to the use of CTCAE will be for the assessment of cytokine release 
syndrome (CRS). Individual adverse events which are associated with CRS will be 
graded per CTCAE; however the ultimate assessment will be made using a revised 
grading system for CRS as presented by Lee et al (Lee 2019).   
ASTCT Cytokine Release Syndrome Consensus Grading System a 
CRS Parameter 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Fever b 
Temperature ≥38˚C 
Temperature ≥38˚C 
Temperature ≥38˚C 
Temperature ≥38˚C 
With either: 
Hypotension 
None 
Not requiring 
vasopressors 
Requiring 
vasopressors 
with/with-out 
vasopressin 
Requiring multiple 
vasopressors 
(excluding 
vasopressin) 
And/or c 
Hypoxia 
None 
Requiring low-flow 
nasal cannula d or 
blow-by 
Requiring high-flow 
nasal cannula, 
facemask, 
non-rebreather mask, 
or venturi mask 
Requiring positive 
pressure 
(e.g., CPAP, 
BiPAP, intubation 
and mechanical 
ventilation) 
ASTCT, American Society for Transplantation and Cellular Therapy; BiPAP, bilevel positive airway pressure; 
CPAP, continuous positive airway pressure; CRS, cytokine release syndrome; NCI CTCAE, National Cancer 
Institute Common Terminology Criteria for Adverse Events. 
a Organ toxicities associated with CRS may be graded according to NCI CTCAE v5.0, but they do not influence 
CRS grading. 
b Fever is defined as temperature ≥38°C not attributable to any other cause. In subjects who have CRS then 
receive antipyretics or anti-cytokine therapy such as tocilizumab or steroids, fever is no longer required to grade 
subsequent CRS severity. In this case, CRS grading is driven by hypotension and/or hypoxia. 
c 
CRS grade is determined by the more severe event: hypotension or hypoxia not attributable to any other cause. 
For example, a subject with temperature of 39.5°C, hypotension requiring one vasopressor and hypoxia 
requiring low flow nasal cannula is classified as having Grade 3 CRS. 
d Low-flow nasal cannula is defined as oxygen delivered at >6 liters/minute. Low flow also includes blow-by 
oxygen delivery, sometimes used in pediatrics. High-flow nasal cannula is defined as oxygen delivered at 
>6 liters/minute. 
Source: Lee et al. 2019. 
 
The following definitions of adverse events (AEs) and serious adverse events (SAEs) 
will determine whether the event requires expedited reporting via the OnCore SAE 
Report Form in addition to routine documentation in the OnCore AE case report form 
(CRF).  
10.1 Adverse Event Terminology 
Adverse Event:  Any untoward medical occurrence associated with the use of a 
drug in humans, whether or not considered drug related. 
 
Serious Adverse Event:  An adverse event is considered “serious” if, in the view 
of either the investigator or sponsor, it results in any of the following outcomes:  
 Death 
 A life-threatening adverse event 
 Inpatient hospitalization or prolongation of existing hospitalization 


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 A persistent or significant incapacity or substantial disruption of the ability 
to conduct normal life functions 
 A congenital anomaly/birth defect 
Important medical events that may not result in death, be life-threatening, or 
require hospitalization may be considered serious when, based upon 
appropriate medical judgment, they may jeopardize the patient or subject and 
may require medical or surgical intervention to prevent one of the outcomes 
listed in this definition.  
 
Unexpected Event: An adverse event or suspected adverse reaction is 
considered “unexpected” if it is not listed in the investigator brochure or is not 
listed at the specificity or severity that has been observed; or, if an investigator 
brochure is not required or available, is not consistent with the risk information 
described in the general investigational plan or elsewhere in the current 
application, as amended.  
 
The categories for AE attribution to study treatment are as follows:  
 Definite – clearly related 
 Probable – likely related 
 Possible – may be related 
 Unlikely – doubtfully related 
 Unrelated – clearly not related 
 
The following definitions are from the Masonic Cancer Center’s Standard 
Operating Procedure (SOP) Deviation Reporting: 
 
Major Deviation: A deviation or violation that impacts the risks and benefits of the 
research; may impact subject safety, affect the integrity of research data and/or 
affect a subject’s willingness to participate in the research. Deviations that place a 
subject at risk, but do not result in harm are considered to be major deviations. 
 
Minor Deviation: A deviation or violation that does not impact subject safety, 
compromise the integrity of research data and/or affect a subject’s willingness to 
participate in the research. 
10.2 AE Documentation Requirements 
Adverse event collection for the purposes of this study will focus on events felt to 
be related to FT596 and rituximab or events that cannot be attributed to other 
causes (i.e. transplant-related, co-morbidities).  
 


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Monitoring for adverse events will begin with the first dose of rituximab through the 
End of Treatment visit after FT596. 
 
Adverse event documentation for the purposes of this study will focus on  
 expected toxicities felt to be related to rituximab 
 expected toxicities felt to be related to the FT596  
 unexpected adverse events that cannot be attributed to the transplant procedure 
or other causes (i.e. underlying disease, co-morbidities) 
 
For the purposes of this study, adverse event documentation requirements in 
OnCore will be based on grade, expectedness and relationship to the 
investigational product (FT596 and rituximab): 
 
After the End of Treatment visit, monitoring for adverse events will become less 
frequent based on the schedule in Section 8.1 and only events that are 
unexpected and at least possibly related to FT596 will be documented upon 
knowledge.  
10.3 SAE Documentation and Reporting 
Any event meeting the definition of an SAE must be documented using the 
paper MCC SAE Report Form. 
 
Any event meeting the definition of serious must be reported to Masonic Cancer 
Center Multisite Program Manager within 24 hours of knowledge. Refer to 
Section 10.6. 
10.4 Dose Limiting Toxicity and Excessive Toxicity (Stopping Rule Events) 
Documentation and Reporting Requirements 
All patients enrolled in Components 1 and 2 are monitored for dose limiting 
toxicity (DLT) and excessive toxicity (early stopping events) specific to the 
Component. Refer to Section 12 for definitions. (ONLY POST FT596 EVENTS 
COUNT) 
 
 
Grade 1 
Grade 2 
Grade 3 
Grade 4 and 5 
Expected or 
Unexpected 
Expected 
Unexpected 
Expected 
Unexpected 
Expected or 
Unexpected 
Unrelated 
Unlikely 
Not required 
Required 
Required 
Required 
Required 
Required 
Possible 
Probable 
Definite 
Not required 
Required 
Required 
Required 
Required 
Required 


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In addition to documenting the event in the study’s CRF’s, all DLT and SR events 
are to be documented on the Event Form found in OnCore per Masonic Cancer 
Center procedures. 
 
An event that counts as a DLT does not necessarily constitute a SAE and should 
be reported as such only if they meet the criteria for reporting as defined in 
Section 10.5. 
10.5 Documentation of Death and Reporting Requirements 
Deaths during the treatment and follow-up period, including due to disease, will be 
recorded as an SAE and reported per Section 10.6. Deaths due to disease should 
be recorded as a Grade 5 Neoplasm.  
 
In addition, the death date and cause must be documented in the patient follow-up 
tab in OnCore upon knowledge using the comment field in the survival status 
section to record the cause. 
10.6 Institutional Event Reporting Table 
 
Event Type 
Reporting Timeframe 
Form to Use 
Report to 
Any event meeting the 
definition of serious and all 
patient deaths 
Within 24 hours of 
knowledge 
Paper SAE 
Report Form 
 
For Participating Sites: 
Masonic Cancer Center (MCC) 
Multisite Program Manager  
affilates@umn.edu  
 
Local institutional IRB or other 
entities per institutional policies 
and guidelines 
 
 
Dose Limiting Toxicities  
Within 24 hours of 
knowledge 
DLT Event Form 
in OnCore 
Stopping Rule Events 
(Excessive Toxicity) 
Within 24 hours of 
knowledge 
Stopping Rule 
Event Form in 
OnCore 
Major Deviations, as 
defined in Section 10.1. 
Within 5 working days 
of knowledge 
Deviation Report 
Form in OnCore 
Minor Deviations, as 
defined in Section 10.1. 
Per Institutional Policy 
n/a (record in 
Deviations Tab) 
For UMN MCC: Report to the 
study’s regulatory specialist 
 
For Participating Sites: minor 
deviations are not reportable to 
the MCC Multisite Manager. 
Report to local institutional IRB or 
other entities per institutional 
policies and guidelines. 
*events occurring at the University of Minnesota are reported to the study’s Regulatory Specialist who will submit to 
other entities as usual 
Individual institutional sites are responsible for reporting any event meeting local 
reporting requirements to their institutional IRB and/or other research oversight 
committees. 
 
 


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10.7 Expedited MCC Reporting Requirements (MCC) 
As the study sponsor, the Masonic Cancer Center has the following expedited 
reporting responsibilities for select events reported in Section 10.6: 
 
 
11 Study Data Collection and Monitoring 
11.1 Data Management 
This study will collect regulatory and clinical data using University of Minnesota 
CTSI’s instance of OnCore® (Online Enterprise Research Management 
Environment).  
 
The OnCore database resides on dedicated secure and PHI compliant servers. All 
relevant AHC IS procedures related for PHI compliant servers (as required by the 
Center of Excellence for HIPAA Data) apply to OnCore databases. The informatics 
team grants the IRB approved study team members access to data. 
 
Agency 
reporting to 
Criteria for reporting 
Timeframe 
Form to Use 
Submission 
address/email 
address 
Advarra  (IRB of 
Record) 
unanticipated problems involving risks to subjects or 
others; unanticipated adverse device 
effects; protocol violations that may affect the subjects’ 
rights, safety, or well-being and/or the completeness, 
accuracy and reliability of the study data; subject death; 
suspension of enrollment; or termination of the study  
promptly and 
no later than 2 
weeks (10 
business days) 
from the time 
the investigator 
learns of the 
event 
Refer to the Advarra 
IRB Handbook 
Advarra via study 
specific CIRBI Link 
UMN IRB 
Refer to Submitting Updates in ETHOS – External IRB Study/Site 
FDA 
 
Unexpected and fatal or unexpected and life 
threatening suspected adverse reaction 
no later than 7 
Calendar Days 
MCC SAE Report 
Form 
Submit to FDA as an 
amendment to IND  
with a copy to each 
participating site 
and Fate Therapeutics 
 
1) Serious and unexpected suspected adverse reaction 
or 
2)  increased occurrence of serious suspected adverse 
reactions over that listed in the protocol or investigator 
brochure or 
3) findings from other sources (other studies, animal or 
in vitro testing) 
no later than 15 
Calendar-Days 
1) All other events per CFR 312.33 
2 )An annual manufacturing update, including for each 
new lot of the investigational biologic used in clinical 
trials, the lot number, the results of all tests performed 
on the lot, and the specifications when established (i.e., 
the range of acceptable results) (21 CFR 312.23(a)(7)) 
At time of IND 
annual report 
Summary format 
Submit as part of the 
IND annual report 
U of MN 
Institutional 
Biosafety 
Committee 
Any significant research-related accidents and 
illnesses involving potentially hazardous biological 
agents subject to IBC purview 
As soon as 
possible 
(within 24 
hours is ideal) 
IBC Incident 
Report 
Via eProtocol 


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Additional immune monitoring data about correlative laboratory samples 
generated by the Masonic Cancer Center Translational Therapy Laboratory (TTL) 
from the protocol-directed correlative research samples is stored in their 
Laboratory Information Management System (LIMS). The LIMS database 
application is also stored on a production server located in the UMN datacenter 
(WBOB) and is managed by the Academic Health Center 
 
Key study personnel are trained on the use of OnCore and will comply with protocol 
specific instructions embedded within the OnCore. 
11.2 Case Report Forms 
Participant data will be collected using protocol specific electronic case report 
forms (e-CRFs) developed within OnCore based on its library of standardized 
forms. The e-CRF will be approved by the study’s Principal Investigator and the 
Biostatistician prior to release for use. The Study Coordinator or designee will be 
responsible for registering the patient into OnCore at time of study entry, 
completing e-CRFs based on the patient specific calendar, and updating the 
patient record until patient death or end of required study participation.  
11.3 Data and Safety Monitoring Plan (DSMP) 
The study’s Data and Safety Monitoring Plan will be in compliance with the 
University of Minnesota Masonic Cancer Center's Data & Safety Monitoring Plan 
(DSMP), which may be accessed at http://z.umn.edu/dmsp.  
 
For the purposes of data and safety monitoring, this study is classified as high risk 
(under a locally held IND). Therefore, the following requirements will be fulfilled at 
the University of Minnesota and at participating sites: 
 At least quarterly review of the study’s progress by the Masonic Cancer Center 
Data and Safety Monitoring Council (DSMC). 
 The University of Minnesota (lead site) Principal Investigator will comply with 
at least twice yearly monitoring of the project by the Masonic Cancer Center 
monitoring services. 
 The local site PIs will comply with at least twice yearly monitoring of the project 
by each site’s internal monitoring staff. 
 The University of Minnesota (lead site) Principal Investigator will oversee the 
submission of all reportable adverse events per Section 10.7 to the Masonic 
Cancer Center’s SAE Coordinator, the University of Minnesota IRB; and 
oversee the submission of all reportable adverse events to the FDA  
 The University of Minnesota (Sponsor) and the MCC CTO have oversight 
responsibility for trial monitoring at affiliate sites. 
 


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IND Annual Reports 
In accordance with regulation 21 CFR § 312.33, the IND sponsor (Dr. Bachanova) 
will submit a progress report annually. The report is submitted within 60 days of 
the anniversary date that the IND went into effect. A copy of the report will be 
provided to Fate Therapeutics. Additional annual reporting requirements are found 
in the FDA Acknowledgment of Receipt of IND dated March 25, 2020.  
11.4 Participating Site Monitoring 
The PI (Dr. Bachanova) with the CTO has oversight responsibility for trial 
monitoring at participating sites.  
 
Participating sites must self-monitor using the Masonic Cancer Center Data and 
Safety Monitoring Plan (https://www.cancer.umn.edu/for-researchers/clinical-
investigator-resources/mcc-dsmp). Alternately, participating sites that are an NCI 
designated Cancer Center may self-monitoring using their NCI approved Data and 
Safety Monitoring Plan.  
 
The investigator will permit study-related monitoring, audits, and inspections by the 
study’s Principal Investigator/IND sponsor and/or any designees, the local IRB, 
government regulatory bodies, and University of Minnesota compliance groups. 
The investigator will make available all study related documents (e.g. source 
documents, regulatory documents, data collection instruments, study data, etc.). 
The investigator will ensure the capability for inspections of applicable study-
related facilities (e.g. pharmacy, diagnostic laboratory, etc.) will be available for 
trial related monitoring, audits, or regulatory inspections. 
11.5 Teleconferences – Lead Site and Participating Sites 
Regular teleconferences will be held to facilitate communication between 
participating sites regarding the study’s progress, patient updates, summary of 
safety reports, case report form completion, and other issues for discussion. The 
University of Minnesota Participating Sites Manager is responsible for arranging 
these teleconferences and preparing the agenda. Meetings will occur every 2 
weeks; however, these may be scheduled more or less frequently at the discretion 
of the lead institution. Participation of a minimum of one representative from each 
affiliate site is expected. These teleconferences are in addition to other previously 
described site interactions including centralized patient registration, institutional 
and MCC required reporting of safety related issues, case report form completion 
in the study’s central database (OnCore) and affiliate oversight through self-
monitoring in compliance with the Masonic Cancer Center’s Data and Safety 
Monitoring plan.  


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11.6 Record Retention 
The investigator will retain study records including source data, copies of case 
report forms, consent forms, HIPAA authorizations, and all study correspondence 
in a secured facility until permission is received that the documents are no longer 
needed.  
 
Please contact the CTO before destroying any study related records. 
 
 
12 Statistical Considerations  
12.1 Study Designs 
This study consists of two components. The 1st component is a Phase I clinical trial 
to identify the maximum tolerated dose (MTD) of FT596 at Day 30 post FT596 
infusion. The second component is a Phase I clinical trial to identify the MTD of 
FT596 at Day 7 post FT596 infusion. Rituximab is given 2-3 days before FT596. In 
addition to identifying the MTD and providing preliminary estimates of safety, 
secondary objectives include providing preliminary descriptive estimates of efficacy 
such as progression-free survival, relapse and non-relapse mortality along with 
their error measurements. Correlative objectives include measurement of the 
persistence of FT596 in blood after each FT596 infusion by immunophenotyping 
and PCR up to 1 year, the association of FT596 persistence with safety and anti-
tumor activity.  
 
Component 1 will identify the MTD of FT596 when given as a single dose at Day 
30. Up to three FT596 dose levels are planned (Dose Level 1: 9x107 cells/dose, 
Dose Level 2: 3x108 cells/dose, Dose Level 3: 9x108 cells/dose with a Dose 
Level - 1: 3x107 cells/dose tested only if DLT at DL1).  
 
Component 1 dose limiting toxicity is defined as any of the following events 
within 28 days after the FT596 dosing based on CTCAE v5: 
 
Grade 4 hematologic toxicity lasting > 7 days (not including lymphopenia)  
 
Grade 4 non-hematologic toxicity  
 
Grade ≥3 FT596 Infusion Related Reaction 
 
Grade 2 acute GVHD that requires steroid therapy >7 days or progression 
after 3 days of steroids or has partial response after 14 days of treatment 
 
Grade ≥3 acute GVHD 
 
Grade 4 cytokine release syndrome (CRS) 
 
Grade 3 CRS that does not resolve to < Grade 2 in 72 hours 
 
Grade 3 neurotoxicity 


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 
Grade 3 organ toxicity involving vital organs; cardiac, central nervous system 
and pulmonary that lasts for longer than 7 days including Grade 3 
Investigations (laboratory values) of any duration that indicate damage to 
vital organs.  
 
Any Grade 3 non-hematological toxicity that does not resolve to ≤Grade 2 
within 72 hours; excepting Grade 3 renal and hepatic toxicity which may take 
up to 7 days to resolve to ≤Grade 2 
 
The MTD will be determined by using a modified Continual Reassessment Method 
(CRM). (Goodman 1995) The CRM uses a power model for the probability of DLT 
at each dose, where the probability of toxicity at dose i is modeled as piexp(α)  
where pi is a constant and α is distributed a priori as a normal random variable with 
mean 0 and variance 2.  The goal of this CRM will be to identify one of the 3 dose 
levels corresponding to the desired maximum acceptable toxicity rate of ≤25%. 
 
Initial estimates of toxicity or the “skeleton” estimates are provided by the clinician.  
The initial estimates or prior probability of toxicity are listed as 1%, 3%, and 6% for 
doses 1, 2 and 3, respectively. As the study progresses, the CRM will continually 
update the estimates of the toxicity probabilities.   
 
Patients are enrolled in cohorts of 3 starting at Dose Level 1. A minimum of 28 days 
will separate each cohort. For Dose Level 1 a minimum of 28 days will separate 
each patient to assess for dose limiting toxicity (DLT). In subsequent cohorts, the 
1st and 2nd patient will be separated by at least 28 days and at least 14 days will 
separate the 2nd and 3rd patient. Enrollment will continue in cohorts of 3 and each 
new cohort of 3 will be sequentially assigned to the most appropriate dose based 
on the updated toxicity probabilities after the 3rd patient from the previous cohort 
has reached 28 days. The MTD will be identified when the total sample size of 18 
is exhausted or 6 patients are sequentially enrolled at the same dose. A maximum 
of 18 patients is used in part due to low expected toxicity. The function ‘crm’ from 
the R package ‘dfcrm’ will calculate posterior means of toxicity probabilities.  The 
CRM uses a Bayesian framework that combines experience from patients in the 
earlier part of the trial with the clinician’s initial best estimate of the toxicity rates at 
each dose level to estimate a dose level that best corresponds to the target toxicity 
of ≤25%. Dose escalation of more than one level is not permitted with this design.  
 
Component 2 will use a similar design but identify the MTD of FT596 when given 
as a single dose at Day 7. Up to two dose levels of FT596 are planned (1 Dose 
Level below the MTD from component 1 and the MTD from component 1) so any 
two sequential dose levels of the following may be included (Dose Level -1: 3x107 


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cells/dose, Dose Level 1: 9x107 cells/dose, Dose Level 2: 3x108 cells/dose, Dose 
Level 3: 9x108 cells/dose).  
 
The DLT events for Component 2 are the same as in Component 1 except for the 
addition of: 
 Non-engraftment by Day 28 post-transplant 
 
The MTD will be identified in the same fashion as Component 1 except that the 
initial estimates or prior probability of toxicity may be slightly higher due to the 
infusion of cells at Day 7 plus the additional possible DLT event. Assuming that we 
start at Dose Level 2, the skeleton probabilities might be listed as 5% and 10% for 
doses 2 and 3, respectively. The target toxicity level will still be ≤25%. As in 
Component 1, the CRM will continually update the estimates of the toxicity 
probabilities of both doses; first at the end of 28 days post infusion for each of the 
first three patients; and at the end of the of 28 day follow-up for the last patient in 
each of the 3 patient cohorts beyond the initial 3 patients. A minimum of 28 days 
will separate each patient in the 1st cohort to assess for dose limiting toxicity (DLT). 
In subsequent cohorts, the 1st and 2nd patient will be separated by at least 28 days 
and at least 14 days will separate the 2nd and 3rd patient. 
 
As in Component 1, each new cohort of three patients will be sequentially assigned 
to the most appropriate dose based on the updated toxicity probabilities, and the 
MTD will be identified when a total sample size of 18 is exhausted or 6 patients are 
sequentially enrolled at the same dose.  
12.2 Sample Size 
Due to the low expected toxicity, a maximum of 18 patients will be enrolled during 
component 1. Based on the simulations from table 1, this should be sufficient and 
safe to define the MTD for component 1. Based on the simulations from table 2, 
component 2 should also be sufficient and safe to define the MTD. Enrollment will 
most likely include 12 patients under each component but could range from 2 to 
18 patients. With expected enrollment of 12-18 patients/year, accrual for each 
component should be complete within 1.5 years. So after combining both trials, 
accrual should be complete in 2.5-3 years.  
 
 
 
 
 
 
 
Table 1. Operating characteristics for CRM (component 1) 
 
Cells/
dose 
Expected DLT 
Excessive DLT 
True 
Probability 
Probability of 
dose 
Patient 
Number 
True 
Probability 
Probability of 
selecting dose 
Patient 
Number 
9x107 
1% 
0% 
3 
10% 
15% 
6 
3x108 
3% 
0% 
3 
25% 
51% 
6 
9x108 
6% 
100% 
6 
40% 
34% 
6 


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12.3 Statistical Analysis  
The MTD will be determined in Component 1 and Component 2 per the design. All 
other endpoints including safety, progression-free survival, relapse, non-relapse 
mortality, toxicity rates and other clinical activity will be estimated descriptively. This 
will include simple frequencies, proportions, means, standard deviations/standard 
errors, medians and ranges.  
12.4 Monitoring Guidelines  
Monitoring guidelines will be in place to monitor events separately for each 
component separately. Stopping guidelines will be enacted using a continuous 
monitoring strategy based on an adaptation of Pocock stopping boundaries. 
(Ivanova 2005) In the event that the stopping rule is triggered, enrollment will be 
halted. The event will be reviewed by the study team with follow-up reporting of the 
findings to the FDA and IRB before enrollment is restarted. 
 
The rules are based on the time from transplant and occurring after the 
FT596 infusion. 
  
12.4.1 Mortality by Day 100  
Enrollment will be halted and reviewed by the study team with follow-up notification 
to the FDA and IRB of the findings before enrollment is restarted. 
 
12.4.2 Grade III-IV Acute GVHD by Day 100  
Enrollment will be halted and reviewed by the study team with follow-up notification 
to the FDA and IRB of the findings before enrollment is restarted. 
 
12.4.3 Any Grade 4 FT596 Infusion Related Reaction 
Enrollment will be halted and reviewed by the study team with follow-up notification 
to the FDA and IRB of the findings before enrollment is restarted. 
 
 
 
Table 2. Operating characteristics for CRM (likely scenario: component 2) 
 
Cells/
dose 
Expected DLT 
Excessive DLT 
True 
Probability 
Probability of 
dose 
Patient 
Number 
True 
Probability 
Probability of 
selecting dose 
Patient 
Number 
3x108 
5% 
0% 
6 
25% 
74% 
6 
9x108 
10% 
100% 
6 
40% 
26% 
6 


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12.4.4 Any Two Grade 4 Dose Limiting Toxicities (DLTs)  
If two Grade 4 DLTs occur, enrollment will be halted and reviewed by the study 
team with follow-up notification to the FDA and IRB of the findings before 
enrollment is restarted. 
 
12.4.5 Grade 4 Lymphopenia (<200 cells/uL) at Day 100  
The goal is to construct a boundary based on lymphopenia such that the probability 
of early stopping is at most 10% if the rate is equal to 20% and our sample size is 
at most 18. With these stipulations, the trial will be stopped and reviewed if 3/4, 
4/7, 5/10, 6/13 or 7/17 patients at any time have Grade 4 related lymphopenia at 
Day 100. 
 
12.4.6 Engraftment Failure by Day 28 (Component 2 only) 
Enrollment will be halted to Component 2 and reviewed by the study team with 
follow-up notification to the FDA and IRB of the findings before enrollment is 
restarted. 
 
 
13 Conduct of the Study 
13.1 Good Clinical Practice 
The study will be conducted in accordance the appropriate regulatory 
requirement(s). Essential clinical documents are maintained to demonstrate the 
validity of the study and the integrity of the data collected. Master files should be 
established at the beginning of the study, maintained for the duration of the study 
and retained according to the appropriate regulations.  
13.2 Ethical Considerations 
The study will be conducted in accordance with ethical principles founded in the 
Declaration of Helsinki. The IRB will review all appropriate study documentation in 
order to safeguard the rights, safety and well-being of the patients. The study will 
only be conducted at sites where IRB approval has been obtained. The protocol, 
consent, written information given to the patients, safety updates, progress reports, 
and any revisions to these documents will be provided to the IRB by the 
Investigator.  
 
 
 


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Musolino A, Naldi N, Bortesi B, et al. Immunoglobulin G fragment C receptor polymorphisms 
and clinical efficacy of trastuzumab-based therapy in patients with HER-2/neu–positive 
metastatic breast cancer. J Clin Oncol. 2008; 26:1789-1796. 
Neelapu SS, Tummala S, Kebriaei P, et al. Chimeric antigen receptor T-cell therapy - 
assessment and management of toxicities. Nat Rev Clin Oncol. 2018; 15(1):47-62. 
Porrata LF, Inwards DJ, Micallef IN et al  Interleukin-15 affects patient survival through natural 
killer cell recovery after autologous hematopoietic stem cell transplantation for non-Hodgkin 
lymphomas.Clin Dev Immunol. 2010;2010:914945. 
Rituxan® https://www.gene.com/download/pdf/rituxan_prescribing.pdf 
Romee R, Foley B, Lenvik T, et al. NK cell CD16 surface expression and function is regulated 
by a disintegrin and metalloprotease-17 (ADAM17). Blood. 2013; 121:3599-3608. 
Ruxience™ http://labeling.pfizer.com/ShowLabeling.aspx?id=12090 
Shi J, Tricot G, Szmania S Infusion of haplo-identical killer immunoglobulin-like receptor ligand 
mismatched NK cells for relapsed myeloma in the setting of autologous stem cell 
transplantation.Br J Haematol. 2008 Dec;143(5):641-53 
Truxima® https://www.truxima.com/globalassets/truxima-dtc/pdfs/truxima-prescribing-
information.pdf 
Vose, J. M. et al. Phase III randomized study of rituximab/carmustine, etoposide, cytarabine, and 
melphalan (BEAM) compared with iodine-131 tositumomab/BEAM with autologous hematopoietic 
cell transplantation for relapsed diffuse large B-cell lymphoma: results from the BMT CTN 0401 
trial. J. Clin. Oncol. 31, 1662-1668 (2013).  
Yescarta® (axicabtagene ciloleucel) suspension for intravenous infusion [Prescribing 
Information]. Santa Monica, CA. Kite Pharma, Inc; 2019. 
 


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Appendix I – LUGANO 2014 CLASSIFICATION: TUMOR RESPONSE 
ASSESSMENT IN LYMPHOMA  
Method of Assessment 
Assessments regarding sites of disease in subjects with lymphoma based on clinical, laboratory and 
radiographic evaluation are summarized in Table A. Positron emission tomography (PET)-computed 
tomography (CT) scan is the recommended radiographic modality for fluorodeoxyglucose (FDG)-avid, 
nodal lymphomas. For lymphomas that are not FDG-avid, anatomic CT scans should be used. 
Bone marrow assessments will be based on morphologic evaluation of bone marrow biopsies. 
Immunohistochemistry may be used to assess response if the sample is indeterminate by morphology.  
Bone marrow biopsies are not required if there is positive FDG-PET uptake in the bone marrow.  
Otherwise, in this study of subjects with relapsed/refractory lymphoma a bone marrow biopsy should be 
performed only under the following circumstances: 
 
A bone marrow biopsy is required at baseline if the subject had a history of bone marrow involvement 
with lymphoma prior to the start of study treatment; 
 
During the course of the study, if new abnormalities in the peripheral blood counts or blood smear 
cause clinical suspicion of bone marrow involvement with lymphoma; 
 
During the course of the study, a bone marrow biopsy must be performed to confirm a radiographic 
CR and show no morphologic evidence of disease, or be negative by immunohistochemistry if 
indeterminate morphology, to assign an overall response of CR. 
Table A - Lugano 2014 Classification: Criteria for Site Involvement  
Tissue Site  
Clinical  
FDG Avidity  
Test  
Positive Finding 
Lymph nodes 
Palpable 
FDG-avid histologies 
PET-CT 
Increased FDG uptake 
 
Non-avid disease 
CT 
Unexplained node 
enlargement 
Spleen 
Palpable 
FDG-avid histologies 
PET-CT 
Diffuse uptake, solitary mass, 
miliary lesions, nodules 
 
Non-avid disease 
CT 
>13 cm in vertical length, 
mass, nodules 
Liver 
Palpable 
FDG-avid histologies 
PET-CT 
Diffuse uptake, mass 
 
Non-avid disease 
CT 
Nodules 
CNS 
Signs, 
symptoms 
 
CT 
Mass lesion(s) 
 
 
MRI 
Leptomeningeal infiltration, 
mass lesions 
 
 
CSF 
assessment 
Cytology, flow cytometry 
Other (e.g., skin, 
lung, GI tract, bone, 
bone marrow) 
Site 
dependent 
 
PET-CT, a 
biopsy 
Lymphoma involvement 
CSF, cerebrospinal fluid; CT, computed tomography; FDG, fluorodeoxyglucose; MRI, magnetic resonance 
imaging; PET, positron emission tomography. 
a 
PET-CT is adequate for determination of bone marrow involvement and can be considered highly 
suggestive for involvement of other extralymphatic sites. Biopsy confirmation of those sites can be considered if 
necessary. 
Reference: Cheson 2014. 
 
 


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1 
TIMING OF ASSESSMENTS 
This is a post-transplant protocol. Assessments will be per institutional standard of care. 
2 
IDENTIFICATION AND FOLLOW-UP OF TUMOR LESIONS BY PET-CT SCAN 
Identification and follow-up of tumor lesions by PET-CT scans are based on focal uptake in nodal and 
extranodal sites that are consistent with lymphoma based on distribution and/or characteristics as visualized 
by anatomic CT scan. Unlike tumor assessments based exclusively on anatomic CT scan, no distinction 
between target and non-target lesions based on PET scans is required.   
3 
IDENTIFICATION AND FOLLOW-UP OF TUMOR LESIONS BY ANATOMIC CT SCAN 
3.1 
Target and Non-target Lesions 
Identification and follow-up of target lesions using anatomic CT scans should include up to six of the largest 
target nodes, nodal masses, or other lymphomatous lesions that are measurable in two diameters should 
be identified from different body regions representative of the subject’s overall disease burden. Where 
applicable, these should include mediastinal and retroperitoneal disease. Definitions of baseline 
measurable disease are as follows, lesions not fulfilling these definitions are designated non-measurable: 
 
Nodal lesion: must be greater than 15 mm in the longest diameter (LDi)   
 
Extranodal lesion: should be greater than 10 mm in the LDi   
Measurable extranodal disease may be included among the six representative measured lesions. Overall 
target lesion burden is expressed as the sum of the product of the perpendicular diameters (SPD). 
All other lesions including non-measurable disease and measurable disease beyond the six designated 
target lesions should be followed as non-measured disease as non-target lesions, e.g., cutaneous, GI, 
spleen, liver, kidneys, pleural or pericardial effusions, ascites, bone, and bone marrow. 
3.2 
Split Lesions and Confluent Lesions 
Lesions may split or may become confluent over time. In the case of split lesions from a designated target 
lesion, the individual products of the perpendicular diameters (PPD) for each split lesion should be summed 
together to represent the PPD derived from the initial target lesion; this PPD is added to the sum of the 
PPDs of the remaining lesions to determine target lesion SPD. If subsequent growth of any or all of these 
discrete nodes occurs, the nadir of each individual node is used to determine progression. 
In the case of confluent lesions from designated target lesions, the PPD of the confluent mass should be 
compared with the SPDs of the individual lesions. A >50% increase in PPD of the confluent lesion compared 
with the SPD of individual lesions would therefore constitute progressive disease. 
3.3 
Definitions of Tumor Response and Progression 
Target lesion responses will be categorized as complete response (CR), partial response (PR), stable 
disease (SD), or progressive disease (PD). 
For non-target lesions in the absence of quantitative measurement, responses will be characterized as 
follows: CR, Non-CR/Non-PD (corresponding to PR/MR/SD), or PD. 


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For both target and non-target lesions, a response category of not evaluable (NE) is provided for situations 
in which there is inadequate information to otherwise categorize response status. 
The best overall response (BOR) will be determined based on an overall evaluation of target lesions, non-
target lesions and new lesions as summarized in Table B. The BOR is defined as the best overall response 
recorded from the start of study treatment until disease progression or relapse. The baseline measurement 
will be taken as a reference for determinations of response. The nadir measurement will be taken as a 
reference for PD; this measurement constitutes the smallest measurement recorded, including the baseline 
measurement if this is the smallest measurement. 
Confirmation of overall response is not required. Confirmation of PD may be warranted, e.g., small FDG-
PET avid lesions that do not fulfill the dimensional criteria for PD but are confirmed to be progressive 
disease based on histologic examination or continued growth of the lesion. 
 
 


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Table B Lugano 2014 Classification: Response Categories 
Response 
Site 
PET-CT–Based Response 
CT-Based Response 
Complete 
Response 
 
Complete metabolic response 
Complete radiologic response (all of 
the following) 
Lymph nodes and 
extralymphatic sites 
Score 1, 2, or 3 a with or without 
a residual mass on 5PS b 
 
Target nodes/nodal masses must 
regress to ≤1.5 cm in 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 marrow 
Normal by morphology; if 
indeterminate, IHC negative 
Partial 
Response 
 
Partial metabolic response 
Partial remission (all of the following) 
Lymph nodes and 
extralymphatic sites 
Score 4 or 5 b with reduced 
uptake compared with baseline 
and residual mass(es) of any 
size 
≥50% decrease in SPD of up to 6 
target measurable nodes and 
extranodal sites 
At interim, these findings suggest 
responding disease 
When a lesion is too small to 
measure on CT, assign 5 mm × 5 
mm as the default value 
At end of treatment, these 
findings indicate residual disease 
When no longer visible, 0 × 0 mm 
For a node >5 mm × 5 mm, but 
smaller than normal, use actual 
measurement for calculation 
Non-measured lesions 
Not applicable 
Absent/normal, regressed, but 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 
uptake in normal marrow but 
reduced compared with baseline 
(diffuse uptake compatible with 
reactive changes from 
chemotherapy allowed). If there 
are persistent focal changes in 
the marrow in the context of a 
nodal response, consideration 
should be given to further 
evaluation with MRI or biopsy or 
an interval scan. 
Not applicable 
Stable 
Disease 
 
No metabolic response 
Stable disease 
Target nodes/nodal 
masses, extranodal 
lesions 
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 up to 6 dominant, 
measurable nodes and 
extranodal sites; no criteria for 
progressive disease are met 
Non-measured lesions 
Not applicable 
No increase consistent with 
progression 
Organ enlargement 
Not applicable 
No increase consistent with 
progression 
New lesions 
None 
None 
Bone marrow 
No change from baseline 
Not applicable 
 
 
 
 


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Table B Lugano 2014 Classification: Response Categories 
Response 
Site 
PET-CT–Based Response 
CT-Based Response 
Progressive 
Disease 
 
Progressive metabolic 
disease 
Progressive disease (requires at 
least 1 of the following) 
Individual target 
nodes/nodal masses 
Score 4 or 5 with an 
increase in intensity of 
uptake from baseline and/or 
PPD progression: 
Extranodal lesions 
New FDG-avid foci 
consistent with lymphoma at 
interim or end-of-treatment 
assessment 
An individual node/lesion must 
be abnormal with: 
LDi >1.5 cm and 
Increase by ≤50% from PPD 
nadir and 
An increase in LDi or SDi from 
nadir 
0.5 cm for lesions ≤2 cm 
1.0 cm for lesions ≤2 cm 
In the setting of splenomegaly, 
the splenic length must increase 
by >50% of the extent of its prior 
increase beyond baseline (e.g., 
a 15-cm spleen must increase to 
>16 cm). If no prior 
splenomegaly, must increase by 
at least 2 cm from baseline 
New or recurrent splenomegaly 
Non-measured lesions 
None 
New or clear progression of 
preexisting non-measured 
lesions 
New lesions 
New FDG-avid foci 
consistent with lymphoma 
rather than another etiology 
(e.g., infection, 
inflammation). If uncertain 
regarding etiology of new 
lesions, biopsy or interval 
scan may be considered 
Regrowth of previously resolved 
lesions 
A new node >1.5 cm in any axis 
A new extranodal site >1.0 cm in 
any axis; if <1.0 cm in any axis, 
its presence must be 
unequivocal and must be 
attributable to lymphoma 
Assessable disease of any size 
unequivocally attributable to 
lymphoma 
Bone marrow 
New or recurrent FDG-avid 
foci 
New or recurrent involvement 
5PS, 5-point scale; CT, computed tomography; FDG, fluorodeoxyglucose; IHC, immunohistochemistry; LDi, longest transverse 
diameter of a lesion; MRI, magnetic resonance imaging; PET, positron emission tomography; PPD, cross product of the LDi and 
perpendicular diameter; SDi, shortest axis perpendicular to the LDi; SPD, sum of the product of the perpendicular diameters for multiple 
lesions. 
a A score of 3 in many subjects indicates a good prognosis with standard treatment, especially if at the time of an interim scan. 
However, in trials involving PET where de-escalation is investigated, it may be preferable to consider a score of 3 as inadequate 
response (to avoid undertreatment). Measured dominant lesions: Up to six of the largest dominant nodes, nodal masses, and 
extranodal lesions selected to be clearly measurable in two diameters. Nodes should preferably be from disparate regions of the 
body and should include, where applicable, mediastinal and retroperitoneal areas. Non-nodal lesions include those in solid organs 
(e.g., liver, spleen, kidneys, lungs), GI involvement, cutaneous lesions, or those noted on palpation. Nonmeasured lesions: Any 
disease not selected as measured, dominant disease and truly assessable disease should be considered not measured. These sites 
include any nodes, nodal masses, and extranodal sites not selected as dominant or measurable or that do not meet the requirements 
for measurability but are still considered abnormal, as well as truly assessable disease, which is any site of suspected disease that 
would be difficult to follow quantitatively with measurement, including pleural effusions, ascites, bone lesions, leptomeningeal 
disease, abdominal masses, and other lesions that cannot be confirmed and followed by imaging. In Waldeyer’s ring or in extranodal 
sites (eg, GI tract, liver, bone marrow), FDG uptake may be greater than in the mediastinum with complete metabolic response, but 


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Table B Lugano 2014 Classification: Response Categories 
Response 
Site 
PET-CT–Based Response 
CT-Based Response 
should be no higher than surrounding normal physiologic uptake (e.g., with marrow activation as a result of chemotherapy or myeloid 
growth factors). 
b 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. 
Reference: Cheson 2014. 
 

ICF_001.pdf: 
 
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Veronika Bachanova , MD, PhD 
Advarra IRB Approved Version 14 Dec 2020 
Revised 14 Dec 2020 
 
INFORMED CONSENT FORM 
AND AUTHORIZATION TO USE AND DISCLOSE PROTECTED HEALTH 
INFORMATION 
 
Sponsor / Study Title: 
  
Veronika Bachanova, MD – University of Minnesota / 
MT2019-46: FATE FT596 with Rituximab as Relapse 
Prevention in High Risk Patients after Autologous 
Hematopoietic Stem Cell Transplantation for Non-
Hodgkin Lymphoma  
 
Protocol Number: 
 
2019LS230 (MT2019-46) 
 
Principal Investigator: 
(Study Doctor) 
 
Veronika Bachanova , MD, PhD 
  
Telephone: 
 
(612) 625-5469 
(612) 273-3000 (24 Hours) 
  
Address: 
University of Minnesota Medical Center, Fairview 
500 Harvard Street SE 
Minneapolis, MN    55455 
 
University of Minnesota Health Clinics and Surgery 
Center 
909 Fulton St SE 
Minneapolis, MN    55455 
 
 
Supported By: The research related expenses for this study are covered by National 
Institutes of Health (NIH) grants. Fate Therapeutics, is supplying the FT596 cell product 
without cost for the purposes of this study. 
 
Financial Interest Disclosure: This research is supported in part by Fate 
Therapeutics. The University of Minnesota has licensed certain aspects of FT596, the 
cell product being tested in this study to Fate Therapeutics. The University of Minnesota 
may benefit financially if the product is marketed in the future. This interest has been 
reviewed and managed by the University of Minnesota in accordance with its conflict of 
interest policies.  If you would like further information about this interest, please contact 
Jon Guden, Associate Director, Conflict of Interest Program, at jguden@umn.edu. 
 
If you are an employee or relative of an employee of this research center, you are under 
no obligation to participate in this study.  You/your family member may withdraw from 
the study at any time and for any reason, and neither you/your family member’s 
decision to participate in the study, nor any decision on your/their part to withdraw, will 
have any effect on your/your family member’s performance appraisal or employment at 
this clinical research center.  You/your family member may refuse to participate, or 


 
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Veronika Bachanova , MD, PhD 
Advarra IRB Approved Version 14 Dec 2020 
Revised 14 Dec 2020 
 
you/your family member may withdraw from the study at any time without penalty or 
anyone blaming you.  
 
If you are a student of the researcher, you are under no obligation to participate in this 
study.  You may withdraw from the study at any time and for any reason, and your 
decision to participate in the study, nor any decision on your part to withdraw, will have 
any effect on your performance or standing as a student.  You may refuse to participate, 
or you may withdraw from the study at any time without any penalty. 
 
Key Information About This Research Study 
The following is a short summary to help you decide whether or not to be a part of this 
research study. More detailed information is listed later on in this form. 
 
What is research? 
Study doctors and investigators are committed to your care and safety. There are 
important differences between research and treatment plans: 
• The goal of research is to learn new things in order to help groups of people in 
the future. Study doctors learn things by following the same plan with a number 
of subjects. You, as an individual, may or may not be helped by participating in a 
research study; however, your participation helps answer the research questions. 
• The goal of routine (standard) treatment is to treat your medical condition. 
Standard treatments are available from any doctor. 
 
Research and clinical care are often combined. One purpose of this consent document 
is to provide you clear information about the specific research activities of this study.  
 
Why am I being asked to take part in this research study? 
You are invited to take part in a research study because you have non-Hodgkin 
lymphoma and a transplant using your own blood cells is planned. Currently there is no 
standard of care treatment after transplant other than regular follow-ups and the use of 
the drug rituximab to prevent or reduce the chance of your cancer coming back after the 
transplant.  
 
The purpose of this consent form is to help you decide if you want to participate in the 
research study. 
 
You should not join this research study until all your questions are answered. 
 
Things to know before deciding to take part in a research study:   
• The decision to join or not join the research study will not cause you to lose any 
medical benefits. If you decide not to take part in this research study, your doctor 
will continue to treat you. 
• You may change your mind and take back (withdraw) your consent at any time 
during your participation in the study without penalty or loss of any benefits to 
which you are otherwise entitled. 
• Parts of this study involve standard medical care.   


 
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Veronika Bachanova , MD, PhD 
Advarra IRB Approved Version 14 Dec 2020 
Revised 14 Dec 2020 
 
• Other parts of this study may involve experimental (investigational) therapy or 
procedures that are being tested for a certain condition or illness. An 
investigational therapy is one that has not been approved by the U.S. Food and 
Drug Administration (FDA) to treat the condition or illness for which it is being 
studied. 
• After reading this consent form and speaking with the research staff, you should 
understand which parts of the study are investigational and which are standard 
medical care. 
• Your medical records may become part of the research record. If that happens, 
your medical records may be looked at and/or copied by Fate Therapeutics, Inc., 
which is the supplying the investigational cell therapy product FT596, the 
Institutional Review Board (IRB) reviewing this research study, as well as 
government agencies responsible for overseeing the conduct of the study, such 
as the FDA and health authorities from other countries. 
• Your medical insurance may be billed for any standard medical care you receive 
during the research study. If your insurance company is billed, then it may have 
access to the research records. Insurance companies may not pay for treatment 
that is part of a research study.   
 
If you take part in this research study, you will be asked to sign and date this consent 
form confirming that all of your questions about what the study is and what you will have 
to do during the study have been answered. By signing and dating, you are freely 
consenting to join this research study. You will be given a copy of your signed and 
dated consent form. If you decide not to take part in this research study, there may be 
other choices available to help treat your cancer. Ask the study doctor to discuss these 
choices with you. 
 
Study Treatment Overview 
Rituximab is a commonly used drug and can be given without being in a study (you may 
have received it in the past). It will be given at the usual dose as an intravenous 
infusion. It is given 2-3 days day before FT596 infusion to “prime” your immune system 
for the FT596 cells. It is given as an outpatient treatment, but if you are in the hospital, 
you will receive it as an inpatient treatment. 
 
FT596 is given as an infusion in your vein (intravenous). Depending on the dose level to 
which you are assigned, you may receive 1 or more bags per dose. Each bag should 
take approximately 15 minutes to infuse. The process is similar to a blood transfusion. 
You will be given acetaminophen (Tylenol®) and diphenhydramine (Benadryl®) before 
and a few hours after the FT596 to help prevent any unwanted reactions to the infusion. 
 
Why is this research being done? 
FT596 is produced by growing cells that come from a live, healthy human donor. The 
donor cells are treated in a laboratory with a process that turns them into a type of cell 
called an induced pluripotent stem cell, which means that these cells can be turned into 
any type of human cell. In this case, the cells are turned into Natural killer (NK) cells 


 
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Veronika Bachanova , MD, PhD 
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Revised 14 Dec 2020 
 
which are a specific type of lymphocyte.  Once prepared, they are then frozen and 
shipped to your study doctor’s office.  
 
FT596 is different from the NK cells that are already in your body because FT596 has 
been changed through a process known as cell engineering. This type of cell 
engineering uses viruses to change the coded building blocks of cells, known as DNA, 
so the changed cells will work differently than they otherwise would. The viruses used 
for this engineering are unlikely to cause any infections in humans. To engineer FT596, 
three proteins (described below) were added to the cells.  
• Chimeric antigen receptor (also called a CAR): this protein recognizes another 
protein called CD19, which is found on lymphoma cells, leukemia cells, and 
normal B-cells. FT596 has been engineered to bind to the cancer cells containing 
CD19; when the NK cells activate after being bound to a cancer cell, the NK cells 
will then kill the cancer cell. 
• hnCD16: this protein will bind to monoclonal antibodies, which are a type of 
medication commonly given to people with your kind of cancer.  
• IL-15/IL-15 receptor complex: this protein is intended to help the NK cells stay 
alive. 
 
As this is one of the first in humans study of FT596 in this population, this study is being 
done in 2 parts (components), each with its own purpose, although the tests evaluations 
and follow-up schedule are the same for both.  
 
Component 1 – FT596 given 30 days after transplant: In this part all subjects receive 
a single dose of rituximab followed 2-3 days later by a single infusion of FT596. Study 
treatment is given as an outpatient. Up to 3 dose levels of FT596 will be tested. The 
purpose of Component 1 is to determine which dose level of FT596 is safe.  
 
Component 2 – FT596 given 7 days after transplant: In this part all subjects receive 
a single dose of rituximab followed 2-3 days later by a single infusion of FT596. Two 
dose levels will be tested in this component (one dose level below the dose level 
identified in Component 1 and the dose level identified in Component 1. Study treatment 
may be given as an outpatient, but will be given in the hospital for subjects still in the 
hospital after their transplant. The purpose of Component 2 is to determine if giving 
FT596 shortly after a transplant is safe. 
 
You will be told which component of the study is enrolling and dose level of FT596 you 
will receive. 
 
How long will I be in this study? 
A single course of study treatment is given, either around 30 days after your transplant 
or around 7 days after your transplant. After the FT596 infusion you will have at least 
weekly clinic visits for 4 weeks to assess for side effects and check your blood counts.  
 
After the 4 weeks of frequent visits, follow-up for this study will match your standard of 
care 3 month, 6 month, and 12 month (1 year) follow-up visits after the transplant. 


 
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Veronika Bachanova , MD, PhD 
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Revised 14 Dec 2020 
 
Routine information obtained from these visits (physical exam results, lab work, disease 
response) will be recorded in the study record.  
 
Your direct participation in this research study is about 1 year from the transplant; 
however, as part of this study you must agree to take part in a long-term follow-up 
(LTFU) study. After your participation ends in this treatment study, follow-up will 
continue at least once a year either in person, or by mail or telephone for an update on 
your overall health and if you have any new diagnoses of immune related conditions (for 
example, rheumatoid arthritis), neurological changes or new cancers. You will receive a 
separate consent form for the LTFU study.  
 
What will I need to do to participate? 
After you hear about the study, read through the consent and have your questions 
answered, you will be asked to sign and date this consent form if you are interested in 
the study. By signing and dating this consent, you are giving permission for the study 
staff to review your medical record to determine if you qualify for the study. 
 
More detailed information about the study procedures can be found under “What 
happens if I say yes, I want to be in this research?” 
 
Is there any way that being in this study could be bad for me? 
Risks associated with FT-596 are based on experience with other NK cell products and 
may include: 
 
Infusion Related Reaction is a potential risk of both rituximab and FT596 during the 
infusion or shortly after. This reaction could be mild (skin irritation/rash) to life-
threatening (difficulty breathing/swelling of the face and throat). Medications are given 
before and after each infusion to lessen the risk of an allergic reaction. If a reaction 
occurs, the symptoms are treated with the appropriate medications. 
 
Cytokine release syndrome (CRS) is a serious systemic (whole body) inflammation 
response. CRS is seen with other types of cell therapies, but is not typically seen with 
NK cell therapies. Signs of CRS include fever, nausea, headache, rash, rapid heartbeat, 
low blood pressure, and trouble breathing. Most subjects who develop CRS have a mild 
reaction, but sometimes, the reaction may be severe or life threatening. CRS is treated 
with supportive care and steroids. 
 
More detailed information about the risks of this study can be found under “What are 
the risks of this study?  Is there any way being in this study could be bad for me? 
(Detailed Risks)” and in the “What happens to the information collected for the 
research?” section. 
 
Will being in this study help me in any way? 
If you agree to take part in this study, there may or may not be direct medical benefit to 
you. The information learned from this study may benefit other patients who are at an 
increased risk of relapse after a transplant.   


 
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Revised 14 Dec 2020 
 
 
What happens if I do not want to be in this research? 
You do not have to participate in this research. Giving FT596 is an extra investigational 
option after transplant. Regardless of whether or not you take part in this study, you will 
receive the usual care after an autologous transplant of regular follow-up visits with or 
without rituximab given every few months. It is your decision.  
 
Detailed Information About This Research Study 
The following is more detailed information about this study in addition to the information 
listed above. 
 
How many people will be enrolled in this study? 
This is study will enroll subjects through the University of Minnesota and one other 
Midwestern Cancer Center with about half of the enrollment occurring at each site. 
 
Component 1: It is expected 12 subjects are needed to determine a safe dose of 
FT596 at 30 days after transplant.  
 
Component 2: It is expected 12 subjects are needed to determine a safe dose of 
FT596 at 7 days after transplant. 
 
What happens if I say “Yes, I want to be in this research”? 
Participation in the study will include: 
• Screening Period: A screening period before you begin the transplant 
procedures. This study has very few requirements for taking part in it and will use 
the results of tests and evaluations done before the transplant. The main 
requirement for this study is that you are undergoing an autologous transplant 
and your disease has some features that may put you at a higher risk of relapse 
(your disease returning after the transplant). At this time, if you are interested in 
taking part in the study, you will be asked to sign and date this treatment consent 
(and the long-term follow-up consent form). 
The screening period will include tests to check for previous exposure to 
immunodeficiency virus (HIV), hepatitis B, and hepatitis C. If required by state 
law, the study doctor or study staff may report a positive test result to the local 
health department. 
• Confirmation of Study Participation: After the transplant, it will be confirmed 
that taking part in the study is still felt to be safe and that you are still interested in 
taking part. 
• Study Treatment Period: The study treatment period for this study depends are 
which part of the study you are enrolled in. This is explained in more detail below. 
Everyone receives a dose of rituximab followed 2 to 3 days later by an infusion of 
FT596 cells. A final study treatment visit occurs approximately 4 weeks (28 days) 
after receiving FT596.  
• Follow-up Period: Follow-up visits with your study doctor on a regularly 
scheduled basis will be done as part of your post-transplant care. This study has 
a follow-up period 1 year after the transplant and whenever possible, follow-up 


 
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visits for this study will be at the same time as routine post-transplant follow-up 
visits. 
• Long-Term Follow-Up: Because FT596 is a genetically modified cell product, 
follow-up for up to 15 years is required by the Food and Drug Administration. 
When you complete the follow-up directly related to this treatment study at 1 
year, you will be “transferred” to a separate long-term follow-up study. You are 
receiving a separate consent explaining the once yearly follow-up, either in 
person or by mail, telephone call or other means. 
 
Study Treatment Overview: 
Rituximab is a commonly used drug and can be given without being in a study (you 
have probably received it in the past). It will be given at the usual dose as an 
intravenous infusion. It is given 2-3 days day before the FT596 infusion to “prime” your 
immune system for the FT596 cells. It is given as an outpatient treatment, but if you are 
in the hospital, you will receive it as an inpatient treatment. 
 
FT596 is given as an infusion in your vein (intravenous). Depending on the dose level to 
which you are assigned, you may receive 1 or 3 bags. Each bag should take 
approximately 15 minutes to infuse. The process is similar to a blood transfusion. At 
certain points before and after you receive FT596, you will be given acetaminophen 
(Tylenol®) and diphenhydramine (Benadryl®) to help prevent any unwanted reactions to 
the infusion. 
 
Study Treatment Plan Assignment:  
After the transplant, it will be confirmed that taking part in the study is felt to be safe and 
that you are still interested in taking part. 
 
Everyone in this study receives 1 dose rituximab followed 2-3 days later by 1 dose of 
FT596 as described above. The timing in relation to the transplant and the dose of 
FT596 is what varies. 
 
The dose levels of FT596 are based on other ongoing research studies. Enrollment will 
be staggered such that one subject will be treated with FT596 and then a period of time 
must pass before the next subject is treated. This is to make sure there are no late side 
effects from the FT596 
 
In Component 1, FT596 is given 30 days after the transplant.  
 
Up to 3 dose levels of FT596 will be tested using a standard statistical design called 
3+3. Each dose level will enroll 3 subjects until either Dose Level 3 is reached or there 
is unacceptable toxicity. At the top dose level, 3 more subjects are treated to gain 
additional safety information. If all 3 dose levels are tested without any unacceptable 
side effect a total of 12 subjects would be treated (3+3+6).  
 
If at any time an unacceptable side effect occurs, additional subjects (up to 6) would be 
enrolled at the same dose plan to further evaluate the side effects to determine if it is 


 
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specific to one subject or if unacceptable side effects occur or other subjects. If no other 
side effects are seen and there are dose levels that have not been tested, enrollment 
may continue; however, in a future, 6 subjects would be treated at each dose level. As 
many as 18 subjects could be treated if 6 subjects need to be treated at each of the 3 
dose levels (6+6+6). 
 
The goal of Component 1 is to identify a safe dose level of FT596 for further testing.  
 
In Component 2, FT596 is given 7 days after the transplant. 
 
Component 2 tests two dose levels of FT596 based on what is learned in Component 1. 
It uses a different statistical plan call CRM. The first 3 subjects are treated at one dose 
level below the dose level identified in Component 1. For example, if Dose Level 3 is 
identified as the safe dose for Component 1, the 1st 3 subjects will receive FT596 at 
Dose Level 2. If no unacceptable side effects occur, the next 3 subjects are treated at 
the Component 1 dose (Dose Level 3 in the example). Subjects continue to be enrolled 
in groups of 3 at the most appropriate of the two dose levels until 6 subjects in a row are 
treated at Dose Level 3 or 18 subjects total are treated.   
 
The goal of Component 2 is to determine if giving FT596 shortly after a transplant is 
safe.  
 
Study Related Sample Collection (Research Related): 
Because this is a research study, you will have research blood samples taken at the time 
you sign and date this consent (before you receive the transplant chemotherapy, before 
rituximab, before and after FT596 and up to 6 times over the next 4 weeks. In addition, 
blood for research will be collected at the standard of care follow-up visits after transplant 
at 3, 6 and 12 months. Approximately 5 tablespoons of blood will be collected at each 
time point. The blood samples will be collected at the time you are having blood work for 
your medical care except for a small sample (about 2 teaspoons) collected about 30 
minutes after the FT596 infusion.  
 
Blood from the research samples will be tested and analyzed to look at your immune 
system and the effects of FT596. The testing may include testing using genetic markers 
to see how much and how long FT596 is present in your blood. This research will a 
better understanding of how FT596 works. If there are tests that cannot be done at the 
study site, blood may be sent to outside labs, including Fate Therapeutic labs. Any 
samples leaving the study site will not contain information that could directly identify you. 
 
If any blood left over from the collections described above, the extra blood may be 
stored for additional future research testing. This may include further tests about how 
FT596 works against cancer, or it may include tests about other cancer treatment or 
prevention methods. This testing may include future genetic testing.  
 
Information obtained from testing the samples will be used only for purposes of 
research and development. None of the research-related testing results will affect your 


 
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care or your participation in this study. The results will not be placed in your medical 
record and will not be given to your insurance company or employer unless required by 
law. Neither you nor your health insurance provider will be charged for the cost of 
research sample processing, storage or testing.  If the results from this study are 
published in a medical journal or presented at a scientific meeting, you will not be 
identified. 
 
Genome Testing and Handling of Genetic Information 
Biomarkers are substances in your body that may indicate something abnormal is 
happening in your body. Biomarkers may be tested as part of this study, including 
possible analysis of your genome (DNA).  
 
Your blood and/or your tumor tissue samples may be tested to find about possible 
mutations (permanent alterations) and other possible changes to your genome. Testing 
will not be done to determine whether any mutations are inherited.   
 
Studying the blood and tumor tissue samples from a large number of people may help 
researchers learn more about new treatments, cancer biology, and how mutations affect 
a person’s response to treatment. The genetic test results are not intended to be used 
to guide you or your doctors in making any health care decisions. Research performed 
on these samples may benefit other patients with cancer similar to yours. There are no 
plans to return the results of this research to you. 
 
The Genetic Information Nondiscrimination Act of 2008 generally makes it illegal in the 
United States for health insurance companies, group health plans, and most employers 
to discriminate against you on the basis of your genetic information. The law generally 
will protect you in the following ways:  
• Health insurance companies and group health plans cannot request your genetic 
information from this research; 
• Health insurance companies and group health plans cannot use your genetic 
information when making decisions regarding your eligibility or premiums; and 
• Employers with 15 or more employees cannot use your genetic information from 
this research when setting the terms of your employment. 
 
This United States federal law does not protect you against genetic discrimination by 
companies that sell life insurance, disability insurance, or long-term care insurance. 
 
New findings  
Any new important information that is discovered during the study and which may 
influence your willingness to continue participation in the study will be provided to you. 
 
What happens if I say “Yes”, but I change my mind later? 
If you take part in this research study, and want to leave, you should let a member of 
the research staff or your doctor know. Your choice not to be in this study will not 
negatively affect your right to any present or future medical care. If you decide to leave 
the study before the End of Study Treatment visit 4 weeks (28 days) after the FT596 


 
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dose, you are asked to maintain contact with your study doctor in case of side effects. 
Regardless, it will be recommended that you continue the routine post-transplant follow-
up.  
 
If you stop being in the research, information about you that has already been collected 
may not be removed from the study database. 
 
The study doctor or the sponsor can stop your participation at any time without your 
consent for the following reasons: 
• If it appears to be medically harmful to you; 
• If you fail to follow directions for participating in the study; 
• If it is discovered that you do not meet the study requirements; 
• If the study is canceled; or  
• For administrative reasons. 
 
What are the risks of being in this study?  Is there any way being in this study 
could be bad for me? (Detailed Risks) 
You may experience all, some, or none of the side effects described below. If you do 
experience any of them, they may vary in severity. The severity may be mild, moderate, 
or severe, up to and including death. You may experience side effects that are not 
expected and side effects may happen long after you receive FT596. 
 
This is one of the first time that FT596 has been given to people, and therefore the risks 
are not known.   
 
Risks Related to FT596 
• Infusion-related or allergic reaction 
During the FT596 infusion or shortly after there is a risk of an infusion related 
reaction. This reaction may be mild (skin irritation/rash) to life-threatening 
(difficulty breathing/swelling of the face and throat). To lessen the risk of a 
reaction you will receive acetaminophen (Tylenol) and diphenhydramine 
(Benadryl) before and a few hours after the cell infusion. If an infusion reaction 
occurs, you will receive the appropriate medical care. 
• Cytokine release syndrome 
 
Cytokine release syndrome (also called CRS) is an inflammatory response your 
body may experience with therapies designed to stimulate your immune system. 
CRS symptoms are usually mild to moderate, and include: 
o Fever 
o Nausea 
o Chills 
o Decreased blood pressure 
o Increased heart rate 
o Weakness 
o Headache 
o Rash 
o Scratchy throat 


 
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o Difficulty breathing 
 
However, in rare instances, subjects can develop severe, even potentially life-
threatening symptoms of CRS.  
• Loss of engraftment or failure to engraft (blood count recovery after 
transplant) 
It is not known if giving FT596 before blood counts have recovered (engrafted) 
will affect blood count recovery after transplant. This is one of things this study is 
looking at. To be eligible for Component 1 (Day 30 FT596) blood count recovery 
must have occurred. Subjects receiving FT596 around Day 7 after transplant 
(Component 2) blood count recovery is not required.  
• Effects on the nervous system 
Although this has not been a common risk with other NK cell therapies, treatment 
with cell therapies may result in side effects involving the brain and other parts of 
the nervous system. Effects observed with other cell therapies include confusion, 
delirium, and sometimes seizures and swelling of the brain that could lead to 
death. 
• DMSO and albumin related risks 
FT596 is stored in a solution containing dimethyl sulfoxide (DMSO) and human 
albumin. DMSO may cause side effects like: 
o Coughing 
o Flushing 
o Rash 
o Chest tightness 
o Wheezing 
o Nausea 
o Vomiting 
o High or low blood pressure 
 
Because of the small volume of the cell product, a reaction is not expected. You will 
receive intravenous (IV) fluid before and after the FT596 to reduce this risk. 
 
• Allergic reactions may occur with human albumin. Symptoms could include: 
o Fever 
o Chills 
o Rash 
o Nausea 
o Vomiting 
o Fast heart rate 
o Low blood pressure 
• Increased risk of infection 
 
Since FT596 is a cell therapy of human origin, there is a risk that you could 
receive infectious agents such as viruses, and/or other non-infectious agents, 
which may also cause side effects. FT596 has been extensively tested to reduce 
the risk of disease infection. However, these measures do not completely 
eliminate this risk. For some infectious agents, there are no routine tests to 
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• Tumor lysis syndrome  
Tumor lysis syndrome (also called TLS) can happen when cancer cells have 
broken down and pieces of those cells enter the bloodstream. Because of the 
transplant, there should be no or very few cancer cells in your body. TLS is not 
expected in this study. Symptoms may include weakness, low blood pressure, 
muscle cramps, and decreased urination. TLS can lead to kidney damage and/or 
other organ damage. Many factors can contribute to TLS, including the type of 
cancer you have, as well as what kind of treatments you have already had for 
your cancer. Let your study doctor know immediately if you are unable to urinate. 
 
Risks of Rituximab 
The risks of rituximab are well known, although it is not known if they will be different 
when rituximab is given before FT596. The 2-3 day delay between the rituximab and 
FT596 is to ensure there are no ongoing toxicities from the rituximab before giving 
FT596. 
 
You may have received or will receive additional doses of rituximab outside of the single 
dose given in this study. Some of the risks refers to first infusion and others to 2nd or 
later which is based on your personal history of rituximab infusions.  A summary is 
below: 
 
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) 
• allergic reaction with 
second and later 
infusions (same 
symptoms as under 
common)  
• low white blood cell 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 
 
 
 
 


 
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Other study risks may include: 
• Blood Draws: you may feel pain and have minor bruising or bleeding at the 
needle site. There is a small chance of infection, and sometimes people feel faint 
or lightheaded when their blood is drawn. 
• Risks of Genetic Research - The risks to you and your family from genetic 
research on the blood samples are very low, as the testing is on the abnormal 
cells, not your family genetics. The unique subject code assigned at study 
enrollment is used instead of your name or other identifying information making it 
difficult for anyone looking at the sample to know it belongs to you. Testing is 
done in batches (more than 1 subject at a time) and no research results will be 
placed in your medical record. 
• Because this study involves the use of your identifiable, personal information, 
there is a chance that a loss of confidentiality will occur. There are procedures in 
place to lessen the possibility of this happening (see “What happens to the 
information collected for the research, including my health information?” section 
below). 
 
What do I need to know about reproductive health and/or sexual activity if I am in 
this study?   
The effect of FT596 on an unborn baby or on sperm are not known. However, in this 
study all subjects receive rituximab which the effects on conception are better known 
and requires a minimum of 12 months of pregnancy prevention in both women and 
men. 
 
Women who are pregnant are not eligible to take part in this study.  
 
Females: Women of child-bearing potential must use a highly effective form of 
contraception from enrollment until at least 12 months after the final dose of rituximab. 
 
Males: Must be sterile (biologically or surgically) or use a highly effective method of 
contraception from enrollment until at least 12 months after the final dose of rituximab. 
 
According to the World Health Organization and the United States Center for Disease 
Control and Prevention, the most effective forms of birth control include complete 
abstinence, surgical sterilization (both male and female), intrauterine devices (IUDs), 
and the contraceptive implant. The next most effective forms of birth control include 
injectables, oral contraceptive pills, the contraceptive ring, or the contraceptive patch.  
Acceptable, but least effective, methods of birth control include male condoms (with or 
without spermicide) and female condoms. 
 
If you or a female partner of a male subject become pregnant within 4 months after the 
last dose of FT596, it is important that you notify the study doctor or another research 
team member; however, pregnancy must not occur within 12 months after the last dose 
rituximab. 
 


 
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Will it cost me anything to participate in this research study? 
FT596 is provided at no cost by Fate Therapeutics for the purpose of this study. The 
cost of processing and testing any samples collected for research is paid for by study 
funds. 
 
Rituximab is also is known by its brand names of Rituxan, Truxima, and Ruxience. 
Rituxan was the original biologic form of rituximab to receive FDA approval. Truxima 
and Ruxience are FDA approved biosimilars. Drugs have generic versions, biologics 
have biosimilars. Biosimilars are made from the same types of natural sources, given in 
the same way, have the same treatment benefits, and same potential side effects. A 
prior authorization will be obtained from your health insurance for rituximab. Often, an 
insurance only will approve a biosimilar version as generally it is less expensive. This 
study permits use of whichever version of rituximab your health insurance approves.   
 
You and/or your insurance company will be billed for any standard medical care given 
during this research study. This means your insurance company will be billed for the 
rituximab, hospitalization, outpatient clinic visits, routine medical care, all lab tests done 
for standard safety assessment, and assessments that are done for your medical care. 
You will be responsible for any copays your insurance normally issues for these 
visits/procedures. 
 
Compensation For Participation  
You will not receive any monetary compensation for your participation in this study. 
 
What happens to the information collected for the research, including 
my health information? 
The researchers will do their best to make sure that your private information 
is kept confidential. Information about you will be handled as confidentially as 
possible but participating in research may involve a loss of privacy and has a 
potential for breach of confidentiality. Study data will be physically and 
electronically secured. As with any use of electronic means to store data, 
there is a risk of breach of data security. 
 
Overview 
If you participate in this study, your information, including your health 
information, will be used and shared for purposes of conducting this 
research. As described later in this Consent Form, your information may 
also be used and shared for publishing and presenting the research results, 
future research. If you sign and date this Consent Form, you are giving 
permission to use and share your health information for these purposes 


 
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and you are giving permission to any health care providers who are treating 
you to share your medical records with us.   
 
What health information will be made available? 
Health information about you to be used and shared for the research 
includes those items checked by the research team below: 
 
☒ Your medical records, which may include records from hospital and clinic 
visits, emergency room visits, immunizations, medical history and physical 
exams, medications, images and imaging reports, progress notes, 
psychological tests, electroencephalography (EEG), electrocardiogram 
(ECG), and echocardiogram ECHO reports, lab and pathology reports, 
dental records and/or financial records.  These records may be used and 
shared for as long as this research continues. 
 
☒ Information collected as part of this research study, including research 
procedures, research visits, and any optional elements of the research you 
agree to, all as described in this Consent Form.  This information might not 
be part of your medical record, and may include things like responses to 
surveys and questionnaires, and information collected during research 
visits described in this Consent Form. 
 
What about more sensitive health information? 
Some health information is so sensitive that it requires your specific 
permission.  If this research study requires any of this sensitive information, 
the boxes below will be marked and you will be asked to initial to permit this 
information to be made available to the research team to use and share as 
described in this Consent Form. 
☐ My drug & alcohol abuse, diagnosis & treatment records ______ 
(initial) 
☒ My HIV/AIDS testing records  ______ (initial) 
☒ My genetic testing records  ______ (initial) 
☐ My mental health diagnosis/treatment records  ____ (initial) 
☐ My sickle cell anemia records  _______ (initial) 
 
Who will access and use my health information? 
If you agree to participate in this study, your information will be shared with: 
• The University of Minnesota research team and any institutions or 
individuals collaborating on the research with us; 


 
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• Others at the University of Minnesota and M Health/Fairview who 
provide support for the research or who oversee research (such as 
the Institutional Review Board or IRB which is the committee that 
provides ethical and regulatory oversight of research at the 
University, systems administrators and other technical and/or 
administrative support personnel, compliance and audit professionals 
(Such as the Quality Assurance Program of the Human Research 
Protection Program (HRPP)), individuals involved in processing any 
compensation you may receive for your participation, and others); 
• The research sponsor(s), any affiliates, partners or agents of the 
sponsor(s) involved in the research, organizations funding the 
research, and any affiliates, partners or agents of the funding 
organization(s) involved in the research; 
• Organizations who provide accreditation and oversight for research 
and the research team, and others authorized by law to review the 
quality and safety of the research (such as U.S. government agencies 
like the Food and Drug Administration, the Office of Human Research 
Protections, the Office of Research Integrity, or government agencies 
in other countries); and 
• Advarra IRB, the independent external Institutional Review Board that 
is responsible for the review of this study. 
 
How will my information be used in publications and presentations? 
Your health data will be used to conduct and oversee the research. We 
may publish the results of this research in scientific, medical, academic or 
other journals or reports, or present the results at conferences.  Information 
that makes it easy to identify you (such as your name and contact 
information, social security number (SSN) and medical records number) will 
not be part of any publication or presentation.  If you have an extremely 
unique or rare condition that is not shared by many others, it is possible 
that some people may be able to determine your identity even without 
these identifiers. 
 
Optional Consent for Future Use of Identifiable Data or Specimens 
At the completion of this research study, we would like to store and be able 
to use and share your identifiable research related samples and/or health 
information with researchers at the study site or affiliated hospitals for other 
research related to the immune system and/or cancer.  Any research that 
involves identifiable information will be reviewed by an Institutional Review 
Board (IRB), which is the committee that provides ethical and regulatory 


 
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oversight of research, prior to use. Because these specimens and/or health 
information are identifiable, we are asking your permission to store, use 
and share these for other research.  
 
We may not ask for your consent before using or sharing your identifiable 
specimens or data. You will not receive any results or financial benefit from 
the future research done on your specimens or data.  We may share your 
identifiable specimens or data with outside researchers who will use them 
for future research. Samples are labelled with your unique study code 
assigned at study enrollment and information such as the date of 
collection/study day that can be linked back to your health information 
through a master study list.  
 
If you leave the study, you can ask to have the data collected about you 
removed or the samples destroyed. You can also ask us to remove 
information that identifies you from the data or samples. This may not be 
possible if your samples and data have already been shared. 
 
Please indicate whether you will allow the identifiable research related 
samples and/or health information to be used for future research by putting 
your initials next to one of the following choices: 
 
_____ (initials)  NO, my identifiable research related samples and/or 
health information may not be used for future research. 
They may be used for this study only. 
_____ (initials)  YES, my identifiable research related samples and/or 
health information may be used for other future 
research studies 
 
Do I have to sign and date this authorization and give my permission 
to make my information, including my health information, available for 
use and sharing? 
No, you do not have to sign and date this authorization. But if you do not 
sign and date it, you will not be able to participate in this research study. 
Treatment available outside of the study, payment for such treatment, 
enrollment in health insurance plans and eligibility for benefits will not be 
impacted by your decision about signing and dating this authorization. 
 


 
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Does my permission for making my health information available for 
use and sharing ever expire? 
No, there is no expiration date. In California and any other state that 
requires an expiration date, the Authorization will expire 50 years after you 
sign and date this authorization document. 
 
May I cancel my permission for making my health information 
available for use and sharing? 
Yes.  You may cancel your permission at any time by writing to the study 
doctor at the address on the first page of this form. If you cancel your 
permission, you will no longer be in the research study. You may also want 
to ask someone on the research team in canceling will affect any research 
related treatment. If you cancel your permission, any health information 
about you that was already used and shared may continue to be used and 
shared for the research study and any optional elements of the study to 
which you agree in this authorization. 
 
What happens to my health information after it is shared with others? 
When we share your information with others as described in this 
authorization, privacy laws may no longer protect your information and 
there may be further sharing of your information. 
 
Will I be able to look at my records? 
It is possible that the research team may not allow you to see the 
information collected for this study. However, you may access any 
information placed in your medical records after the study is complete. 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
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STATEMENT OF AUTHORIZATION 
I have read this form and its contents were explained. My questions have 
been answered. I voluntarily agree to allow study staff to collect, use and 
share my health data as specified in this form. I will receive a signed and 
dated copy of this form for my records. I am not giving up any of my legal 
rights by signing and dating this form.  
 
__________________________________________      _______________ 
Signature of Subject                                                          Date 
 
__________________________________________ 
Printed Name of Subject 
 
 
 


 
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Veronika Bachanova , MD, PhD 
Advarra IRB Approved Version 14 Dec 2020 
Revised 14 Dec 2020 
 
WITNESS SIGNATURE FOR SUBJECTS WHO CANNOT READ  
The study subject has indicated that he/she is unable to read. This 
Authorization document has been read to the subject by a member of the 
study staff, discussed with the subject by a member of the study staff, and 
the subject has been given an opportunity to ask questions of the study 
staff.   
 
 
____________________________________ 
Printed Name of Impartial Witness  
 
 
____________________________________  
 
__________ 
Signature of Impartial Witness  
 
 
 
Date 
 
What will be done with my data and specimens when this study is over? 
We will use and may share data and/or specimens for future research. They may be 
shared with researchers/institutions outside of the study site. This could include for profit 
companies. We will not ask for your consent before using or sharing them. We will 
remove identifiers from your data and/or specimens, which means that nobody who 
works with them for future research will know who you are. Therefore, you will not 
receive any results or financial benefit from future research done on your specimens or 
data. No results from research related testing will be placed in your medical record. 
 
Research samples may be sent to an outside laboratory for testing (including to Fate 
Therapeutics) that cannot be routinely performed at the study site. No information to 
directly identify you will be provided on these samples. 
 
Will I receive research test results? 
No, individual tests results will not be shared with subjects. Research related testing is 
not done in real-time like lab work for medical care. Instead the samples are stored 
frozen and tested in batches at a future date.  If the research with your identifiable 
information or samples gives results that do have meaning for your health, the 
investigators will contact you to let you know what they have found.   
 
Whom to contact about this study 
During the study, if you experience any medical problems, suffer a research-related 
injury, or have questions, concerns or complaints about the study, please contact the 
study doctor at the telephone number listed on the first page of this consent document. 
If you seek emergency care, or hospitalization is required, alert the treating physician 
that you are participating in this research study. 
 


 
Veronika Bachanova, MD - University of Minnesota / Protocol Number 2019LS230 (MT2019-46) 
Page 21 of 23   
 
Veronika Bachanova , MD, PhD 
Advarra IRB Approved Version 14 Dec 2020 
Revised 14 Dec 2020 
 
An institutional review board (IRB) is an independent committee established to help 
protect the rights of research subjects. If you have any questions about your rights as a 
research subject, and/or concerns or complaints regarding this research study, contact: 
 
• By mail:  
Study Subject Adviser 
Advarra IRB 
6940 Columbia Gateway Drive, Suite 110 
Columbia, MD 21046 
• or call toll free:        877-992-4724 
• or by email:              adviser@advarra.com 
 
Please reference the number when contacting the Study Subject Adviser: Pro00045966. 
 
To share feedback privately with the University of Minnesota Human Research 
Protection Program (HRPP) about your research experience, call the Research 
Participants’ Advocate Line at 612-625-1650 or go to 
https://research.umn.edu/units/hrpp/research-participants/questions-concerns  . You are 
encouraged to contact the HRPP if:  
 
• Your questions, concerns, or complaints are not being answered by the research 
team. 
• You cannot reach the research team. 
• You want to talk to someone besides the research team. 
• You have questions about your rights as a research participant. 
• You want to get information or provide input about this research. 
 
The University of Minnesota HRPP may ask you to complete a survey that asks about 
your experience as a research participant. You do not have to complete the survey if 
you do not want to. If you do choose to complete the survey, your responses will be 
anonymous.  If you are not asked to complete a survey, but you would like to share 
feedback, please contact the study team or the University of Minnesota HRPP. 
 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov. This 
Web site will not include information that can identify you. At most, the Web site will 
include a summary of the results. You may search this Web site at any time. 
 
Will I have a chance to provide feedback after the study is over? 
You may be asked to complete a survey that asks about your experience as a research 
subject. You do not have to complete the survey if you do not want to. If you do choose 
to complete the survey, your responses will be anonymous.   
 
If you are not asked to complete a survey, but you would like to share feedback, please 
contact the study team at the contact information located on page 1 of this form. 
 


 
Veronika Bachanova, MD - University of Minnesota / Protocol Number 2019LS230 (MT2019-46) 
Page 22 of 23   
 
Veronika Bachanova , MD, PhD 
Advarra IRB Approved Version 14 Dec 2020 
Revised 14 Dec 2020 
 
What happens if I am injured while participating in this research? 
In the event that this research activity results in an injury, treatment will be available, 
including first aid, emergency treatment and follow-up care as needed.  Care for such 
injuries will be billed in the ordinary manner, to you or your insurance company.  If you 
think that you have suffered a research related injury, let the study staff know right 
away. By signing and dating this document, you will not lose any of your legal rights or 
release anyone involved in the research from responsibility for mistakes.  
 
Optional Storing of Leftover Samples for Future Research: 
Once the research associated with this study there may be some leftover blood and 
cells from the samples collected for research purposes. With your permission we would 
like to store them for up to 15 years after the study ends for future analysis as new 
things are learned about the immune system and cancer. Leftover samples may be sent 
to labs outside of the study site if specialized testing cannot be performed locally. There 
is no cost to you or your insurance company for long-term storage. If you agree to 
storage now and later change your mind, you may contact a member of the study team 
and request that any remaining identifiable samples be destroyed. 
 
Use of Identifiable Research Related Samples and/or Health Information  
Please indicate whether you will allow the identifiable research related samples and/or 
health information to be used for future research by putting your initials next to one of 
the following choices as you indicated on page 17 of this document: 
 
_____ (initials)  NO, my identifiable research related samples and/or health 
information may not be used for future research. They may be 
used for this study only. 
_____ (initials)  YES, my identifiable research related samples and/or health 
information may be used for other future research studies 
 
Signature Block for Capable Adult: 
 
Your signature documents your permission to take part in this research. You will be 
provided with a copy of this signed and dated document. 
 
_______________________________________________      __________________ 
Signature of Subject                                                                    Date 
 
_______________________________________________ 
Printed Name of Subject 
 
____________________________________________            __________________ 
Signature of Person Obtaining Consent                                       Date 
 
______________________________________________________ 
Printed Name of Person Obtaining Consent 
 


 
Veronika Bachanova, MD - University of Minnesota / Protocol Number 2019LS230 (MT2019-46) 
Page 23 of 23   
 
Veronika Bachanova , MD, PhD 
Advarra IRB Approved Version 14 Dec 2020 
Revised 14 Dec 2020 
 
WITNESS SIGNATURE FOR SUBJECTS WHO CANNOT READ  
The study subject has indicated that he/she is unable to read. The consent document 
has been read to the subject by a member of the study staff, discussed with the subject 
by a member of the study staff, and the subject has been given an opportunity to ask 
questions of the study staff.   
 
 
________________________________________ 
Printed Name of Impartial Witness  
 
 
________________________________________ 
 
___________ 
Signature of Impartial Witness 
 
 
 
Date