Clinical trial NCT04714372
Conditions: Acute Myeloid Leukemia Myeloid Leukemia Monocytic Leukemia
Keywords: FT538, AML, Daratumumab, CD38
Sponsor: Masonic Cancer Center, University of Minnesota
Start date: 2021-11-03; Completion date: 2024-10-15
Enrollment: 9 participants; Allocation: NON_RANDOMIZED; Intervention model: SEQUENTIAL

Brief summary:
This Phase I open-label dose escalation study is conducted in two stages with a primary endpoint to identify the maximum tolerated dose (MTD) of FT538 when administered with daratumumab in patients 12 years and older with advanced acute myeloid leukemia (AML) and related myeloid diseases.

Detailed description:
FT538 is an off the shelf product comprised of allogeneic natural killer (NK)-cell immunotherapy lacking CD38 and expressing hnCD16 and IL-15RF. Daratumumab is a targeted therapy (IgG1k human monoclonal antibody) that targets CD38.

FT538 is administered once a week for 3 consecutive weeks (Day 1, Day 8, and Day 15). Up to 5 dose levels will be tested. Fixed dose subcutaneous daratumumab is given on Day -12 and Day 5 prior to the NK cells as lymphodepletion, and on Day +3, Day +10, and Day +17 to maximize targeting. A short course of outpatient lymphodepleting chemotherapy is given on Day -4 and Day -3 to promote adoptive transfer. Day 1, the day of the 1st FT538 infusion, must be a Monday.

The primary analysis for Phase I is intent-to-treat in that all patients receiving the 1st infusion of FT538 are evaluable for toxicity and efficacy. Patients who discontinue therapy prior to the first FT538 will be replaced.

There are five potential FT538 dose cohorts. The starting dose is FT538 1x10e8 cells per dose with a lower safety dose of 5x10e7 if needed (Dose Level -1). The subsequent planned FT538 cohorts are 3x10e8, 1x10e9, and 1.5 x10e9 FT538 cells per dose. Dosing is based on hnCD16 expression, where 90% ± 10% of administered FT538 cells express hnCD16. The trial is conducted with no intra-patient escalation.

Arms: arm 1: FT538 administered at assigned dose as an IV infusion via gravity on Day 1, Day 8, and Day 15 arm 2: FT538 administered at assigned dose as an IV infusion via gravity on Day 1, Day 8, and Day 15 arm 3: FT538 administered at assigned dose as an IV infusion via gravity on Day 1, Day 8, and Day 15 arm 4: FT538 administered at assigned dose as an IV infusion via gravity on Day 1, Day 8, and Day 15
Interventions: intervention 1: Daratumumab/rHuPH20 intervention 2: FT538 intervention 3: Fludarabine intervention 4: Cyclophosphamide
Intervention descriptions: intervention 1: Daratumumab 1800 mg co-formulated with 30,000 units of hyaluronidase (rHuPH20) given subcutaneously into subcutaneous tissue of the abdomen approximately 3 inches \[7.5 cm\] to the right or left of the navel over approximately 3-5 minutes on Day -12 and Day -5 prior to the 1st FT538 infusion, and on Day +3, Day+10, and Day+17 approximately 48 hours after each FT538 infusion. intervention 2: FT538 is administered as an IV infusion via gravity using an IV administration set with an in-line filter at the patient's assigned dose levels (DL) on Day 1, Day 8, and Day 15 intervention 3: Fludarabine 25 mg/m\^2 is administered as a 1 hour intravenous (IV) infusion per institutional guidelines once a day on 2 consecutive days (Day -4, and Day -3). intervention 4: Cyclophosphamide 300 mg/m\^2 is administered as a 2 hour intravenous (IV) infusion per institutional guidelines once a day on the same days that fludarabine is given.

Protocol documents:
Prot_SAP_000.pdf: 
 
 
Masonic Cancer Center, University of Minnesota 
Cancer Experimental Therapeutics Initiative (CETI) 
 
 
Study of FT538 in Combination with Daratumumab in  
Acute Myeloid Leukemia 
CPRC #2020LS114 
MT2020-33 
IND # 26974 
 
Principal Investigator/IND Sponsor: 
Joseph Maakaron, MD 
Division of Hematology/Oncology/Transplantation 
Medicine Hematology Office 
420 Delaware Street SE MMC 480  
Minneapolis, MN 55455 
Phone: 612-625-8942 (Administrative phone) 
Email: maaka001@umn.edu 
 
 
Collaborators: 
Daniel Weisdorf, MD 
Margaret L. Macmillan, MD (pediatrics) 
Jeffrey S. Miller, MD* 
David H. McKenna, Jr., MD* 
*Will not consent patients to enroll on study 
 
 
Biostatistician: 
Ryan Shanley, MS 
University of Minnesota 
 
 
Version Date: 
May 8, 2023 
 
 
Confidential 


CPRC #2020LS114:  FT538 with Daratumumab in Acute Myeloid Leukemia 
 
 
 
 
 
 
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Revision History 
Revision 
# 
Version Date 
Revision Details 
Consent 
Revision 
 
Oct 28, 2020 
Original to FDA 
n/a 
 
Dec 7 2020 
Original to CPRC 
Synopsis, Section 3, Section 4, and Section 7: In response to 
the clinical IR dated Nov 27 2020 – Delay pediatric enrollment 
until a minimum of 6 adults are treated on this study and/or the 
combination arm on Fate’s FT538-101 and safety data is 
submitted to the FDA for their review and permission to 
proceed with the enrollment of children is received. 
Minor edits and clarifications in Section 8 and Section 10. 
n/a 
 
Jan 27 2021 
In response to CPRC stipulations – updates to Section 12 and 
other relevant protocol sections (increasing expected 
enrollment to 17 from 15 patients). 
Updates from CCPM: 
• Schema: delete Day +24 under description of DARA 
administration plan as artifact previously missed. 
• Synopsis, Schema, Section 3, Section 5: Correct intra cohort 
enrollment plan from no staggering required to “A minimum 
of 14 days must pass between the enrollment of the 1st and 
the 2nd patient in 3 patient cohorts.” to match language in 
Section 12. 
• Synopsis, Section 4.1: prior allogenic HSCT permitted but 
remove reference to relapse  
• Synopsis, Section 4.3.13: remove relapse contingency for 
exclusion for allogeneic HSCT within previous 90 days 
Other general updates: 
• update protocol that DARA will be purchased for the study,  
• delete reference of Monday as 1st day of FT538 through-out 
while retaining Monday as Day 1 on an example calendar in 
Section 6. 
• update LTFU study number to CPRC 2020LS220, remove 
the “0” from the MT number to read MT2020-33 
• update Section 3 study design for clarity, correct Section 
numbers for DLT and SRs 
• other minor edits/updates throughout 
n/a 
1 
Mar 11 2022 
• Section 6 introduction and Section 6.4 - permit the use of 
hydroxyurea during study treatment as needed for the control 
of peripheral blood blasts and/or white blood count. 
• Update title page to reflect Dr. Maakaron also is the IND 
sponsor and change in statistician, delete Key Study Staff 
Contact Information on page 2 as no longer needed.  
• Section 11.3 – list Dr. Maakaron as the IND S/I, add Dr. 
MacMillan as pediatric physician. 
Minor changes/edits identified during and since the study 
initiation visit (SIV) in Aug 2021:  
• Update abbreviation table with SUSAR and S/I 
simplify 
FT538 
enrollment 
plan and 
clean-up 


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Revision 
# 
Version Date 
Revision Details 
Consent 
Revision 
• Schema, Section 3 -Simplify how enrollment plan is written 
without change to content. 
• Synopsis, Section 4.2.3 – update KPS/Lansky lower eligibility 
limit from ≥80 to ≥70 (from SIV) 
• Synopsis, Section 4.2.4 – clarify lab work is done within 14 
days prior to start of study treatment, delete cardiac 
requirement as addressed in exclusion criteria Section 4.3.4. 
• Section 6.1 – clarify monitoring section for daratumumab 
• Section 6.5 - expand duration of treatment section to include 
end of treatment assessment with reminder stopping rules 
monitoring is through Day 42. 
• Section 6.6 - clarify follow-up for disease response/survival  
• Section 8 – clarify the timing of the end of DLT/EOT 
assessment as both are scheduled for Day 29 
• Section 8.1 – eliminate ICANS assessment at screening and 
Day -5 as neuro changes are associated with FT538 
• Section 8.2 – add yellow top tube baseline safety samples for 
Fate in the event a patient had previously received a Fate 
product that used a lentivirus vector in manufacturing 
• Section 10.1 – remove the definition of protocol deviation as 
defined only applicable to studies covered by UMN IRB  
• Section 10.2 – clarify any event meeting the definition of 
serious must be recorded as an AE, clarify the reporting of 
abnormal lab values and assessments 
• Appendix III – CY/FLU adverse events – replace section 
wording to match Fate Therapeutics’ sponsored trials 
• Through-out the protocol delete the CPRC number for the 
LTFU protocol as being replaced by a master LTFU protocol 
• Other minor edits/clarifications 
 
Nov 24 2022 
Rationale for current amendment: please see section 2.5, 
bottom of page 18.  
• Synopsis, schema, section 2.5, section 6.2- Update to 
lymphodepletion fludarabine days given (-6 to -2) and 
cyclophosphamide dosing (changed from 300mg/m2 to 60 
mg/kg), spacing between subjects in final cohort 
• Section 3 – updates to fast-track cohort spacing between 
subjects in expansion  
• Section 6 – updated table in treatment plan to reflect updated 
LD 
• Section 6.3.1 – minor clarification to DLT events 
• Section 7 - minor clarification to ensure proper classification 
of febrile neutropenia events per protocol 
• Section 8.1 – updated clinical Schedule of Treatments to 
reflect day -6 and day -2 
• Section 8.2 – updated Research Related Tests and 
Procedures to include bone marrow biopsy at day +3 (±1 
day) 
• Section 12.1-updated fast-track cohort spacing in statistics 
section to reflect changes in section 3 
 


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Revision 
# 
Version Date 
Revision Details 
Consent 
Revision 
 
03/23/2023 
Synopsis, schema, section 6.1 – revised to reflect that 
daratumumab reduced to one dose from four 
Section 2.5 – revised to address reduction in daratumumab 
Section 4.2.5 – revised to update contraceptive use guidelines 
Section 8.1 and 8.2 – revised to remove days 10 and 17 to 
reflect updated treatment schedule/adjust research blood 
draws accordingly 
Appendix VI: added to document previous study schema 
Minor corrections of typos/formatting throughout 
Consent: revised to include language re: risk of 
xenotransplantation required by FDA 
Y 
 
04/20/2023 
Section 12.1: fixed typo in paragraph 3, dose level 3 is 1x109 
cells 
Appendix V and VI: per CPRC recommendation updated titles 
with more information re: previous versions 
n 
 
05/08/2023 
Corrected typo in section 12.1 per CPRC request. 
n 


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TABLE OF CONTENTS 
 
Key Abbreviations .................................................................................................................... 7 
Protocol Synopsis .................................................................................................................... 8 
Study Schema........................................................................................................................ 12 
1 
Objectives ....................................................................................................................... 14 
1.1 Primary Objective .................................................................................................... 14 
1.2 Secondary Objectives .............................................................................................. 14 
1.3 Correlative Objectives ............................................................................................. 14 
2 
Background and Significance .......................................................................................... 14 
2.1 Introduction and Disease Under Treatment ............................................................. 14 
2.2 Natural Killer Cells ................................................................................................... 15 
2.3 FT538 ...................................................................................................................... 17 
2.4 The Role of Daratumumab and Use of subQ DARZALEX FASPRO ........................ 18 
2.5 Lymphodepletion with Cyclophosphamide and Fludarabine .................................... 19 
2.6 Study Rationale ....................................................................................................... 20 
2.7 Rationale to Include Pediatric Patients 12 Years Old or Older ................................. 20 
3 
Study Design .................................................................................................................. 21 
4 
Patient Selection ............................................................................................................. 24 
4.1 Disease Specific Inclusion Criteria ........................................................................... 24 
4.2 Inclusion Criteria ...................................................................................................... 24 
4.3 Exclusion Criteria .................................................................................................... 25 
5 
Patient Screening and Enrollment ................................................................................... 26 
5.1 Registration with the Masonic Cancer Center Clinical Trials Office .......................... 26 
5.2 Patient Enrollment and Dose Cohort Placement ...................................................... 26 
5.3 Patients Who Do Not Begin Study Treatment .......................................................... 26 
6 
Treatment Plan ............................................................................................................... 27 
6.1 Daratumumab Administration Guidelines ................................................................. 27 
6.2 Cyclophosphamide/Fludarabine Lymphodepletion Guidelines ................................. 29 
6.3 FT538 Administration .............................................................................................. 29 
6.4 Permitted and Prohibited Concomitant Medications/Therapies ................................ 32 
6.5 Duration of Treatment .............................................................................................. 33 
6.6 Follow-Up for Disease Response and Survival (Duration of Study Participation) ..... 33 
6.7 Continuation of Follow-Up via a Separate Long-Term Follow-Up Protocol ............... 34 
7 
Recommended Management Guidelines for Specific Adverse Events Associated with 
FT538 .................................................................................................................................... 34 
7.1 Infusion Related Reaction Associated with FT538 ................................................... 36 
7.2 DMSO Related Risks ............................................................................................... 37 
7.3 Infection ................................................................................................................... 37 
7.4 Cytokine Release Syndrome (CRS) or CRS-Like Symptoms ................................... 38 
7.5 Neurotoxicity............................................................................................................ 40 
7.6 Acute Graft-versus-Host Disease ............................................................................ 44 
7.7 Tumor Lysis Syndrome (TLS) .................................................................................. 45 
7.8 Myelosuppression, Immunosuppression, Bone Marrow Failure, and Infections ....... 46 
7.9 Immunogenicity ....................................................................................................... 46 


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8 
Schedule of Treatment, Tests, and Procedures .............................................................. 47 
8.1 Required Clinical Care Evaluations ......................................................................... 48 
8.2 Research Related Tests and Procedures ................................................................ 50 
9 
Study Agents .................................................................................................................. 51 
9.1 FT538 ...................................................................................................................... 51 
9.2 Daratumumab .......................................................................................................... 52 
10 Adverse Event Monitoring, Documentation, and Reporting ............................................. 55 
10.1 Adverse Event Terminology ..................................................................................... 56 
10.2 AE Monitoring and Event Documentation Requirements ......................................... 57 
10.3 SAE Documentation and Reporting ......................................................................... 59 
10.4 Dose Limiting Toxicity and Excessive Toxicity (Stopping Rule Events) Documentation 
and Reporting Requirements ........................................................................................... 59 
10.5 Documentation of Death and Reporting Requirements ............................................ 59 
10.6 Expedited MCC Reporting Requirements ................................................................ 60 
11 Study Data Collection and Monitoring ............................................................................. 60 
11.1 Data Management ................................................................................................... 60 
11.2 Case Report Forms ................................................................................................. 61 
11.3 Data and Safety Monitoring Plan (DSMP) ................................................................ 61 
11.4 Site Monitoring ........................................................................................................ 62 
11.5 Record Retention .................................................................................................... 62 
12 Statistical Considerations ................................................................................................ 62 
12.1 Study Design, Objectives and Endpoints ................................................................. 62 
12.2 Statistical Analysis ................................................................................................... 64 
12.3 Sample Size ............................................................................................................ 64 
12.4 Monitoring Guidelines (Early Study Stopping Rules) ................................................ 65 
13 Conduct of the Study ...................................................................................................... 66 
13.1 Good Clinical Practice ............................................................................................. 66 
13.2 Ethical Considerations ............................................................................................. 66 
14 References ..................................................................................................................... 67 
Appendix I – Karnofsky Performance Status Scale/Lansky Play–Performance Scale ............ 70 
Appendix II – New York Heart Association (NYHA) Classification .......................................... 72 
Appendix III - Risks Associated with Cyclophosphamide and Fludarabine ............................. 73 
Appendix IV – European LeukemiaNet (ELN) Response Criteria in Acute Myelogenous 
Leukemia ............................................................................................................................... 75 
 
 


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Key Abbreviations 
Abbreviation 
Definition 
ABW 
actual body weight 
ADL 
activities of daily living 
AE 
adverse event 
AML 
acute myelogenous leukemia 
CFR 
Code of Federal Regulations 
CNS 
central nervous system 
CR 
complete remission 
CRi 
complete remission with incomplete count recovery 
CRM 
continuous reassessment method 
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 
ELN 
The European LeukemiaNet 
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 
ICANS 
immune cell associated neurotoxicity syndrome 
ICH 
International Conference on Harmonization 
rHuPH20 
recombinant human hyaluronidase PH20 
IL-15RF 
IL-15 receptor alpha fusion protein 
IND 
Investigational New Drug 
IRB 
Institutional Review Board 
IV 
intravenous 
LTFU 
long-term follow-up 
MLFS 
Morphological Leukemia Free State 
MTD 
maximum tolerated dose 
NCI 
National Cancer Institute 
NK 
natural killer 
OS 
overall survival 
PBMC 
peripheral blood mononuclear cell 
PD 
progressive disease 
PFS 
progression free survival 
PFT 
pulmonary function test 
RECISTv5 
Response Evaluation Criteria in Solid Tumors version 5 
rhIL-15 
Recombinant human interleukin-15 
SAE 
serious adverse event 
S/I 
Sponsor/Investigator 
SOC 
standard of care 
SR 
stopping rule 
subQ 
subcutaneous 
SUSAR 
Suspected Unexpected Serious Adverse Reaction 
TRM 
treatment related mortality 
ULN 
upper limit of normal 
 


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Protocol Synopsis 
Study of FT538 in Combination with Daratumumab in Acute Myeloid Leukemia 
CPRC #2020LS114 / MT2020-33 
Study Design: 
This Phase I open-label dose escalation study is conducted in two stages with a primary endpoint to 
identify the maximum tolerated dose (MTD) of FT538 when administered with daratumumab in patients 
12 years of age and older with advanced acute myeloid leukemia (AML) and related myeloid diseases.  
FT538 is an off-the-shelf product comprised of allogeneic natural killer (NK) cell immunotherapy lacking 
CD38 and expressing hnCD16 and IL-15RF. Daratumumab is a targeted therapy (IgG1k human 
monoclonal antibody) that targets CD38. 
FT538 is administered once a week for 3 consecutive weeks (Day 1, Day 8, and Day 15). Up to 5 dose 
levels will be tested. Fixed dose subcutaneous daratumumab is given on Day -5 prior to the NK cells as 
lymphodepletion. A course of outpatient lymphodepleting chemotherapy is given from Day -6 to Day -2 
to promote adoptive transfer.  
The primary analysis for Phase I is intent-to-treat in that all patients receiving the 1st infusion of FT538 
are evaluable for toxicity and efficacy. Patients who discontinue therapy prior to the first FT538 will be 
replaced.  
All patients are monitored for dose limiting toxicity and early stopping rule events as part of the event 
assessment. Patients are followed for 1 year from the 1st FT538 cell infusion to determine disease free 
survival, treatment related mortality, and time to and incidence of relapse.  
Enrollment 
Plan: 
There are five potential FT538 Dose Levels (DL). The starting dose is FT538 1x108 cells per dose with a 
lower safety dose of 5x107 if needed (Dose Level -1). The subsequent planned FT538 cohorts are 
3x108, 1x109, and 1.5 x109 FT538 cells per dose. The trial is conducted with no intra-patient escalation.  
 
STAGE 1 STEP 1 Fast-track design (1 patient per dose cohort) 
Start at Dose Level 1 (DL1), enroll 1 patient per dose cohort separated by 28 days (DLT period) until 
the:  
• 1st pre-defined adverse event defined as any Grade 3 non-hematologic AE within 72 hours of a 
FT538 infusion  
• and the patient completes the 28 day DLT period with no DLT- Activate Stage 1 Step 2 
OR  
• 1st DLT event within 28 days after the 1st dose of FT538 as defined in the Schema and in Section 
6.3.1 - Activate Stage 2 (Stage 1 Step 2 is not used)  
OR 
• 10 patients are treated at the Dose Level 4 (This completes enrollment - Stage 1 Step 2 and Stage 
2 are not used) 
o 
If the first patient at dose level 4 in stage 1 step 1 completes DLT period with no pre-
defined adverse events or DLT, successive subjects may enroll without staggering.  For 
Dose Level 4, if no pre-defined adverse events or DLT events occur within monitoring 
period for the first patient, subsequent 9 subjects may enroll without staggering 
 
STAGE 1 STEP 2 Expand current Dose Level and subsequent DLs to 3 patients 
The cohort size increases from 1 to 3 patients to explore the occurrence of an AE. Two additional 
patients added to the current cohort without staggering. Continue dose escalation until: 
• 1st DLT event as defined in the Schema and Section 6.3.1 - Activate Stage 2 
OR  
• 10 patients are treated at the Dose Level 4 (This completes enrollment and Stage 2 is not used.) 
o 
For Dose Level 4 in stage 1, step 2, second and third patients may enroll immediately 
but must complete their DLT period prior to enrolling the rest. If no DLT events within 
monitoring period, successive subjects may enroll without staggering  
 
STAGE 2 Continual Reassessment Method (CRM) at the 1st DLT 


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The study design changes to the CRM. Enrollment occurs in cohorts of three. A minimum of 14 days 
must pass between the enrollment of the 1st and the 2nd patient in 3- patient cohorts. Each new cohort of 
three patients is sequentially assigned to the most appropriate dose by the study statistician based on 
the updated toxicity probabilities once the 3rd patient in a cohort reaches Day 29 (end of DLT period). 
The MTD is identified by the minimum of the following criteria: (1) the total Stage 2 maximum sample 
size of 25 is exhausted or (2) 10 consecutive patients are enrolled at the same FT538 dose.  
Investigational 
Products: 
Fate FT538  
Daratumumab and hyaluronidase-fihj (DARZALEX FASPRO™) for subcutaneous administration  
Long-Term 
Follow-up: 
As FT538 is an engineered cellular product long-term follow-up (LTFU) is recommended by the FDA for 
any patient receiving at least one dose of FT538. Clinical safety information is collected at post-
treatment follow-up visits or through telephone calls, medical record review, and/or e-mail/mail for up to 
15 years as described in the companion LTFU protocol. Consent to LTFU is required for participation in 
this treatment study. 
Study 
Rationale: 
FT538 is an allogeneic natural killer (NK)-cell immunotherapy produced from a clonal master human-
induced pluripotent stem cell (iPSC) line with the following engineered elements: a) deletion of the gene 
encoding CD38 (i.e., CD38 knockout to overcome killing of the infused FT538 product by 
daratumumab); b) high-affinity, non-cleavable CD16 receptor (hnCD16) to bind daratumumab; and c) 
interleukin (IL)-15/IL-15 receptor alpha fusion protein (IL-15RF) to enhance survival and activity of NK 
cells after adoptive transfer. The engineered features of FT538 are designed to result in increased 
activity against target tumor cells as monotherapy and when combined with monoclonal antibodies 
(mAbs) that can mediate antibody-dependent cellular cytotoxicity (ADCC). Daratumumab is a targeted 
therapy (IgG1k human monoclonal antibody) that targets CD38.  While daratumumab is FDA approved 
for treatment of multiple myeloma, it is not approved for AML. However, a majority of AML blasts 
express CD38 and daratumumab can mediate antibody dependent cellular cytotoxicity by NK cells. 
Primary 
Objective 
To determine the maximum tolerated dose (MTD) of FT538 when given in combination with 
daratumumab in the treatment of acute myeloid leukemia. 
Secondary 
Objectives: 
• 
To obtain preliminary estimates of efficacy as measured by the objective response (CR + CRi) 
assessed by Day 28, the primary trial endpoint based on the 2017 European LeukemiaNet (ELN) 
response criteria (Döhner 2017)  
• 
Estimate the overall response rate (ORR) at 1 year of follow-up 
• 
Estimate disease free survival (DFS) and overall survival (OS) at 1 year of follow up 
• 
Determine safety of this combination as outlined by incidence of adverse events (AEs) based on 
CTCAE v5.0 
Correlative 
Objectives: 
• 
Change in level of expression of CD38 on leukemic blasts and normal tissue over time as 
determined by CD38 measurement by flow cytometry on predefined time points 
• 
Determination of the PK of FT538 in the peripheral blood and marrow 
• 
Clinicopathological correlates of efficacy (level of CD38 expression, cytogenetics and molecular 
classification of the disease) 
• 
Clinicopathological correlates of safety (level of CD38 expression, cytogenetics and molecular 
classification of the disease) 
• 
Characterization of the kinetics of changes in CD38-expressing host immune cell populations 
including NK, Treg and MDSCs after exposure to daratumumab 
Disease 
Related 
Inclusion: 
Acute myeloid leukemia relapsed/refractory after 2 lines of therapy with CD38 expression  
• 
CD38 expression is defined by ≥20% of malignant cells with CD38 expression by flow cytometry on 
the most recent marrow biopsy (must be within 30 days of study enrollment).  
• 
Relapsed/refractory is defined as failure to achieve at least a Morphological Leukemia Free State 
(MLFS) or reverting from MLF i.e. any level of blasts detected by flow cytometry.  
• 
Lines of therapy are defined as: 
o 
One cycle of Intensive induction chemotherapy such as 7+3, 5+2, MEC, FLAG, FLAG-Ida, or 
CLAG ± small molecule inhibitor 


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o 
Four weeks of HMA-based induction ± small molecule inhibitor 
o 
Hematopoietic stem cell transplantation (HSCT), must be >90 days post 
o 
Gemtuzumab Ozogamicin 
o 
LDAC + glasdegib 
o 
Biomarker-specific targeted agents (FLT3 inhibitors, IDH1/2 inhibitors, others if available) 
o 
Other treatments maybe considered after discussion with the PI 
Key Inclusion 
Criteria: 
• Age 12 years or older at the time of consent 
• Weight ≥ 50 kg due to FT538 fixed cell dosing and FT538 product pre-dosed packaging 
• Karnofsky performance status of 70-100% for age ≥16 years, Lansky play score of 70-100 for age 
<16 years 
• Evidence of adequate organ function within 14 days prior to starting study treatment defined as: 
o Estimated Glomerular Filtration Rate (estimated creatinine clearance) ≥50 mL/minute  
o Total bilirubin ≤ 5 × upper limit normal (ULN), not applicable for patients with Gilbert’s syndrome 
• AST ≤3 × ULN and ALT ≤ 3 × ULN, not applicable if determined to be directly due to underlying 
malignancy Sexually active women of child-bearing potential and males with female partners of 
childbearing potential must agree to use must use a highly effective form of contraception as detailed 
in Section 4.2.5 
• Must agree to and sign the consent for the companion Long-Term Follow-Up study to fulfill the FDA 
required 15 years of follow-up for a genetically modified cell product   
• Patient ≥18 years provides voluntary written consent prior to the performance of any research related 
procedure. Minors (<18 years) provide voluntary written assent with the parent/guardian signing the 
treatment consent prior to the performance of any research related procedure.  
Key Exclusion 
Criteria: 
• Diagnosis of acute promyelocytic leukemia (APL)  
• Pregnant or breastfeeding, Menstruating females of child-bearing potential must have a negative 
pregnancy test within 14 days of study treatment start 
• Known allergy to any of study drugs or their components 
• Clinically significant cardiovascular disease including any of the following: myocardial infarction within 
6 months prior to first study treatment; unstable angina or congestive heart failure of New York Heart 
Association Grade 2 or higher or cardiac ejection fraction <40% 
• Any known condition that requires systemic immunosuppressive therapy (> 5mg prednisone daily or 
equivalent) during the FT538 dosing period (3 days before the 1st dose through 14 days after the last 
dose) excluding pre-medications – inhaled and topical steroids are permitted 
• Receipt of any biological therapy, chemotherapy, or radiation therapy, except for palliative purposes, 
within 2 weeks prior to Day 1 or five half-lives, whichever is shorter; or any investigational therapy 
within 28 days prior to the to the first dose of daratumumab.  
• Known active central nervous system (CNS) involvement or treated CNS disease that has not cleared. 
If prior disease- related CNS involvement, then must have completed effective treatment of their CNS 
disease  
• Non-malignant CNS disease such as epilepsy, CNS vasculitis, or neurodegenerative disease or 
receipt of medications for these conditions in the 2-year period leading up to study enrollment   
• Clinically significant untreated/uncontrolled infection 
• Live vaccine <6 weeks prior to start of lympho-conditioning 
• Known seropositive for HIV or known Hepatitis B or C infection with detectable viral load by PCR 
• Prior solid organ transplant 
• Allogeneic HSCT within previous 90 days  
• Active GVHD requiring systemic immune suppression within 14 days prior to enrollment 
• Presence of any medical or social issues that are likely to interfere with study conduct or may cause 
increased risk to the participant. 
Enrollment 
Plan: 
Enrollment for adults on this trial will not begin until all patients on the AML monotherapy Dose Cohort 1 
clear the DLT window in the Fate sponsored Protocol FT538-101: FT538 as Monotherapy and in 
Combination with mAbs in Advanced Hematologic Malignancies. 
 


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Enrollment of pediatric patients 12 years and older will not begin until a minimum of 6 adults are 
treated on this study and/or the combination arm on FT538-101 and safety data is submitted to the FDA 
for their review and permission to proceed with the enrollment of children is received. 
 
Enrollment will most likely include 17 patients or it could be as high as 25 patients if DLTs are encountered 
early. With 10-12 patients enrolled per year, accrual is expected to be completed within 1.5 to 2 years. 


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Study Schema (Amended 03/01/2023)1 
There is no Day 0 in this treatment plan. 
 
                                                            DLT Assessment Period through Day 29         
         
                                                     
                                                                                                                                                                       
                                                                                                                                                              assess         end            end  
                                              D   CY    CY         FT538             FT538            FT538            response   of DLT     of SR      Follow-up (months from Day 1) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study Day                       -6    -5    -4   -3   -2         1          3         8        10         15                 22           29         42        3 mon  6 mon  9 mon  12 mon*      
No Day 0 
 
D:  DARZALEX FASPRO (1,800 mg daratumumab and 30,000 units hyaluronidase) administered subcutaneously (subQ) once on Day 
-5  
 
FLU: fludarabine (FLU) 25 mg/m2 administered by IV infusion for 5 consecutive days, Day -6, Day -5, Day -4, Day -3, and day -2. 
 
CY: Cyclophosphamide 60 mg/kg  administered by IV infusion for 2 consecutive days, Day -4 and Day -3   
 
FT538: administered at assigned dose as an IV infusion via gravity on Day 1, Day 8, and Day 15  
 
All patients are monitored for dose limiting toxicities (DLTs) and unacceptable toxicity using early stopping rules (SRs)  
Day 29 end of dose limiting toxicity (DLT) assessment (DLTs are defined on the next page and in Section 6.3.1 of the protocol) 
Day 42 end monitoring for excessive toxicity (SR events are defined on the next page and in Section 6.3.2 of the protocol) 
 
*after the 12 month visit, follow-up transfers to the long-term follow-up (LTFU) study  
 
Up to 5 dose levels of FT538 will be tested (including, a DL -1, only used in event of DLT at DL 1): 
 
Dose Level (DL) Cohort 
FT538 cells/dose 
-1 
5 x 107  
1 (start) 
1 × 108  
2 
3 × 108  
3 
1 × 109  
4 
1.5 × 109  
Each DL Cohort is separated by a minimum of 28 days (end of the DLT period). A minimum of 14 days must pass between the enrollment 
of the 1st and the 2nd patient in 3 patient cohorts.  
 
 
1 Subjects enrolled prior to 16-Nov-2022 received Cy-Flu lymphodepletion on day -4 and day -3 only; subjects enrolled prior to 20-Mar-
2023 received 5 doses of daratumumab on day -12, -5, day +3 and day +17. See Appendix V for previous versions of schema. 
FLU 




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1 
Objectives 
1.1 Primary Objective 
The primary objective of this study is to determine the maximum tolerated dose 
(MTD) of FT538 when given in combination with daratumumab in the treatment of 
acute myeloid leukemia. 
1.2 Secondary Objectives 
• To obtain preliminary estimates of efficacy as measured by the objective 
response (CR + CRi) assessed by Day 28, the primary trial endpoint based on 
the 2017 European LeukemiaNet (ELN) response criteria (Döhner 2017) 
• Determine the overall response rate (ORR) at 1 year of follow-up 
• Determine progression free survival (PFS) and overall survival (OS) at 1 year 
of follow up 
• Determine safety of this combination as outlined by incidence of adverse events 
(AEs) measured by CTCAE v5.0 
1.3 Correlative Objectives 
Correlative/exploratory objective include: 
• Change in level of expression of CD38 on leukemic blasts and normal tissue 
over time as determined by CD38 measurement by flow cytometry on 
predefined time points 
• Determination of the PK of FT538 in the peripheral blood and marrow 
• Clinicopathological correlates of efficacy (level of CD38 expression, 
cytogenetics and molecular classification of the disease) 
• Clinicopathological correlates of safety (level of CD38 expression, cytogenetics 
and molecular classification of the disease) 
• Characterization of the kinetics of changes in CD38-expressing host immune 
cell populations including NK, Treg and MDSCs after exposure to 
daratumumab 
2 
Background and Significance 
2.1 Introduction and Disease Under Treatment  
Treatment of relapsed and refractory acute myeloid leukemia (AML) remains an 
unmet need given that most patients are diagnosed at an advanced age and have 
significant comorbidities. Strategies other than cytotoxic chemotherapy are 
desperately needed. CD38 is an ADP ribosyl cyclase membrane glycoprotein that 
is expressed in the majority of lymphocytes and on early myeloid precursors. 
(Drach 1994) Its presence has been has been variably reported on AML blasts. 
(Dos Santos 2014) We examined 51 bone marrow aspirates for presence of 


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absence of CD38 by clinical-grade multicolor flow cytometry and found 39/51 
(76%) to have some level of expression of CD38 on AML blasts.(unpublished data) 
Ligation and activation of CD38 has been linked to increased superoxide 
generation and increase in colony forming units of cell line.(Malavasi 2008) 
Inhibition of CD38 with DARA has been shown to decrease leukemia cell growth 
by inhibiting mitochondrial transfer and oxidative phosphorylation. (Mistry 2019) 
The expression of CD38 has also been shown to increase after exposure to ATRA 
through induction of differentiation through the RARa receptor. (Drach 1994, 
Buteyn 2018) Targeting AML cells using CD38 has been attempted using DARA 
in vitro. NSG cells were transplanted with T-cell depleted AML and treated with 
DARA or controls. The treated mice showed a reduction in tumor burden in the 
spleen and peripheral blood but not bone marrow aspirates. (Dos Santos 2014)  
This provides a rationale for targeted CD38 in AML. 
2.2 Natural Killer Cells 
Cancer immunotherapy is a rapidly evolving field that has transformed the 
treatment of many tumor types, including advanced hematologic malignancies. 
Key advancements in this field include the development of mAbs that block key 
inhibitory pathways on T cells, such as those that block programmed cell death 
receptor-1 (PD-1) and programmed cell death ligand-1 (PD-L1), and the 
development of adoptive transfer of immune cells as exemplified by chimeric 
antigen receptor (CAR) T-cell therapy. Both approaches have led to the 
development of novel therapeutic regimens that have increased survival in patients 
with a variety of solid and hematopoietic tumors. However, despite these important 
advances, the majority of patients will either not respond or eventually experience 
disease relapse. Further understanding of the biology that enables these cells to 
enter tumors and retain anti-tumor cytotoxic activity is important in order to 
maximize their clinical benefit for patients. 
NK cells are so named for their “natural” ability to kill cancer cells without prior 
sensitization (Kiessling 1975). NK cells target and kill cancer cells by multiple 
mechanisms (Figure 3), including direct cytotoxicity, cytokine secretion, and 
ADCC, which support their clinical investigation in oncologic indications as 
monotherapy and in combination with mAb therapy as follows: 
• Direct cytotoxicity through the targeted release of perforins and granzymes. 
Importantly, while major histocompatibility complex class I (MHC-I)-deficient 
cells evade CD8 T-cell recognition, they are preferential targets for NK cells 
and are highly susceptible to NK-cell-mediated killing (Malmberg 2017). 
• Secretion of cytokines, including interferon-gamma (IFNγ) and tumor necrosis 
factor-alpha (TNFα), promote direct tumor-cell killing (Wang R 2012). 


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• ADCC, which occurs when an antibody binds to a tumor cell and the antibody’s 
Fc region binds to the CD16 receptor on NK cells, triggering a targeted and 
engaged cytotoxic response toward the tumor cell (Waldhauer 2008; Wang W 
2015). 
In addition to direct effects on tumor cells, NK cells can interact with the adaptive 
immune system to generate and maintain adaptive immune responses against 
cancer cells as follows: 
• Killing of tumor cells by NK cells results in the release of tumor antigens for 
recognition by the adaptive immune system (Dahlberg 2015).  
• Upon activation, NK cells secrete cytokines that recruit and activate 
endogenous T cells. Importantly, activated NK cells are potent producers of 
chemokines such as CXCL10, CCL4, and CCL5, which are known recruitment 
factors for T cells. Cytokines secreted by NK cells also induce maturation of 
dendritic cells, which serve as antigen-presenting cells to mediate adaptive 
immune responses (Smyth 2002). 
Through these aforementioned mechanisms, NK cells have the intrinsic potential 
to bridge the innate and adaptive immune response and turn a tumor that is 
immunologically “cold” to one that is “hot,” characterized by an increased immune 
infiltrate that can potentially restore adaptive immune function. 
In clinical investigations, allogeneic NK-cell therapies have been well tolerated with 
documented anti-tumor activity. More than 500 patients across 30 completed 
clinical studies have received allogeneic NK cells (Veluchamy 2017). Notably, and 
unlike allogeneic T-cell therapies, allogeneic NK cells have not been associated 
with graft-vs-host disease (GvHD). Furthermore, with the exception of NK cells 
combined with a potent IL-15 agonist (Cooley 2019), allogeneic NK-cell therapies 
have not been associated with cytokine release syndrome (CRS) or neurotoxicity, 
which are common complications observed with CAR T-cell therapies. Complete 
remission rates ranging from 21% to 53% have been observed following a single 
administration of allogeneic NK cells in subjects with relapsed/refractory (r/r) AML 
(Miller 2005; Bachanova 2014; Romee 2016), and in subjects with poor prognosis 
refractory non-Hodgkin lymphoma (Bachanova 2018). Clinical responses have 
also been reported in subjects with solid tumors, including non-small cell lung 
cancer (Iliopoulou 2010; Tonn 2013), as well as in subjects with platinum-resistant 
ovarian cancer (Geller 2011), melanoma (Arai 2008), and renal cell carcinoma 
(Arai 2008). 
 
 


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2.3 FT538 
FT538 is an allogeneic natural killer (NK)-cell immunotherapy produced from a 
clonal master human-induced pluripotent stem cell (iPSC) line with the following 
engineered elements: a) deletion of the gene encoding CD38 (i.e., CD38 knockout 
[KO]; Bjordahl 2019; Cichocki 2019); b) high-affinity, non-cleavable CD16 receptor 
(hnCD16; Jing 2015; Zhu 2020); and c) interleukin (IL)-15/IL-15 receptor alpha 
fusion protein (IL-15RF; Rubinstein 2006; Stoklasek 2006). The clonal master cell 
bank (MCB) used for the production of FT538 was generated by selecting and 
expanding a single well-characterized iPSC clone in which a single 
IL15RF/hnCD16 expression cassette was inserted into the CD38 gene locus 
through non-viral-mediated targeted transgene integration. The use of a clonal 
MCB as the starting material for routine current Good Manufacturing Practices 
(cGMP) production of FT538 is intended to directly address many of the limitations 
associated with patient- and donor-specific cell therapies. Notably, many doses of 
FT538 drug product can be uniformly produced in a single manufacturing 
campaign. These doses of drug product are homogeneous and are: (i) tested to 
assure compliance with a pre-defined quality specification, (ii) cryopreserved in an 
infusion medium, and (iii) stored to maintain a sustainable inventory. As such, 
FT538 in the clinical setting has off-the-shelf availability for use in multi-dose 
regimens, which may prove critical for driving long-term durable responses in 
patients with progressing disease. 
The engineered features of FT538 are designed to result in increased activity 
against target tumor cells as monotherapy and when combined with monoclonal 
antibodies (mAbs) that can mediate antibody-dependent cellular cytotoxicity 
(ADCC). Important functional attributes of FT538 include the following: 
• FT538 is expected to have superior effector function compared to patients’ 
endogenous NK cells, which are typically diminished in number and function 
due to prior treatment regimens (e.g., chemotherapy) and tumor suppressive 
mechanisms. FT538 mediates “innate cytotoxicity” that is potent and specific 
to transformed cells. 
• The CD38 gene KO in FT538 is intended to prevent anti-CD38 antibody-
mediated NK-cell fratricide and consequently enhance ADCC when FT538 is 
administered with concurrent anti-CD38 mAb therapy (Bjordahl 2019). In 
addition, NK cells with CD38 KO have been shown to be more resistant to 
oxidative stress and exhibit enhanced effector function (Cichocki 2019). 
• FT538 expresses an hnCD16 Fc receptor. The high-affinity CD16 variant 
arising from a naturally occurring 158V polymorphism has demonstrated 
enhanced ADCC when combined with therapeutic mAbs in nonclinical studies. 
In clinical studies evaluating patients whose endogenous NK cells express the 


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high-affinity CD16 Fc receptor variant, higher objective response rates and 
increased progression-free survival (PFS) were observed with treatment with 
rituximab, cetuximab, and trastuzumab (Cartron 2002; Musolino 2008; Bibeau 
2009). In addition, hnCD16 contains the genetic alteration (S179P) that 
prevents cleavage of CD16 by the metalloproteinase ADAM17 (Lajoie 2014; 
Jing 2015), a mechanism in the regulation and attenuation of NK-cell activity 
by the tumor microenvironment (Romee 2013). 
 
FT538 expresses IL-15RF, designed to provide an endogenous activation and 
proliferation signal, reducing the dependence on exogenous cytokine 
administration such as IL-2 and IL-15, both of which have been associated with 
significant toxicities that may limit clinical usage when incorporated into clinical 
studies of peripheral blood NK cells (Cooley 2019). 
 
These features justify investigation of FT538 in a broad array of oncology 
indications including, but not limited to, the following:  
• 
As monotherapy, e.g., acute myelogenous leukemia (AML), where FT538 may 
provide greater clinical benefit than current allogeneic NK-cell-based 
therapies. 
• 
In combination with approved and investigational tumor-targeting, ADCC-
capable mAbs, including daratumumab, which target CD38, and are approved 
for the treatment of patients with multiple myeloma (MM). 
2.4 The Role of Daratumumab and Use of subQ DARZALEX FASPRO 
Daratumumab (DARA) is a monoclonal IgG1κ antibody against CD38, a 
transmembrane glycoprotein with both receptor and enzymatic functions 
expressed on hematopoietic cells. It was approved by the FDA in 2015 for the 
treatment of multiple myeloma. DARA binds the CD38 antigen and induces cellular 
lysis through complement activity, antibody-dependent toxicity, antibody-
dependent cellular phagocytosis, and direct apoptosis. 
A formulation of daratumumab for subcutaneous administration was developed to 
shorten the time required to administer daratumumab and to lessen the incidence 
and severity of infusion related reactions (IRRs) observed with intravenous (IV) 
daratumumab. A recombinant human hyaluronidase PH20 (rHuPH20) was used 
to decrease the injection volume required, facilitating the subcutaneous 
administration of daratumumab. FDA approval DARZALEX FASPRO was received 
in April 2020 for the treatment of adults with multiple myeloma as a monotherapy 
and in combination with select standard of care drugs. (DARZALEX FASPRO 
Prescribing Information) 


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In a pooled safety population of 490 patients who received DARZALEX FASPRO 
as monotherapy or in combination, 11% of patients experienced a systemic 
administration-related reaction (Grade 2: 3.9%, Grade 3: 1.4%). Systemic 
administration-related reactions occurred in 10% of patients with the first injection, 
0.2% with the second injection, and cumulatively 0.8% with subsequent injections. 
The median time to onset was 3.7 hours (range: 9 minutes to 3.5 days). Of the 84 
systemic administration-related reactions that occurred in 52 patients, 73 (87%) 
occurred on the day of DARZALEX FASPRO administration. Delayed systemic 
administration-related reactions have occurred in less than 1% of the patients. 
(DARZALEX FASPRO Prescribing Information) 
2.5 Lymphodepletion with Cyclophosphamide and Fludarabine  
The importance of lymphodepleting chemotherapy has been well demonstrated in 
mouse experiments and was first proposed by the National Cancer Institute (NCI) 
in the context of melanoma specific CTL by Rosenberg and colleagues. (Dudley 
2002) Lymphodepleting conditioning prior to adoptive transfer of lymphocytes is 
thought to promote persistence of adoptively transferred lymphocytes by creating 
"immunologic space” and providing a pool of homeostatic cytokines such as IL-15. 
The use of Cy/Flu-mediated lymphodepletion at the proposed doses and schedule 
is consistent with our previous human experience. (Miller 2005, Bachanova 2014) 
We and others (Buteyn 2018, Dos Santos 2014, Drach 1994) have demonstrated 
that CD38 is present on hematopoietic cells. The expression on NK cells is in part 
the rationale for the CD38 knockout in the therapeutic product FT538. However, 
the proposed therapy plan may have an additional therapeutic advantage to target 
CD38 expressing regulatory T cells (Treg) and myeloid-derived suppression cells, 
depletion of which could enhance the anti-tumor activity of immunomodulatory 
therapies. Thus, the combination of FT538 and Daratumumab is expected to have 
three therapeutic mechanisms of action in this protocol: 1) to target host immune 
suppressor cells and enhance NK cell adoptive transfer by enhancing 
lymphodepletion, 2) direct targeting of CD38 on AML cells and 3) providing the 
killing mechanism of natural cytotoxicity by which NK cells recognize AML targets 
independent of antibody dependent cellular cytotoxicity (e.g. through down 
regulation of MHC class I and upregulates of stress ligands on AML; both 
increasing recognition and AML killing by NK cells). 
 
For the protocol amendment version dated 24 November 2022: Five patients have 
enrolled per Stage 1 Step 1 process, 4 have received FT538 with no related G3/4 
AEs or DLTs, with most current patient on dose level 4 . However, we have not 
seen any signal of efficacy. Correlatives drawn to track the expansion of the cells 
have shown poor expansion. In order to determine factors that may contribute to 
increased FT538 pharmacokinetics, we have increased the initial lymphodepletion 


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to reflect a more established regimen that has been previously described as 
effective with acceptable safety parameters [Miller et al. Blood. 2005]. 
 
Amendment March 2023: In the original treatment plan we had hypothesized that 
multiple doses of daratumumab might allow lower doses of cyclophosphamide and 
fludarabine (as used in enrollment to date) to prolong the pharmacokinetics of the 
FT538 NK cell product. However, new information on subjects treated to date 
shows that FT538 persistence in vivo was not achieved at 14 days even at the 
highest cell doses, the biomarker goal of the treatment strategy. This was 
surprising because in our prior work, 14-day persistence was achieved in some 
subjects in various studies using high-dose cyclophosphamide and 5 days of 
fludarabine (HiCyFlu). In the November 2022 revision, we increased 
to HiCyFlu doses previously tested. With this plan, we will decrease to 1 dose of 
daratumumab as multiple doses are no longer needed to increase persistence. 
Given the long half-life of daratumumab (approximately 3 weeks), 1 dose is 
sufficient to mediate ADCC to CD38+ AML targets for the multi-dose FT538 
infusion plan while reducing the risk that study participants might develop toxicity 
requiring management with corticosteroids, which could also compromise FT538 
persistence. 
2.6 Study Rationale 
FT538 is an allogeneic natural killer (NK)-cell immunotherapy produced from a 
clonal master human-induced pluripotent stem cell (iPSC) line with the following 
engineered elements: a) deletion of the gene encoding CD38 (i.e., CD38 
knockout); b) high-affinity, non-cleavable CD16 receptor (hnCD16); and c) 
interleukin (IL)-15/IL-15 receptor alpha fusion protein (IL-15RF). 
 
The engineered features of FT538 are designed to result in increased activity 
against target tumor cells as monotherapy and when combined with monoclonal 
antibodies (mAbs) that can mediate antibody-dependent cellular cytotoxicity 
(ADCC). These features justify investigation of FT538 in advanced acute 
myelogenous leukemia (AML): 
• As monotherapy where FT538 may provide greater clinical benefit than current 
allogeneic NK-cell-based therapies as currently being tested in Fate 
Therapeutic clinical study FT538-101. 
• As proposed in this study use in combination with the tumor-targeting, ADCC-
capable mAb, daratumumab, which targets CD38. 
2.7 Rationale to Include Pediatric Patients 12 Years Old or Older 
Treatment of acute myeloid leukemia (AML) in children has improved remarkably 
during the past decades; however, pediatric patients with relapsed and refractory 
AML still have poor outcomes (Kaspers 2014, Zwaan 2015). In fact, the probability 
of long -term survival in these patients is dismal at around 35%. These outcomes 


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rely on disease-dependent characteristics which include cytogenetics, timing or 
relapse, and response to chemotherapy (Pui 2011). Moreover, intensive 
chemotherapy and allogeneic hematopoietic cell transplantation (HCT) are 
required for a cure; this can lead to significant morbidity and mortality. Considering 
poor outcome and high toxicity of current salvage therapies, new treatments are 
needed.    
 
Daratumumab has been safely and effectively administered to children to treat 
autoimmune hemolytic anemia after HCT (Schuetz 2018). Based on preclinical 
efficacy of daratumumab in acute leukemia (Bride 2018, Vogiatzi 2019) as well as 
case report of clinical efficacy of this agent in child with relapsed leukemia (Ganzel 
2018), several clinical trials are now evaluating the safety and efficacy of 
daratumumab in children with relapsed or refractory leukemia.  
 
Given the dire prognosis of relapsed or refractory AML, and to ensure justice in 
this research protocol, we have included children ≥12 years of age. We are 
including children under 45 CFR 46.405 as this research involves greater than 
minimal risk but presents the prospect of direct benefit to the individual subjects. 
We have chosen to limit the age of enrolment to children ≥12 years such that 
assent can be obtained along with the consent of their parents/guardians.  
3 
Study Design 
This Phase I open-label dose escalation study is conducted in two stages with a primary 
endpoint to identify the maximum tolerated dose (MTD) of FT538 when administered with 
daratumumab in patients 12 years and older with advanced acute myeloid leukemia 
(AML) and related myeloid diseases.  
FT538 is an off-the-shelf product comprised of allogeneic natural killer (NK)-cell 
immunotherapy lacking CD38 and expressing hnCD16 and IL-15RF. Daratumumab is a 
targeted therapy (IgG1k human monoclonal antibody) that targets CD38. 
FT538 is administered once a week for 3 consecutive weeks (Day 1, Day 8, and Day 15). 
There is no Day 0 in this treatment plan. Up to 5 dose levels will be tested. Fixed dose 
subcutaneous daratumumab is given on Day -5 prior to the FT538 cells as 
lymphodepletion. A short course of outpatient lymphodepleting chemotherapy is given 
from Day -6 through Day -3 to promote adoptive transfer. 
FT538 dose level cohorts are defined as:  
Table 1: Dose Level and Schedule 
Dose Level (DL) 
Treatment Plan for FT538 
-1 
5 x 107 cells on Day 1, Day 8 and Day 15 
1 (start) 
1 × 108 cells on Day 1, Day 8 and Day 15 


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Dose Level (DL) 
Treatment Plan for FT538 
2 
3 × 108 cells on Day 1, Day 8 and Day 15 
3 
1 × 109 cells on Day 1, Day 8 and Day 15 
4 
1.5 × 109 cells on Day 1, Day 8 and Day 15 
The trial is conducted with no intra-patient escalation.  
Enrollment on this trial will not begin until all patients on the AML monotherapy Dose 
Cohort 1 clear the DLT window in the Fate sponsored Protocol FT538-101: FT538 as 
Monotherapy and in Combination with mAbs in Advanced Hematologic Malignancies. 
UMN is a participating site in this industry sponsored trial. 
Enrollment of pediatric patients (12 years and older) will not begin until a minimum 
of 6 adults are treated on this study and/or the combination arm on FT538-101 and safety 
data is submitted to the FDA for their review and permission to proceed with the 
enrollment of children is received. 
This study is performed in two stages, with Stage 1 having two potential steps. A minimum 
of 28 days separates each patient cohort. A minimum of 14 days must pass between the 
enrollment of the 1st and the 2nd patient in 3 patient cohorts. All patients are assessed 
for Dose Limiting Toxicity (DLT) as defined in the Schema and in Section 6.3.1. 
 
STAGE 1 STEP 1 Fast-track design (1 patient per dose cohort) 
Start at Dose Level 1 (DL1), enroll 1 patient per dose cohort separated by 28 days 
(DLT period) until the:  
• 1st pre-defined adverse event defined as any Grade 3 non-hematologic AE within 
72 hours of a FT538 infusion  
• and the patient completes the 28 day DLT period with no DLT- Activate Stage 1 
Step 2 
OR  
• 1st DLT event within 28 days after the 1st dose of FT538 as defined in the Schema 
and in Section 6.3.1 - Activate Stage 2 (Stage 1 Step 2 is not used)  
OR 
• 10 patients are treated at the Dose Level 4 (This completes enrollment - Stage 1 
Step 2 and Stage 2 are not used) 
• If the first patient at dose level 4 in stage 1 step 1 completes DLT period with no 
pre-defined adverse events or DLT, successive subjects may enroll without 
staggering. 
 
STAGE 1 STEP 2 Expand current Dose Level and subsequent DLs to 3 patients 
The cohort size increases from 1 to 3 patients with 2 additional patients added to the 
current cohort. A minimum of 14 days must pass between the enrollment of the 1st 


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and the 2nd patient in 3 patient cohorts and a minimum of 28 days between dose 
cohorts. Continue dose escalation until: 
• 1st DLT event as defined in the Schema and Section 6.3.1 - Activate Stage 2 
OR  
• 10 patients are treated at the Dose Level 4 (This completes enrollment and Stage 2 
is not used.) 
• For Dose Level 4 in stage 1, step 2, second and third patients may enroll 
immediately but must complete their DLT period prior to enrolling the rest. If no 
DLT events within monitoring period, successive subjects may enroll without 
staggering.  
 
STAGE 2 Continual Reassessment Method (CRM) at the 1st DLT 
The study design changes to the CRM. Enrollment occurs in cohorts of three. A minimum 
of 14 days must pass between the enrollment of the 1st and the 2nd patient in 3 patient 
cohorts. Each new cohort of three patients is sequentially assigned to the most 
appropriate dose by the study statistician based on the updated toxicity probabilities once 
the 3rd patient in a cohort reaches Day 29 (end of DLT period). The MTD is identified by 
the minimum of the following criteria: (1) the total Stage 2 maximum sample size of 25 is 
exhausted or (2) 10 consecutive patients are enrolled at the same FT538 dose. 
 
The primary analysis for Phase I is intent-to-treat in that all patients receiving the 1st 
infusion of FT538 are evaluable for toxicity and efficacy. Patients who discontinue therapy 
prior to the first FT538 will be replaced.  
 
All patients are monitored for dose limiting toxicities (DLTs) and unacceptable toxicity 
using early stopping rules.  
 
The definition of dose limiting toxicity (DLT) is found in Section 6.3.1.  
 
The definition of excessive toxicity is found in Section 6.3.2. 
 
Follow-up: Direct study participation ends at 1 year after the 1st dose of FT538.  
 
Long-Term Follow-Up for any patient who received at least one dose of FT538: After 
1 year, follow-up transfers to a separate long-term follow-up (LTFU) study to continue the 
FDA’s recommended 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 persons 12 of age 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 that of other 
advanced AML studies at this institution. Refer to Section 4.2.1 of FDA mandated delay 
in the enrollment of minor patients. 
4.1 Disease Specific Inclusion Criteria 
Acute myeloid leukemia relapsed/refractory after 2 lines of therapy; with CD38 
expression 
4.1.1 CD38 expression is defined by ≥20% of malignant cells with CD38 
expression by flow cytometry on the most recent marrow biopsy (within 30 
days of enrollment – archived or fresh).  
4.1.2 Relapsed/refractory is defined as failure to achieve at least a Morphological 
Leukemia Free State (MLFS) or reverting from MLFS.  
4.1.3 Lines of therapy are defined as (must have had 2 prior therapies): 
• One cycle of an Intensive induction chemotherapy such as 7+3, 5+2, 
MEC, FLAG, FLAG-Ida, or CLAG ± small molecule inhibitor 
• Four weeks of HMA-based induction ± small molecule inhibitor 
• Hematopoietic stem cell transplantation (HSCT), must be >90 days 
post 
• Gemtuzumab Ozogamicin 
• LDAC + glasdegib 
• Biomarker-specific targeted agents (FLT3 inhibitors, IDH1/2 inhibitors, 
others if available) 
• Other treatments could be considered after discussion with the PI 
4.2 Inclusion Criteria 
4.2.1 Age 12 years or older at the time of consent - Please note, enrollment of 
minors will be begin until permission to proceed is received from the FDA. 
At that time, the protocol will be updated to open enrollment to minors. 
4.2.2 Weight ≥ 50 kg due to FT538 fixed cell dosing and FT538 product pre-dose 
packaging 
4.2.3 Karnofsky performance status of 70-100% for 16 years and older or Lansky 
Play Score of 70-100 for ≥12 and < 16 years of age (refer to Appendix I) 
4.2.4 Evidence of adequate organ function within 14 days prior to starting study 
treatment defined as: 
o 
Estimated Glomerular Filtration Rate (estimated creatinine clearance) 
≥50 mL/min/1.73m^2 
o Total bilirubin ≤ 5 × upper limit normal (ULN), not applicable for patients with 
Gilbert’s syndrome 
 


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o AST ≤3 × ULN and ALT ≤ 3 × ULN, not applicable if determined to be directly 
due to underlying malignancy 
4.2.5 Contraceptive use by men or women 
o 
Female subjects: Women of childbearing potential (WOCBP) must use a 
highly effective form of contraception from the screening visit until at least 
12 months after the final dose of cyclophosphamide (CY), at least 4 months 
after the final dose of FT538, and at least 4 months after the dose of 
daratumumab, whichever is latest. 
o 
Male subjects: Males with a female partner of childbearing potential or a 
pregnant female partner must be sterile (biologically or surgically) or use a 
highly effective method of contraception from the screening visit until at 
least 14 months after the final dose of CY and at least 6 months after the 
final dose of FT538, and at least 5 months after the dose of daratumumab, 
whichever is latest. 
4.2.6 Must agree to and sign the consent for the companion Long-Term Follow-
Up study to fulfill the FDA recommended 15 years of follow-up for a 
genetically modified cell product.  
4.2.7 Patient ≥18 years provides voluntary written consent prior to the 
performance of any research related procedure. Minors (<18 years) 
provide voluntary written assent with the parent/guardian signing the 
treatment consent prior to the performance of any research related 
procedure. 
4.3 Exclusion Criteria 
4.3.1 Diagnosis of acute promyelocytic leukemia (APL)  
4.3.2 Pregnant or breastfeeding, Menstruating females of child-bearing potential 
must have a negative pregnancy test within 14 days prior to study 
treatment start 
4.3.3 Known allergy to any of study drugs or their components 
4.3.4 Clinically significant cardiovascular disease including any of the following: 
myocardial infarction within 6 months prior to first study treatment; unstable 
angina or congestive heart failure of New York Heart Association Grade 2 
or higher (Appendix II) or cardiac ejection fraction <40%  
4.3.5 Any known condition that requires systemic immunosuppressive therapy 
(> 5mg prednisone daily or equivalent) during the FT538 dosing period (3 
days before the 1st dose through 14 days after the last dose) excluding 
pre-medications – inhaled and topical steroids are permitted 
4.3.6 Receipt of any biological therapy, chemotherapy, or radiation therapy, 
except for palliative purposes, within 2 weeks prior to Day 1 or five half-
lives, whichever is shorter; or any investigational therapy within 28 days 
prior to the to the first dose of daratumumab.  


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4.3.7 Known active central nervous system (CNS) involvement or treated CNS 
disease that has not cleared. If prior disease related CNS involvement 
must have completed effective treatment of their CNS disease at least 2 
months prior to Day 1 with no clinical evidence of disease  
4.3.8 Non-malignant CNS disease such as epilepsy, CNS vasculitis, or 
neurodegenerative disease or receipt of medications for these conditions 
in the 2-year period leading up to study enrollment   
4.3.9 Clinically significant untreated/uncontrolled infection 
4.3.10 Live vaccine <6 weeks prior to start of lympho-conditioning 
4.3.11 Known seropositive for HIV or known active Hepatitis B or C infection with 
detectable viral load by PCR 
4.3.12 Prior solid organ transplant 
4.3.13 Allogeneic HSCT within previous 90 days  
4.3.14 Active graft-versus-host-disease (GvHD) requiring systemic immune-
suppression within 14 days prior to enrollment 
4.3.15 Presence of any medical or social issues that are likely to interfere with 
study conduct or may cause increased risk to the participant. 
5 
Patient Screening and Enrollment 
5.1 Registration with the Masonic Cancer Center Clinical Trials Office 
Any patient who is consented is to be entered 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.  
5.2 Patient Enrollment and Dose Cohort Placement 
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. The patient is placed in the currently enrolling dose cohort. 
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 FT538, 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 


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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 at least 1 dose of FT538, they are considered on treatment 
and must continue follow-up per Section 8. 
 
6 
Treatment Plan 
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.). In this 
study, hydroxyurea may be used at any time to control peripheral blood blasts. 
 
Because they may inhibit NK cell function, additional systemic corticosteroids should 
be avoided unless absolutely required. Standard pre-medications for study drugs 
(including corticosteroids as daratumumab pre-meds) are permitted.   
 
There is some flexibility in the timing of the treatment as long as the ordering of the 
treatment is maintained and a minimum of 48 hours separates the last dose of 
fludarabine and the 1st FT538 infusion. The below Table 1 represents the treatment 
plan when Day 1 is a Monday and treatment is given as planned. 
 
Table 1. Treatment Plan Example with Day 1 = Monday 
Study Day 
Day of Week 
Agent 
Protocol Section 
Day – 6 
Tuesday 
FLU 
Section 6.2 
Day -5 
Wednesday 
Daratumumab, FLU 
Section 6.1, Section 6.2 
Day -4, Day -3 
Thursday, Friday 
CY/FLU 
Section 6.2 
Day -2 
Saturday 
FLU 
Section 6.2 
Day 1 
Monday 
FT538 
Section 6.3 
Day 8 
Monday 
FT538 
Section 6.3 
Day 15 
Monday 
FT538 
Section 6.3 
 
There is no Day 0 in this treatment plan. 
6.1 Daratumumab Administration Guidelines 
Daratumumab subQ 1800 mg co-formulated with 30,000 units of hyaluronidase 
(rHuPH20) into the subcutaneous tissue of the abdomen approximately 3 inches 
[7.5 cm] to the right or left of the navel over approximately 3-5 minutes on Day -5 
prior to the 1st FT538 infusion. 
 
• Never inject DARZALEX FASPRO into areas where the skin is red, bruised, 
tender, hard, or areas where there are scars. 


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• Pause or slow down delivery rate if the patient experiences pain. In the event 
pain is not alleviated by pausing or slowing down delivery rate, a second 
injection site may be chosen on the opposite side of the abdomen to deliver the 
remainder of the dose. 
• During treatment with DARZALEX FASPRO, do not administer other 
medications for subcutaneous use at the same site as DARZALEX FASPRO. 
 
Pre- and Post-Medications: 
Administer the following pre-medications 1-3 hours before daratumumab: 
• Acetaminophen 650 to 1,000 mg orally 
• Diphenhydramine 25 to 50 mg (or equivalent) orally or intravenously 
• Methylprednisolone 60 mg (or equivalent) orally or intravenously. Dose Day -5 
and Day -4. 
 
Refer to Section 2.4 for injection related reaction presented in the current 
Investigator Brochure. With the subcutaneous route, in a pooled safety population 
of 490 patients who received DARZALEX FASPRO as monotherapy or in 
combination, 11% of patients experienced a systemic administration-related 
reaction (Grade 2: 3.9%, Grade 3: 1.4%). Systemic administration-related 
reactions occurred in 10% of patients with the first injection, 0.2% with the second 
injection, and cumulatively 0.8% with subsequent injections.   
 
For patients with a history of chronic obstructive pulmonary disease, consider 
prescribing short and long-acting bronchodilators and inhaled corticosteroids. F 
 
Prophylaxis for Herpes Zoster Reactivation: 
Initiate antiviral prophylaxis to prevent herpes zoster reactivation within 1 week 
after starting DARZALEX FASPRO and continue for 3 months following the end of 
treatment. 
 
Monitoring: 
Monitor patients for systemic administration-related reactions and localized 
injection site reaction.  
 
A recommended post-injection observation is 3.5 hours with vital signs 
documented prior to the injection and post injection per institutional standards. 
 
For anaphylactic reaction or life-threatening (Grade 4) administration-related 
reactions, immediately and permanently discontinue DARZALEX FASPRO. 
Consider administering corticosteroids and other medications after the 


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administration of DARZALEX FASPRO depending on dosing regimen and medical 
history to minimize the risk of delayed (defined as occurring the day after 
administration) systemic administration-related reactions. 
 
Subcutaneous administration of daratumumab may be associated with a local 
injection site reactions, such as induration and erythema. The reactions usually 
resolved within 60 minutes. Local injection site reactions should be managed per 
institutional standards. 
 
DARZALEX FASPRO dose reductions are not recommended. Skipped or delayed 
dosing is permitted. 
6.2 Cyclophosphamide/Fludarabine Lymphodepletion Guidelines 
A lymphodepleting regimen of fludarabine and cyclophosphamide is given in the 
outpatient clinic on 5 consecutive days (Day -6, Day -5, Day -4, Day -3 and Day -
2). 
 
The administration of the preparative regimen will follow the institutional dosing 
guidelines. Dose and/or schedule adjustments consistent with the standard of care 
may be made on an individual patient basis as needed for safety.  
 
Fludarabine 25 mg/m2 is administered as a 1 hour intravenous (IV) infusion per 
institutional guidelines once a day on 5 consecutive days (Day -6, Day -5, Day -4, 
Day -3 and Day -2). 
 
Cyclophosphamide 60 mg/kg is administered as a 2 hour intravenous infusion per 
institutional guidelines once a day on Day -4 and Day -3. 
  
Cyclophosphamide dosing is calculated based on ABW (Actual Body Weight) 
unless ABW is >150% of the IBW (Ideal Body Weight). 
Adjusted body weight = IBW + 0.5(ABW-IBW). 
 
Cyclophosphamide associated hydration will be given according to recommended 
institutional standards. 
6.3 FT538 Administration 
FT583 is given in the same manner for all patients treated on this study. Refer to 
Section 3 for the study design/enrollment plan. 
 


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FT538 will be provided by Fate Therapeutics as cryopreserved dose specific bags 
and stored at the Molecular Cellular Therapy (MCT) Laboratory until needed. 
FT538 is thawed on the unit prior to administration. 
 
FT538 is administered as an IV infusion via gravity using an IV administration set 
with an in-line filter at the patient’s assigned dose levels on Day 1, Day 8, and 
Day 15. Refer to Table 2 below. 
 
Table 2: FT538 cell product dose levels (bag requirements) 
Dose Level 
FT538 cells 
-1 
5 × 107 FT538 cells/dose (1 bag at 5 × 107 cells/bag) 
1 (start) 
1 × 108 FT538 cells/dose (1 bag at 1 × 108 FT538 cells/bag) 
2 
3 × 108 FT538 cells/dose (3 bags at 1 × 108 FT538 cells/bag) 
3 
1 × 109 FT538 cells/dose (2 bags at 5.0 × 108 FT538 cells/bag) 
4 
1.5 × 109 FT538 cells/dose (3 bags at 5.0 × 108 FT538 cells/bag) 
Dosing is based on hnCD16 expression, where 90%±10% of FT538 cells express hnCD16. 
 
FT538 Thawing Overview: FT538 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. FT538 is stable for up to 60 minutes post-thaw. Administration of the 
cell product must begin within 60 minutes of thawing.  
FT538 Infusion guidelines: FT538 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.  
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 FT538 and 4-6 hours later, patients 
should receive acetaminophen 650 mg orally (PO) and diphenhydramine 25 PO. 
Corticosteroids should not be used as pre-medication for FT538. 
Vital Signs: Vital signs (temperature, systolic and diastolic blood pressure, heart 
rate, and respiration rate) are performed in association with the FT538 infusion at 
the following time points: within 15 minutes of the infusion start, at 10 (±5) minutes 


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during infusion, and every 15 (±5) minutes for 1 hour after the end of the last 
administered bag of FT538. 
 
Collection of research sample 30 (±5) minutes after the last bag of FT538 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 FT538 
infusion must be documented (and if applicable reported as a dose limiting toxicity 
and/or an SAE). 
 
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 receives supportive care 
per Section 7.1 guidelines. The patient will receive no further FT538.  
 
All patients are monitored for adverse events, dose limiting toxicity, stopping rule 
events, and death per Section 10. 
 
Refer to Section 7 for management of FT538 related toxicity. 
6.3.1 Dose Limiting Toxicity 
Dose limiting toxicity (DLT) is defined as any AE (based on CTCAE v5) that is at 
least possibly related to FT538 and not related to disease progression that occurs 
after the first FT538 infusion through the end of the DLT assessment period on 
Day 29 as defined below: 
 
 


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Table 3: Definition of Dose Limiting Toxicity  
Dose Limiting Toxicity (DLT)  
Exceptions 
• Any Grade 4 non-hematologic AE  
• Fever associated with CRS that occurs in 
the context of Grade <3 CRS 
• Grade 3 pulmonary or cardiac AE of 
any duration 
• Grade 3 immune cell associated 
neurotoxicity syndrome (ICANS) of any 
duration 
• Any other Grade 3 non-hematologic AE 
of >72 hours duration* 
• Grade 3 renal or hepatic AE lasting < 7 
days 
• Grade 3 fatigue lasting ≤ 3 days 
• Grade 3 laboratory abnormality, unless 
otherwise specified that is asymptomatic 
and not clinically significant 
• Grade ≥2 acute GvHD requiring 
systemic steroid administration 
 
* Note: Febrile neutropenia is not a hematologic AE or laboratory abnormality 
6.3.2 Monitoring for Excessive Toxicity  
All patients receiving the FT538 cell product will be monitored for unacceptable 
toxicity using early study stopping rules (SR). The following events are considered 
excessive toxicity per Section 12.4. 
• Excessive treatment emergent adverse events that meet DLT criteria within the 
DLT period - The trial will be stopped if the posterior probability that the lowest 
dose is unacceptably toxic (> 25% of patients) is greater than 80%; 
• Grade 4 or greater FT538 infusion related reaction; 
• Aplasia at Day 42 (ANC <500) after at least 1 week of growth factor (i.e. G-CSF)  
with an aplastic bone marrow in the absence of leukemia (<5% cellularity); 
• Any death within 28 days after the last dose of FT538 and not attributable to 
disease progression.  
6.4 Permitted and Prohibited Concomitant Medications/Therapies 
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.). 
Growth factor should be avoided until 3 days after the last dose of FT538 unless 
medically indicated. If at Day 29, bone marrow recovery is delayed, growth factor 
(i.e. G-CSF) should be initiated. Aplasia at Day 42 after at least 1 week of GF is 
considered excessive toxicity as detailed in Section 6.3.2. 
 
At the treating investigator’s discretion, hydroxyurea may be used at any time to 
control peripheral blood blasts and/or white blood count. Although classified as a 
chemotherapy, in this situation it is considered suppressive only and part of 
supportive care as it has no impact on actual disease blasts.  Consequently, the 
use of hydroxyurea would not affect a patient’s evaluability for response and 
toxicity. 


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Systemic corticosteroids should be avoided during the treatment cycle, unless 
absolutely required, because they may inhibit NK-cell function. Because of their 
deleterious effect on NK-cell-based therapy, corticosteroids as pre-medication 
should be avoided unless considered necessary by the investigator and should not 
be administered within 24 hours before or after FT538 administration. Guidelines 
regarding the use of corticosteroids for daratumumab for injection-related reaction 
prophylaxis are described in Section 6.1.  
 
Long-acting corticosteroids, such as dexamethasone, should not be used as pre-
medication for FT538 infusion-related reaction prophylaxis.  
 
Prohibited therapies include any antineoplastic agent for therapeutic intent other 
than protocol-directed study treatment while on study treatment.  
6.5 Duration of Treatment 
Treatment consists of a single course of treatment over approximately 5 weeks 
unless unacceptable toxicity, rapidly progressing disease, patient refusal, or the 
treating investigators feels treatment is not in the best interest of the patient. 
 
An End of Treatment (EOT) assessment occurs at Day 29 to confirm no ongoing 
side effects/toxicity related to study treatment. If ongoing toxicity, it should be 
managed as medically appropriate and documented, it if meets the criteria for 
documenting as an AE be followed until resolution or stabilization.  
Patients are monitored for unacceptable toxicity using early study stopping rules 
(SR) through Day 42. 
 
Any patient receiving at least one dose of FT538 is followed per Section 8.1 and 
on the Long-Term Follow-Up protocol per Section 6.7. 
6.6 Follow-Up for Disease Response and Survival (Duration of Study 
Participation) 
Patients are followed for disease response until disease progression/relapse and 
then survival until the end of the 12 month follow-up period (from the 1st dose of 
FT538). 
 
Follow-up assessments may be in person, by medical record review, or local 
medical doctor if patient is no longer seen at the treating institution. In person 
follow-up visits solely for this research study are not required and may be linked 
with a standard of care visit. Refer to Section 8 for allowable time related windows 
around each follow-up time points. 


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Follow-up may end early if any of the following apply: 
• consent is withdrawn  
• patient did not receive FT538 – if a patient is not evaluable, follow only until the 
resolution or stabilization of treatment related toxicity 
• new anti-cancer treatment is started (follow for survival only) 
• patient is discharged to hospice (terminal) care    
 
If a person ends follow-up before the 12 months study period (i.e. withdraws 
consent, lost to follow-up), public records will be searched for survival information 
for the survival endpoint. 
 
Any patient receiving at least 1 dose of FT538 must be followed for up to 15 years 
per a separate long-term follow-up protocol for late effects and survival regardless 
of status on the treatment protocol per Section 6.7.  
6.7 Continuation of Follow-Up via a Separate Long-Term Follow-Up Protocol 
FT538 is an engineered cellular immunotherapy product and the long-term safety 
risk is not known and may include conditions with delayed onset relative to FT538 
administration. Specific conditions potentially related to engineered cellular 
immunotherapy products such as FT538, 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. 
 
This LTFU reporting requirement is fulfilled through a separate study. Consent to 
the LTFU study is obtained at the time of consent for the treatment study and a 
condition for eligibility to receive treatment. If a patient does not receive FT538, 
follow-up on the LTFU study is not relevant. Refer to the LTFU protocol for 
withdrawal procedures.  
 
7 
Recommended Management Guidelines for Specific Adverse 
Events Associated with FT538 
Refer to Section 6.1 for management of daratumumab injection related reactions 
and Section 9.2.7 for potential risks. 
 
Refer to Appendix III for potential toxicities for the cyclophosphamide and 
fludarabine. 
 
 


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No FT538 clinical data are available. For this reason: 
1) Enrollment of adult patients on this trial will not begin until all patients on the AML 
monotherapy Dose Cohort 1 clear the DLT window in the Fate sponsored 
Protocol FT538-101: FT538 as Monotherapy and in Combination with mAbs in 
Advanced Hematologic Malignancies. UMN is a participating site in the industry 
sponsored trial. 
2) Enrollment of pediatric patients (12 years through 17 years) will not begin until a 
minimum of 6 adults are treated on this study and/or the combination arm on 
FT538-101 and safety data is submitted to the FDA for their review and 
permission to proceed with the enrollment of children is received. 
The long-term safety risk is not known and may include conditions with delayed 
onset relative to FT538 administration. 
 
Suggested guidelines for the management of specific AEs are outlined below. 
 
 
Dose and schedule modifications of FT538 for AEs are as follows: 
• If a Grade 3 or Grade 4 DLT is observed, then the subsequent FT538 infusions 
could be omitted. 
• If a Grade 3 non-hematologic AE that is not a DLT is observed and recovers to 
baseline by the subsequent scheduled FT538 infusion, then FT538 could be dose-
reduced to at least one lower dose level. 
o Dose reduction will not be required for Grade 3 laboratory abnormalities that are 
not clinically significant 
• If a Grade 3 non-hematologic AE that is not a DLT is observed and ongoing at the 
time of the subsequent scheduled FT538 infusion, FT538 infusion will be delayed 
until resolution of the AE to baseline, at which time FT538 could be dose-reduced 
to at least one lower dose level. 
o Dose reduction will not be required for Grade 3 laboratory abnormalities that 
are not clinically significant 
o For AEs occurring after the first FT538 infusion: 
− If recovery to baseline is not observed by Day 8, the scheduled Day 8 FT538 
infusion could be skipped. 
− If recovery to baseline is observed by Day 15, the scheduled Day 15 FT538 
infusion may be administered. 
− If recovery to baseline is not observed by Day 15, the scheduled Day 15 
FT538 infusion will be skipped. 
o For AEs occurring after the second FT538 infusion, if recovery to baseline is not 
observed by Day 15, the scheduled FT538 infusion will be skipped. 


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• If a Grade 3 hematologic AE that is not a DLT is observed, then FT538 dosing will 
continue according to schedule and without dose modification. 
Additional modifications to the FT538 dosing schedule, including dosing delays, 
will be based on consultation between the investigator and the principle 
investigator. (Note: Given the extremely high incidence of febrile neutropenia is 
patients with relapsed/refractory AML, febrile neutropenia will not be recorded as 
a hematologic AE; grade 3 febrile neutropenia falls into the same category as “Any 
other Grade 3 non-hematologic AE” per the table in section 6.3.1)  
 
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 
7.1 Infusion Related Reaction Associated with FT538 
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 FT538 
administration is described below. 
If Grade 4 Infusion-Related Reaction (Life-threatening consequences; urgent 
intervention indicated): 
Stop FT538 administration. Do not restart. 
The volume of FT538 administered prior to the infusion-related reaction must be 
documented; retain any remaining product and contact Dr. Maakaron 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 FT538 administration. 
• Manage symptoms, e.g., with antihistamines, antipyretics and analgesics, 
according to standard institutional practice standards. 
• Resume FT538 administration only upon complete resolution of the infusion-
related reaction and at the discretion of the Investigator. Given that FT538 
administration may involve single or multiple bags depending on the total 
planned dose and accounting for the stability of FT538 post-thaw, FT538 


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administration may continue following resolution to a Grade 1 infusion-related 
reactions as follows: 
If single-bag FT538 dosing: 
• No additional FT538 may be administered. 
• The volume of FT538 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 FT538 that was not 
administered from the bag during which the infusion-related reaction 
occurred. 
If multiple-bag FT538 dosing: 
• The volume of FT538 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 FT538 bags was planned, they may be thawed and 
administered. 
• Additional bags beyond what was originally planned may not be 
administered to make up for FT538 that was not administered from the bag 
during which the infusion-related reaction occurred. 
7.2 DMSO Related Risks 
FT538 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. It is 
recommended patients receive IV hydration with normal saline (NS) 250 ml bolus 
before and 250 ml bolus after FT538 administration to reduce the potential risks 
associated with DMSO. 
7.3 Infection 
FT538 is cell therapy of human origin. During processing, the cells are in contact 
with reagents of animal origin, and FT538 has a final formulation which contains 
albumin (human). As with any product of human and/or animal origin, transmission 
of infectious disease and/or disease agents by known or unknown agents may 
occur. FT538 has been extensively tested to minimize the potential risk of disease 
transmission. However, these measures do not completely eliminate the risk. For 


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some infectious agents, there are no routine tests to predict or prevent disease 
transmission (AABB 2016).   
7.4 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 in the clinical 
laboratory, 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 Table 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 deviation. 
 
Management of CRS should follow the recommended management algorithm 
provided in Table 4 (Neelapu 2018) and/or institutional practice. 
 
Table 4: 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. 


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Table 4: Recommendations for the Management of Cytokine Release Syndrome 
Grade 
Sign/Symptom  Management 
• 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 
• 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. 
Source: Neelapu et al. 2018; Actemra USPI 


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7.5 Neurotoxicity 
Neurotoxicity must be monitored at the time points specified in the Section 8 using 
the ASTCT guidelines for grading ICANS (Table 10; Lee et al. 2019) based on the 
ICE score. 
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 
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 
 
 




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Table 6:  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 7  
• 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  
• 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 8 
• 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 7  
• Stage ≥3 papilloedema, with a CSF opening pressure ≥20 mmHg or cerebral oedema, should 
be treated as per algorithm in Table 8 
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. 


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Table 7: 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  
• 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. 
 
 
 
 


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Table 8: 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 6)  
• 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  
• 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. 
7.6 Acute Graft-versus-Host Disease 
Because FT538 is an allogeneic immune effector cell product, there is a potential 
risk of GvHD even though allogeneic NK-cell therapies have not been associated 
with GvHD. (Veluchamy 2017). 
 
Acute GvHD assessments will be performed with assignment of the overall 
severity based on the CIBMTR acute GvHD grading scale (Table 9). 
Management of GvHD should be done in accordance with local institutional 
practice. 


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Acute GvHD will be assessed according to criteria established by the CIBMTR 
Scale (Table 9). 
 
Management of GvHD should be done in accordance with local institutional 
practice. 
 
Table 9: GVHD Grading and Staging  
Source: https://www.cibmtr.org/manuals/fim/1/en/topic/f2100-q131-233, assessed Oct 20, 2020. 
Extent of Organ Involvement 
Stage 
Skin 
Liver 
Gut 
1 
Rash on <25% of skin1 
Bilirubin 2-3 
mg/dl2 
Diarrhea > 500 ml/day3 or persistent 
nausea4 
Pediatric: 280-555 ml/m2/day or 10-19.9 
mL/kg/day 
2 
Rash on 25-50% of skin 
Bilirubin 3-6 
mg/dl 
Diarrhea >1000 ml/day 
Pediatric: 556-833 ml/m2/day or 20-30 
mL/kg/day 
3 
Rash on >50% of skin 
Bilirubin 6-15 
mg/dl 
Diarrhea >1500 ml/day 
Pediatric: >833 ml/m2/day or > 30 
mL/kg/day 
4 
Generalized erythroderma with 
bullous formation 
Bilirubin >15 
mg/dl 
Severe abdominal pain, with or without 
ileus, and / or grossly blood stool 
Grade5 
I 
Stage 1-2 
None 
None 
II 
Stage 3 
Stage 1 
Stage 1 
III 
— 
Stage 2-3 
Stages 2-4 
IV6 
Stage 4 
Stage 4 
— 
1 Use “Rule of Nines” (see Percent Body Surfaces table below) or burn chart to determine extent of rash. 
2 Range given as total bilirubin. Downgrade one stage if an additional cause of elevated bilirubin has been 
documented. 
3 Volume of diarrhea applies to adults. For pediatric patients, the volume of diarrhea should be based on body 
surface area. Downgrade one stage if an additional cause of diarrhea has been documented. 
4 Persistent nausea with or without histologic evidence of GVHD in the stomach or duodenum. 
5 Criteria for grading given as minimum degree of organ involvement required to confer that grade. 
6 Grade IV may also include lesser organ involvement with an extreme decrease in performance status 
7.7 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 autologous stem cell transplant is 
low. TLS symptoms include nausea, vomiting, diarrhea, muscle cramps or 


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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. 
7.8 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.  
7.9 Immunogenicity 
It is possible that FT538 may induce an immune response, which may manifest 
only through laboratory assessments, or may manifest clinically, e.g., as infusion-
related reactions with varying degrees of severity, including serious life-threatening 
anaphylactic reactions. AEs arising from FT538 immunogenicity will be managed 
per institutional practice.   
 
 


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8 
Schedule of Treatment, Tests, and Procedures 
“Clinic visits” may be done by a virtual visit or by phone, email, or text to assess general 
status, review lab results, and any ongoing adverse events. 
 
A minimum of 48 hour must separate the last dose of FLU and the FT538 infusion. 
There is no Day 0 in this treatment schema. 
 
A ± 1 Day window is permitted for the FT538 infusion to permit some flexibility of 
scheduling for individual patients. 
 
A ± 1 Day window is permitted for visits until the End of Treatment (EOT) assessment; 
however, whenever feasible do not shift subsequent future time points off of the 
targeted day.  
 
The End of Treatment assessment occurs no sooner than Day 29 (+3 days) as this is 
coincides with the end of DLT period.  
 
After Day 29, follow-up assessments are associated with the closest standard of care 
visit. The Day 42 follow-up is the final monitoring for excessive toxicity. 
 
In addition, targeted days may be altered as clinically appropriate. 


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8.1 Required Clinical Care Evaluations 
Bold – investigational agent 
treatment day 
Screening / 
Baseline 
Day 
-6 
Day 
-5 
Day  
-4  
Day 
-3 
Day 
-2 
Day 
1 
Day 
2 
Day 
3 
Day 
8 
Day 
15 
Day 
22 
 
Day 29 
EOT/ end 
of DLT 
 
Day 42 
(~end of 
SR period) 
3, 6, 9, and 12 
months from 1st  
FT538 infusion7 
Light – Daratumumab 
Bold shade – FT-538 
Consent 
X1 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Screening Assessment 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Brief Medical Assessment 
 
 
X 
 
 
 
X 
X 
 
X 
X 
X 
X 
 
 
Medical History 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Concomitant Medications10 
X 
 
X 
 
 
 
X 
 
X 
 
 
 
X 
 
 
Assess Venous Access 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical Exam 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
 
 
 
X 
Daratumumab 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Fludarabine 
 
X 
X 
X 
X 
X 
 
 
 
 
 
 
 
 
 
Cytoxan 
 
 
 
X 
X 
 
 
 
 
 
 
 
 
 
 
FT-538 
 
 
 
 
 
 
X 
 
 
X 
X 
 
 
 
 
Prophylaxis for Herpes Zoster 
Reactivation 
X (start per 
Section 6.1) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
ICANS 
(neurotoxicity)6 
monitoring – refer to Section 
7.5 
 
 
 
 
 
 
X 
X 
 
X 
X 
X 
X 
 
X 
KPS or Lansky Play score 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Weight 
X 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Height 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vitals and Pulse Oximetry 
X 
 
X 
 
 
 
X5 
X 
X 
X5 
X5 
X5 
X 
 
 
Toxicity Assessment in person
or patient reported and survival
status 
X 
 
X 
 
 
 
X 
X 
 
X 
X 
X 
X 
X 
X 
CBC, diff, plt 
X 
 
X 
 
 
 
X 
X 
 
X 
X 
X 
X 
X 
X 
Basic metabolic panel (BMP)1 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
Comprehensive 
metabolic 
panel (CMP)2 plus mg, phos 
X9 
 
X 
 
 
 
X 
 
 
X 
X 
X 
X 
X 
X 
eGFR 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urine or serum pregnancy test
for WOCBP3 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
If CRS is suspected or 
diagnosed 
 
 
 
 
 
 
X 
 
 
If patient develops neurotoxicity 
 
 
 
 
 
 
X11 
 
 
Disease staging8 
X 
 
 
 
 
 
 
 
 
 
 
X† 
 
 
Per SOC 
Bone marrow aspirate 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
CXR or chest CT scan  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Bold – investigational agent 
treatment day 
Screening / 
Baseline 
Day 
-6 
Day 
-5 
Day  
-4  
Day 
-3 
Day 
-2 
Day 
1 
Day 
2 
Day 
3 
Day 
8 
Day 
15 
Day 
22 
 
Day 29 
EOT/ end 
of DLT 
 
Day 42 
(~end of 
SR period) 
3, 6, 9, and 12 
months from 1st  
FT538 infusion7 
Light – Daratumumab 
Bold shade – FT-538 
PFTs4 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
LVEF by echo or MUGA 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SOC of assessment for history 
or suspected CNS involvement 
per Section 4.3.7 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 
basic metabolic panel consists of BUN, creatinine, calcium, glucose, lytes (CO2, Cl, Na, K)  
2 
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 
3 
women of child bearing potential – negative test must be obtained within 14 days prior to dose of daratumumab 
4 
pulmonary function testing required only if symptomatic or prior known impairment 
5 
Vital signs (temperature, systolic and diastolic blood pressure, heart rate, and respiration rate) are performed in association with the FT538 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 FT538. 
6 
If on a treatment day, assess 2-4 hours post treatment. 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 7.5. In addition, quantitative testing in blood for HHV6 and HHV7 in the context of neurotoxicity 
should be done.  
7 
Long-term follow-up continues for up to 15 years  
8 
BM aspirate/biopsy with flow, cytogenetics, NGS, and targeted molecular diagnostics. At time of each SOC BM bx collect research related aspirate sample in a green top tube – to TTL 
† BM aspirate and biopsy for response assessment should be performed on day 25 +/- 4 days. 
9 
Labs for eligibility per Section 4.2.4 must be done within 14 days prior to daratumumab. 
10  Hydroxyurea as used in the study is considered supportive care per Section 6.4, not as an anti-cancer agent  
11  ICANS assessments will only be required in the follow up period if clinically indicated, and may be discontinued upon patient’s return to baseline.  
 
 
 
 
 


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8.2 Research Related Tests and Procedures 
 
Baseline 
prior to 
study 
treatment   
Prior to 
DARA 
D-5 
During FT538/DARA 
Day 22 
End of treatment 
Visit (end of DLT 
period)  
Day 29 
End of excess 
toxicity period  
~Day 42 
3, 6, 9 and 12 
months from 1st dose 
of FT538 at time of 
SOC visit 
Prior to 
FT538 
#1 Day 1 
Day 2 
Day 3 
Prior to 
FT538 #2 
Day 8 
Prior to 
FT538 #3 
Day 15 
 
 
 
 
ferritin, CRP (to hospital lab 
charge to research)1 
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 tubes2 
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 (10 mL) 
One 10 ml green top tube2 30 (± 
5) minutes post FT538 infusion 
end 
 
 
X (post 
FT538) 
 
 
X (post 
FT538) 
X (post 
FT538) 
 
 
 
 
One 10 ml green top tube2 
 
 
 
X 
X 
 
 
 
 
 
 
Baseline 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 
 
 
 
 
 
 
 
 
 
 
Safety follow-up:  
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 (at 3, 6, and 12 
months only) 
At time of each bone marrow 
biopsy and/or aspirate, collect 
aspirate sample in a green top 
tube for research 
X 
 
 
 
X3 
 
 
X4 
 
 
X 
PRA anti-HLA antibodies  
one 10 ml red top (to hospital lab 
charge to research) 
X 
 
 
 
 
 
 
 
X 
 
 
Note: enrollment to this study is for patients 50 kg or greater. Adjustment to research blood volumes (weight based) is not required for pediatric patients. 
1 - refer to Section 8.1 and Section 7.4 for at the time CRS is suspected and if definitive diagnosis is made 
2 - At TTL: PBMCs are isolated from the heparin/green tube for PCR testing by Fate.  
3 - ±1 day, must follow FT538 infusion                                                                                                 4- BM biopsy for disease assessment to occur on day 25±4 days.  


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All research samples go to the Masonic Cancer Center’s Translational Therapy Lab (TTL) 
except for the baseline and Day 29 sample for ferritin and CRP testing and the pre- and 
post- PRA anti-HLA antibodies samples which are charged to research but run in the 
treatment center’s clinical lab.  
 
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, 
research samples may be collected at up to 3 extra 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.  
 
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. 
 
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).  
 
Any remaining PBMC will be cryopreserved in 10% DMSO and stored in liquid nitrogen for 
future testing, if the patient agreed to future storage at the time of initial consent. 
9 
Study Agents 
9.1 FT538 
FT538 is an investigational product and can only be used and administered under an 
FDA-approved protocol. For the purposes of this study FT538 is provided by Fate 
Therapeutics.  
9.1.1 Availability  
FT538 will be supplied by Fate Therapeutics for the purpose of this study. 


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9.1.2 Product Labelling 
FT538 labeling will include product name, volume, manufacturer, date of manufacture, 
Product Lot #, Bag ID #, and amount of VC. The label will also contain the following 
statement: “Caution: New Drug – Limited by United States Law to Investigational Use.” 
9.1.3 Storage  
FT538 is stored at the University of Minnesota Molecular and Cellular Therapeutics 
(MCT).  
 
FT538 must be stored in the vapor phase of liquid nitrogen (VPLN2) at ≤ -150°C, in a 
continuously temperature-monitored and alarmed VPLN2 freezer in a controlled-
access room with limited personnel access. Temperature excursions up to -135°C for 
10 minutes due to normal equipment use (e.g., opening and closing of the storage unit) 
are allowed.  
9.1.4 How Provided 
The formulated drug product is aseptically filled into pre-sterilized, single-use 
cryopreservation bags.  
9.1.5 Route of Administration 
FT538 is thawed and administered as an IV infusion via gravity. The following are 
acceptable forms of IV access in order of preference: 
1. Central venous catheter (CVC; e.g., Hickman) 
− Do not use implanted ports. 
2. Non-valved peripherally inserted central catheter (PICC) 
3. Large-bore (18-gauge) straight IV needle 
9.1.6 Potential Toxicities 
Refer to Section 7 for potential toxicities. 
 
Refer to the current FT538 Investigator Brochure for additional information.  
9.2 Daratumumab 
9.2.1 
Other names 
DARZALEX FASPRO™ (daratumumab and hyaluronidase-fihj) injection 
9.2.2 
Description 
DARZALEX FASPRO is a combination of daratumumab, a CD38-directed cytolytic 
antibody, and hyaluronidase, an endoglycosidase 


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9.2.3 
FDA Approved Indications 
DARZALEX FASPRO is approved for the treatment of adult patients with multiple 
myeloma (April 2020). 
9.2.4 
Availability  
A commercial formulation of daratumumab is purchased through the site’s 
Investigational Pharmacy for this study. 
9.2.5 
How Supplied and Storage 
DARZALEX FASPRO (daratumumab and hyaluronidase-fihj) injection is a sterile, 
preservative-free, colorless to yellow, and clear to opalescent solution for 
subcutaneous use supplied as individually packaged single-dose vials providing 1,800 
mg of daratumumab and 30,000 units of hyaluronidase per 15 mL (NDC 57894-503-
01). 
 
Store DARZALEX FASPRO vials in a refrigerator at 2ºC to 8ºC (36ºF to 46ºF) in the 
original carton to protect from light. 
 
Do not freeze or shake. 
9.2.6 
Preparation and Administration 
DARZALEX FASPRO is ready to use. 
• Remove the DARZALEX FASPRO vial from refrigerated storage [2°C to 8°C 
(36°F to 46°F)] and equilibrate to ambient temperature [15°C to 30°C (59°F to 
86°F)]. Store the unpunctured vial at ambient temperature and ambient light for 
a maximum of 24 hours. Keep out of direct sunlight. Do not shake. 
• Withdraw 15 mL from the vial into a syringe. 
• DARZALEX FASPRO is compatible with polypropylene or polyethylene syringe 
material; polypropylene, polyethylene, or polyvinyl chloride (PVC) subcutaneous 
infusion sets; and stainless steel transfer and injection needles. Use the product 
immediately. 
• 
After the solution of DARZALEX FASPRO is withdrawn into the syringe, replace 
the transfer needle with a syringe closing cap. Label the syringe appropriately 
to include the route of administration per institutional standards. Label the 
syringe with the peel-off label. 
• 
To avoid needle clogging, attach the hypodermic injection needle or 
subcutaneous infusion set to the syringe immediately prior to injection. 
• 
Parenteral drug products should be inspected visually for particulate matter and 
discoloration prior to administration, whenever solution and container permit. Do 
not use if opaque particles, discoloration or other foreign particles are present. 


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Storage of prepared syringe: 
• 
If the syringe containing DARZALEX FASPRO is not used immediately, store 
the DARZALEX FASPRO solution for up to 4 hours at ambient temperature and 
ambient light. Discard after 4 hours, if not used. 
Administration: 
• 
Inject 15 mL DARZALEX FASPRO into the subcutaneous tissue of the abdomen 
approximately 3 inches [7.5 cm] to the right or left of the navel over 
approximately 3-5 minutes. No data are available on performing the injection at 
other sites of the body. 
• 
Rotate injection sites for successive injections. 
• 
Never inject DARZALEX FASPRO into areas where the skin is red, bruised, 
tender, hard or areas where there are scars. 
• 
Pause or slow down delivery rate if the patient experiences pain. In the event 
pain is not alleviated by pausing or slowing down delivery rate, a second 
injection site may be chosen on the opposite side of the abdomen to deliver the 
remainder of the dose. 
• 
During treatment with DARZALEX FASPRO, do not administer other 
medications for subcutaneous use at the same site as DARZALEX FASPRO. 
9.2.7 
Potential Toxicities 
Warnings and Precautions:  
• Hypersensitivity and Other Administration Reactions: Permanently discontinue 
DARZALEX FASPRO for life-threatening reactions.  
• Neutropenia: Monitor complete blood cell counts periodically during treatment. 
Monitor patients with neutropenia for signs of infection. Consider withholding 
DARZALEX FASPRO to allow recovery of neutrophils.  
• Thrombocytopenia: Monitor complete blood cell counts periodically during 
treatment. Consider withholding DARZALEX FASPRO to allow recovery of 
platelets.  
• Embryo-Fetal Toxicity: Can cause fetal harm. Advise pregnant women of the 
potential risk to a fetus and advise females of reproductive potential to use 
effective contraception. Males and females should use effective contraception 
for at least 3 months after the last dose of drug. 
• Interference with cross-matching and red blood cell antibody screening: Type 
and screen patients prior to starting treatment. Inform blood banks that a patient 
has received DARZALEX FASPRO.  
 
Potential Risks: 
May be serious 
• Serious allergic reactions and other severe injection-related reactions. 


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• Injection site reactions 
• Decrease in blood counts 
• Changes in blood type testing for up to 6 months after last dose. 
The most common side effect when used as monotherapy included cold-like 
symptoms (upper respiratory infection). 
10 Adverse Event Monitoring, Documentation, and Reporting 
For the purposes of the study the FT538 and daratumumab are considered investigational 
products. 
 
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_v5_Q
uick_Reference_5x7.pdf) 
 
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).  
 


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Table 10: 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. 
 
Suspected Adverse Reaction: Any adverse event for which there is a reasonable 
possibility that the drug caused the adverse event. For the purposes of IND safety 
reporting, ‘reasonable possibility’ means there is evidence to suggest a causal 
relationship between the drug and the adverse event. A suspected adverse reaction 
implies a lesser degree of certainty about causality than an adverse reaction. 
 
Adverse Reaction:  Any adverse event caused by a drug. Adverse reactions are a 
subset of all suspected adverse reactions where there is reason to conclude that the 
drug caused the event. 
 


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Suspected Unexpected Serious Adverse Reaction (SUSAR): Any adverse event 
meeting that meets the definition of serious for which there is a reasonable possibility 
that the drug caused the adverse event and it meets the definition of unexpected.  
 
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 
• A persistent or significant incapacity or substantial disruption of the ability to 
conduct normal life functions 
• A congenital anomaly/birth defect 
• An important medical event 
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.  
 
Note: refer to the current FT538 Investigator Brochure for expected adverse events. 
For DARZALEX FASPRO™ the current USPI for expected adverse events.  
 
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 
10.2 AE Monitoring and Event Documentation Requirements 
Adverse event documentation for the purposes of this study will focus on events felt to 
be related to FT538, daratumumab, or events that cannot be attributed to other causes 
(i.e., disease under treatment, co-morbidities). Adverse events can be observed in 
person, abstracted from the medical record or patient reported. 
 


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Between the time of consent signing and the start of daratumumab, only events directly 
related to the study and result in the inability to begin study treatment are documented. 
Refer to Section 5.3 for handling of patients unable to begin study treatment.   
 
Monitoring for adverse events begins with the first dose of fludarabine on day -6. 
Frequent monitoring continues through the DLT period until Day 42 or 28 days after 
the last dose of FT538, whichever is later, based on the definition of excessive toxicity 
(stopping rules (SRs)). Once beyond the SR period, 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 FT538 will be documented upon 
knowledge. 
 
Adverse event documentation for the purposes of this study will focus on  
• expected toxicities felt to be related to daratumumab 
• expected toxicities felt to be related to the FT538  
• events meeting the definition of a DLT or excessive toxicity per Section 10.4 
• any event meeting the definition of serious, regardless of attribution 
• unexpected adverse events that cannot be attributed to the disease under treatment  
 
For the purposes of this study, adverse event documentation requirements in OnCore 
will be based on grade, expectedness and relationship to the investigational product 
(FT538, daratumumab): 
 
 
Exceptions to AE Documentation: Laboratory abnormalities (e.g., clinical chemistry, 
hematology, and urinalysis) without clinical significance are not recorded as AEs or 
SAEs with the exception of abnormalities that meet the definition of DLT per Section 
6.3.1. Other abnormal assessments (e.g., vital signs, ECG, X-rays) that are not 
associated with signs or are considered of no clinical significance do not need to be 
recorded unless they are a dose limiting toxicity.  
 
Clinically significant is defined as requiring medical or surgical intervention or leading to 
a study treatment delay or discontinuation. Any laboratory or other assessments 
meeting the definition of clinically significant must be recorded as an AE, as well as an 
 
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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SAE, if applicable. Electrolyte replacement and similar routine supportive care is 
excluded from AE reporting unless it meets the definition of a DLT. 
10.3 SAE Documentation and Reporting 
Any event meeting the definition of an SAE must be documented using the MCC 
SAE Report Form, save for subject death due to disease (see section 10.5) 
10.4 Dose Limiting Toxicity and Excessive Toxicity (Stopping Rule Events) 
Documentation and Reporting Requirements 
All patients are monitored for dose limiting toxicity (DLT) and excessive toxicity (early 
stopping events). Refer to Section 6.3.1 and Section 6.3.2 for definitions. 
 
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 10.3. 
10.5 Documentation of Death and Reporting Requirements 
Deaths during the treatment and follow-up period that are not due to AML will be 
recorded as an SAE and reported per Section 10.6. Deaths due to patient’s underlying 
disease need not be recorded as SAEs, but should be recorded as a grade 5 neoplasm 
in the AE log.  
 
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. 
 
 


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10.6 Expedited MCC Reporting Requirements  
As the study sponsor, the Masonic Cancer Center has the following expedited reporting 
responsibilities: 
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 
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 not related to primary 
malignancy; 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 Fate 
Therapeutics within 
1 business day of 
FDA reporting 
pv@fatetherapeutic
s.com 
 
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 
Fate 
Therapeutics 
Suspected Unexpected Serious Adverse Reactions 
(SUSARs) 
Within 3 business days of 
knowledge 
MCC SAE Report 
Form  
Fate Therapeutics at 
pv@fatetherapeutics.
com 
All other SAE’s 
Within 5 business days of 
knowledge 


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Center of Excellence for HIPAA Data) apply to OnCore databases. The informatics 
team grants the IRB approved study team members access to data. 
 
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/dsmp  
 
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. 
 
IND Annual Reports 
In accordance with regulation 21 CFR § 312.33, the IND S/I (Dr. Maakaron) 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 


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Therapeutics. Additional annual reporting requirements are found in the FDA 
Acknowledgment of Receipt of IND.  
 
11.4 Site Monitoring 
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 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.  
 
In addition, the Clinical Trials Office (CTO) will keep a master log in OnCore of all 
patients participating in the study with sufficient information to allow retrieval of the 
medical records for that patient.  
 
Please contact the CTO before destroying any study related records. 
12 Statistical Considerations  
12.1 Study Design, Objectives and Endpoints  
This is a Phase I study of FT538 for the treatment of patients with relapsed/refractory 
CD38 expressing hematological malignancies. The primary endpoint is the maximum 
tolerated dose (MTD) of FT538 when given in combination with daratumumab. 
 
The primary analysis will be intent-to-treat in that all patients receiving the 1st infusion 
of FT538 will be evaluable for toxicity and efficacy. Patients who discontinue therapy 
prior to infusion #1 will be replaced. We expect that the number of patients coming off 
therapy prior to infusion #1 will be minimal.  
 
There are 5 potential dose levels defined for Phase I. The trial will be conducted with 
no intra-patient escalation. The starting dose will be 1x108 FT538 cells with a safety 
dose of 5x107 FT538 cells. The subsequent planned cohorts will be 3x108 FT538 cells, 


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1x109 FT538 cells and 1.5 x109 FT538 cells (Table 1). Given that little to no toxicity is 
expected, the MTD will be determined using an adaptation of the continual 
reassessment method (CRM) (O’Quigley, 1996) starting with 1 patient cohorts.  
 
Table 1. FT538 Dose Level and Schedule 
Dose Level 
Treatment Plan for FT538 
-1 
5 x 107 cells on Day 1, Day 8 and Day 15 
1 (start) 
1 × 108 cells on Day 1, Day 8 and Day 15 
2 
3 × 108 cells on Day 1, Day 8 and Day 15 
3 
1 × 109 cells on Day 1, Day 8 and Day 15 
4 
1.5 × 109 cells on Day 1, Day 8 and Day 15 
 
Phase I will be conducted in two consecutive stages (non-CRM and CRM). A minimum 
of 28 days must separate each cohort. Within a 3 patient cohort, a minimum of 14 days 
must separate the 1st and 2nd patients. All patients are assessed for Dose Limiting 
Toxicity (DLT) as defined in the schema and Section 6.3.1. 
 
STAGE 1 STEP 1 Fast-track design (1 patient per dose cohort) 
Start at Dose Level 1 (DL1), enroll 1 patient per dose cohort separated by 28 days 
(DLT period) until the:  
• 1st pre-defined adverse event defined as any Grade 3 non-hematologic AE 
within 72 hours of a FT538 infusion  
• and the patient completes the 28 day DLT period with no DLT- Activate Stage 
1 Step 2 
OR  
• 1st DLT event within 28 days after the 1st dose of FT538 as defined in the 
Schema and in Section 6.3.1 - Activate Stage 2 (Stage 1 Step 2 is not used)  
OR 
• 10 patients are treated at the Dose Level 4 (This completes enrollment - 
Stage 1 Step 2 and Stage 2 are not used) 
• If the first patient at dose level 4 in stage 1 step 1 completes the DLT period 
with no pre-defined adverse events or DLT, successive subjects may enroll 
without staggering. 
 
STAGE 1 STEP 2 Expand current Dose Level and subsequent DLs to 3 patients 
The cohort size increases from 1 to 3 patients with 2 additional patients added to 
the current cohort. A minimum of 14 days must pass between the enrollment of 
the 1st and the 2nd patient in 3 patient cohorts and a minimum of 28 days 
between dose cohorts. Continue dose escalation until: 
• 1st DLT event as defined in the Schema and Section 6.3.1 - Activate Stage 2 
OR  


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• 10 patients are treated at the Dose Level 4 (This completes enrollment and 
Stage 2 is not used.) 
• For Dose Level 4 in stage 1, step 2, the second and third patients may enroll 
immediately but must complete their DLT period prior to enrolling the rest. If no 
DLT events occur within the monitoring period, successive subjects may enroll 
without staggering.  
 
 
 
Stage 2 is initiated at the 1st DLT. The study design changes to an application of the 
continual reassessment method (CRM) with an informative skeleton based on 
constrained maximum likelihood estimation (Iasonos & O'Quigley, 2012), (Iasonos & 
Ostrovnaya, 2011). Enrollment occurs in cohorts of three with a minimum of 14 days 
between the 1st and 2nd patient. Each new cohort of three patients is sequentially 
assigned to the most appropriate dose by the study statistician based on the updated 
toxicity probabilities once the 3rd patient in a cohort reaches Day 28 (end of DLT 
period). The goal will be to identify one of the 5 dose level strategies corresponding to 
the desired maximum toxicity rate of ≤25%. Given that we will have prior data once the 
CRM is initiated, no “skeleton” estimates are needed. The MTD will be identified by the 
minimum of the following criteria: (1) the total Stage 2 sample size of 25 is exhausted, 
(2) 10 consecutive patients are enrolled at the same dose. The function ‘crm’ from the 
R package ‘dfcrm’ will calculate posterior means of toxicity probabilities. Dose 
escalation of more than one level is not permitted with this design. 
12.2 Statistical Analysis 
The MTD will be determined by design. Response will be estimated with simple 
proportions and descriptive plots. The secondary endpoints of overall survival and 
progression-free survival will be estimated with Kaplan-Meier curves. Safety measures 
will be described with frequencies and proportions. Further descriptive statistics and 
plots such as boxplots, spaghetti plots and swimmer plots will be used to assess 
kinetics and other markers of efficacy and toxicity. 
12.3 Sample Size 
A maximum of 25 patients will be enrolled during Phase I with a target DLT rate of 
≤25%. Based on the simulations from Table 11, this should be sufficient and safe to 
define the MTD. Although complete skeleton estimates will not be determined until 
Stage 2, Table 11 is calculated based on hypothesized values. 
Table 11. Operating characteristics for Adaptive-CRM 
 
Cells/ dose 
Expected 
DLT, 
Expected 
SAE1,2 
Excessive DLT, Excessive SAE 
True 
Probability 
Prob. of 
dose3 
N4 
True 
Probability 
Probability 
of dose 
N 


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1. 
SAE’s without a DLT trigger step 2 in stage 1, DLT’s regardless of SAE’s trigger stage 2 
2. 
Expected/Excessive values are the hypothesized true values under the simulation 
3. 
Probability of dose chosen as the MTD using the Adaptive-CRM design 
4. 
The hypothesized number of patients enrolled at each dose during the trial under the assumed hypothesized 
“true” probabilities  
 
Enrollment will most likely include 17 patients or it could be as high as 25 patients if 
DLTs are encountered early.  
12.4 Monitoring Guidelines (Early Study Stopping Rules) 
Stopping Rule for Excessive DLT 
A stopping rule is in place during the Phase I study to stop the trial in case there are 
excessive DLTs as defined by updated posterior probabilities throughout the trial. At 
the end of the 28-day evaluation period after each cohort of patients is enrolled, new 
posterior probabilities will be calculated for each dose. The trial will be stopped if the 
posterior probability that the lowest dose is unacceptably toxic (> 25% of patients) is 
greater than 80%. (Zohar & Chevret, 2001)  
 
Stopping rules also are in place independent of dose escalation. (Ivanova, 2005).  
 
Infusion Related Reaction within 28 Days of the 1st Dose of FT538 
The goal is to construct a boundary based on Grade 4 infusion related reaction such 
that the probability of early stopping is at most 10% if the rate is equal to 5% and our 
sample size is at most 25. With these stipulations, the trial will be stopped and reviewed 
if 2/7, 3/16 or 4 patients have events by Day 28. If the true probability of infusion related 
toxicity is 20%, there is an 82% chance of triggering the monitoring boundary. If the 
sample size is only 17 patients, the probability of triggering the monitoring boundary 
drops to 67%. 
 
Aplasia at Day 42 (ANC <500) after at least 1 week of growth factor (i.e. G-CSF) 
with an aplastic bone marrow in the absence of leukemia (<5% cellularity) 
The goal is to construct a boundary based on aplasia such that the probability of early 
stopping is at most 10% if the rate is equal to 5% and our sample size is at most 25. 
With these stipulations, the trial will be stopped and reviewed if 2/7, 3/16 or 4   patients 
have events by Day 42. If the true probability of aplasia is 20%, there is an 82% chance 
5 x 107 cells (-1) 
1%, 2% 
0% 
0 
15%, 18% 
55% 
13 
1 × 108 cells (1) 
3%, 5% 
0% 
1 
25%, 29% 
37% 
9 
3 × 108 cells (2) 
6%, 8% 
1% 
3 
45%, 50% 
7% 
3 
1 × 109 cells (3) 
8%, 12% 
1% 
3 
60%, 66% 
1% 
0 
1.5 × 109 cells (4) 
10%, 15%  
98% 
10 
70%, 77% 
0% 
0 


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of triggering the monitoring boundary. If the sample size is only 17 patients, the 
probability of triggering the monitoring boundary drops to 67%. 
 
Early Death (Grade 5 Event) within 28 days after the last dose of FT538 
Enrollment will be suspended and reviewed by the study team with follow-up 
notification to the FDA and IRB of the findings before enrollment is restarted for any 
death within 28 days after the last dose of FT538 and not attributable to disease 
progression. At 25 patients, if the true probability of early death is 5%, there is a 93% 
chance of triggering the monitoring boundary. If the sample size is only 17 patients, the 
probability of triggering the monitoring boundary drops to 73%. 
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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14 References 
Actemra® (tocilizumab) injection, for intravenous or subcutaneous use [Prescribing Information]. 
San Francisco, CA. Genentech, Inc.; 2019. 
American Association of Blood Banks (AABB). Circular of Information for the Use of Human Blood 
and Blood Components. 2016. Available at: https://www.aabb.org/tm/coi/Documents/coi1017.pdf 
Arai S, Meagher R, Swearingen M, et al. Infusion of the allogeneic cell line NK-92 in patients with 
advanced renal cell cancer or melanoma: a phase I trial. Cytotherapy. 2008;10:625-32.  
Bachanova V, Cooley S, Defor TE, et al. Clearance of acute myeloid leukemia by haploidentical natural 
killer cells is improved using IL-2 diphtheria toxin fusion protein. Blood. 2014;123:3855-63.   
Bachanova V, Sarhan D, Defor TE, et al. Haploidentical natural killer cells induce remissions in non-
Hodgkin lymphoma patients with low levels of immune-suppressor cells. Cancer Immunol Immunother. 
2018;67:483-94.  
Bibeau F, Lopez-Crapez E, Di Fiore F, et al. Impact of FcRIIa-FcRIIIa polymorphisms and KRAS 
mutations on the clinical outcome of patients with metastatic colorectal cancer treated with cetuximab 
plus irinotecan. J Clin Oncol. 2009; 27:1122-29.  
Bjordahl R, Gaidarova S, Woan K, et al. Preclinical development of an off-the-shelf adoptive NK cell 
immunotherapy with targeted disruption of CD38 to prevent anti-CD38 antibody-mediated fratricide 
and enhance ADCC in multiple myeloma when combined with daratumumab. ASH Annual Meeting, 
abstract 133. 2019.  
Bride, K.L, Vincent TL, Im SY, et.al. 2018. Preclinical efficacy of daratumumab in T-cell acute 
lymphoblastic leukemia. Blood 131: 995-999. 
Brudno J, Kochenderfer J. Toxicities of chimeric antigen receptor T cells: recognition and 
management. Blood. 2016;127:3321-30. 
Buteyn N, Fatehchand, K, Santhanam R, et al. Anti-leukemic effects of all-trans retinoic acid in 
combination with  Daratumumab in acute myeloid leukemia. International Immunology, Vol. 30, No. 
8, pp. 375–383. 
Cartron G, Dacheux L, Salles G, et al. Therapeutic activity of humanized anti-CD20 monoclonal 
antibody and polymorphism in IgG Fc receptor FcRIIIa gene. Blood. 2002;99:754-8.  
Cichocki F, Woan W, Wu C-Y, et al. NK cells lacking CD38 are resistant to oxidative stress-induced 
death. ASH Annual Meeting, abstract 3215. 2019.  
Cooley S, He F, Bachanova V, et al. First-in-human trial of rhIL-15 and haploidentical natural killer cell 
therapy for advanced acute myeloid leukemia. Blood Advances. 2019;3:1970-80.  
Cyclophosphamide for Injection, USP [Prescribing Information]. Deerfield, IL. Baxter Healthcare 
Corporation; 2013.   
Dahlberg CI, Sarhan D, Chrobok M, et al. Natural killer cell-based therapies targeting cancer: possible 
strategies to gain and sustain anti-tumor activity. Front Immunol. 2015;6:605.  
Darzalex Fastpro™ (daratumumab and hyaluronidase-fihj) injection, for subcutaneous use 
[Prescribing Information]. Horsham, PA. Janssen Biotech, Inc, Issued 05/2020 assessed at 
http://www.janssenlabels.com/package-insert/product-monograph/prescribing-
information/DARZALEX+Faspro-pi.pdf September 28, 2020.  


CPRC #2020LS114:  FT538 with Daratumumab in Acute Myeloid Leukemia 
 
 
 
 
 
 
May 8, 2023 
Page 68 of 79 
MT2020-33 
Döhner H, Estey E, Grimwade D, et al. Diagnosis and management of AML in adults: 2017 ELN 
recommendations from an international expert panel. Blood. 2017;129:424-47.  
Dos Santos C, Xiaochuan S, Chenghui Z, et. al. Anti-Leukemic Activity of Daratumumab in Acute 
Myeloid Leukemia Cells and Patient-Derived Xenografts. Blood (2014) 124 (21): 2312. 
Drach J, McQuuen T, Engel H. Retinoic Acid-induced Expression of CD38 Antigen in Myeloid Cells 
Is Mediated through Retinoic Acid Receptor-α. Cancer Research: April 1994 
Volume 54, Issue 7. 
Ganzel, C., M. Kharit, C. Duksin, and J. M. Rowe. 2018. Daratumumab for relapsed/refractory 
Philadelphia-positive acute lymphoblastic leukemia. Haematologica 103: e489-e490. 
Geller MA, Cooley S, Judson PL, et al. A Phase II study of allogeneic natural killer cell therapy to treat 
patients with recurrent ovarian and breast cancer. Cytotherapy. 2011;13:98-107.   
Iasonos A. Ostrovnaya I. Estimating the dose-toxicity curve in completed phase I studies. Stat Med. 
2011 Jul 30;30(17):2117-29. doi: 10.1002/sim.4206. Epub 2011 Feb 22. 
Iasonos A, O'Quigley J. Interplay of priors and skeletons in two‑stage continual reassessment method. 
Volume31, Issue30 Special Issue: Papers from the 32nd Annual Conference of the International 
Society for Clinical Biostatistics 30 December 2012.Pages 4321-4336  
Iliopoulou EG, Kountourakis P, Karamouzis MV, et al. A Phase I trial of adoptive transfer of allogeneic 
natural killer cells in patients with advanced non-small cell lung cancer. Cancer Immunol Immunother. 
2010;59:1781-9.  
Jing Y, Ni Z, Wu J, et al. Identification of an ADAM17 cleavage region in human CD16 (FcγRIII) and 
the engineering of a non-cleavable version of the receptor in NK cells. PLoS One. 2015;10:e0121788.  
Kaspers, G. 2014. How I treat paediatric relapsed acute myeloid leukaemia. Br J Haematol 166: 636-
645.  
Kiessling R, Klein E, Wigzell H. "Natural" killer cells in the mouse. I. Cytotoxic cells with specificity for 
mouse Moloney leukemia cells. Specificity and distribution according to genotype. Eur J Immunol. 
1975;5:112-7.   
Lajoie L, Congy-Jolivet N, Bolzec A, et al. ADAM17-mediated shedding of FcgRIIIA on human NK 
cells: identification of the cleavage site and relationship with activation. J Immunol. 2014;192:741-51.  
Lee DW, Santomasso BD, Locke FL, et al. ASTCT consensus grading for cytokine release syndrome 
and neurological toxicity associated with immune effector cells. Biol Blood Marrow Transplant. 
2019;25:625-38.  
Malavasi F, Deaglio S, Funaro A, et al. Evolution and Function of the ADP Ribosyl Cyclase/CD38 
Gene Family in Physiology and Pathology. Physiol Rev 88: 841–886, 2008. 
Malmberg KJ, Carlsten M, Bjӧrklund A, et al. Natural killer cell-mediated immunosurveillance of human 
cancer. Semin Immunol. 2017;31:20-9.  
Miller JS, Soignier Y, Panoskaltsis-Mortari A, et al. Successful adoptive transfer and in vivo expansion 
of human haploidentical NK cells in patients with cancer. Blood. 2005;105;3051-7.  
Mistry, J, Hellmich C, Moore J. Daratumumab Inhibits AML Metabolic Capacity and Tumor Growth 
through Inhibition of CD38 Mediated Mitochondrial Transfer from Bone Marrow Stromal Cells to Blasts 
in the Leukemic Microenvironment. Blood (2019) 134 (Supplement_1): 1385. 


CPRC #2020LS114:  FT538 with Daratumumab in Acute Myeloid Leukemia 
 
 
 
 
 
 
May 8, 2023 
Page 69 of 79 
MT2020-33 
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;26:1789-96.  
Neelapu SS, Tummala S, Kebriaei P, et al. Chimeric antigen receptor T-cell therapy - assessment and 
management of toxicities. Nat Rev Clin Oncol. 2018;15:47-62.  
O'Quigley J, Shen LZ (1996). Continual Reassessment Method: a likelihood approach. Biometrics 52: 
395-405. 
Pui, C. H., W. L. Carroll, S. Meshinchi, and R. J. Arceci. 2011. Biology, risk stratification, and therapy 
of pediatric acute leukemias: an update. J Clin Oncol 29: 551-565. 
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;121:3599-608.  
Romee R, Rosario M, Berrien-Elliott MM, et al. Cytokine-induced memory-like natural killer cells exhibit 
enhanced responses against myeloid leukemia. Sci Transl Med. 2016;8:357ra123.  
Rubinstein MP, Kovar M, Purton JF, et al. Converting IL-15 to a superagonist by binding to soluble IL-
15Rα. PNAS. 2006;103:9661-71.  
Schuetz, C, Hoenig M, Moshous D, et.al. Daratumumab in life-threatening autoimmune hemolytic 
anemia following hematopoietic stem cell transplantation. Blood Adv 2: 2550-2553. 
Smyth MJ, Hayakawa Y, Takeda K, et al. New aspects of natural-killer-cell surveillance and therapy 
of cancer. Nat Rev Cancer. 2002;2:850-61.  
Stoklasek TA, Schluns KS, and Lefrançois L. Combined IL-15/IL-15Rα immunotherapy maximizes IL-
15 activity in vivo. J Immunol. 2006;177:6072-80. 
Tonn T, Schwabe D, Klingemann, et al. Treatment of patients with advanced cancer with the natural 
killer cell line NK-92. Cytotherapy. 2013;15:1563-70.  
Veluchamy JP, Kok N, van der Vliet HJ, et al. The rise of allogeneic natural killer cells as a platform 
for cancer immunotherapy: recent innovations and future developments. Front Immunol. 2017;8:631.  
Vogiatzi, F, Winterberg D, Lenk L, et.al. 2019. Daratumumab eradicates minimal residual disease in 
a preclinical model of pediatric T-cell acute lymphoblastic leukemia. Blood 134: 713-716. 
Waldhauer I, Steinle A. NK cells and cancer immunosurveillance. Oncogene. 2008;27:5932-43.  
Wang R, Jaw JJ, Stutzman NC, et al. Natural killer cell-produced IFN-γ and TNF-α induce target cell 
cytolysis through up-regulation of ICAM-1. J Leukoc Biol. 2012;91:299-309.   
Wang W, Erbe A, Hank J, et al. NK cell-mediated antibody-dependent cellular cytotoxicity in cancer 
immunotherapy. Front Immunol. 2015;6:368.  
Zhu H, Blum RH, Bjordahl R, et al. Pluripotent stem cell-derived NK cells with high-affinity 
noncleavable CD16a mediate improved antitumor activity. Blood 2020;135:399-410.    
Zohar S, Chevret S (2001). The continual reassessment method: comparison of Bayesian stopping 
rules for dose-ranging studies. Stat Med  20: 2827–43. 
Zwaan, C. M., Kolb E. A., Reinhardt D, et.al. Collaborative Efforts Driving Progress in Pediatric Acute 
Myeloid Leukemia. J Clin Oncol 33: 2949-2962. 
 


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Appendix I – Karnofsky Performance Status Scale/Lansky Play–Performance Scale 
 
Karnofsky Performance Status Scale Definitions Rating (%) Criteria 
Able to carry on normal activity and to work; 
no special care needed. 
100 
Normal no complaints; no evidence 
of disease.  
90 
Able to carry on normal activity; 
minor signs or symptoms of disease.  
80 
Normal activity with effort; some 
signs or symptoms of disease. 
Unable to work; able to live at home and care 
for most personal needs; varying amount of 
assistance needed. 
70 
Cares for self; unable to carry on 
normal activity or to do active work.  
60 
Requires occasional assistance, but 
is able to care for most of his 
personal needs. 
50 
Requires considerable assistance 
and frequent medical care. 
Unable to care for self; requires equivalent of 
institutional or hospital care; disease may be 
progressing rapidly. 
40 
Disabled; requires special care and 
assistance.  
30 
Severely disabled; hospital 
admission is indicated although 
death not imminent. 
20 
Very sick; hospital admission 
necessary; active supportive 
treatment necessary.  
10 
Moribund; fatal processes 
progressing rapidly 
0 
Dead 
 
Ref  Karnofsky DA, Abelmann WH, Craver LF, Burchenal JH. The Use of the Nitrogen Mustards in the Palliative 
Treatment of Carcinoma – with Particular Reference to Bronchogenic Carcinoma. Cancer. 1948;1(4):634-56. 
 
 


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Lansky Play-Performance Scale for Pediatric Patients (<16 years of age) 
Rating 
Description 
100 
Fully active, normal 
90 
Minor restrictions with strenuous physical activity 
80 
Active, but gets tired more quickly 
70 
Both greater restriction of, and less time spent in, active play 
60 
Up and around, but minimal active play; keeps busy with quieter activities 
50 
Lying around much of the day, but gets dressed; no active play; participates in all quiet play and 
activities 
40 
Mostly in bed; participates in quiet activities 
30 
Stuck in bed; needs help even for quiet play 
20 
Often sleeping; play is entirely limited to very passive activities 
10 
Does not play nor get out of bed 
0 
unresponsive 
Lansky SB, List MA, Lansky LL, Ritter-Sterr C, Miller DR. The measurement of performance in childhood cancer patients. 
Cancer. 1987 Oct 1;60(7):1651-6. 
 


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Appendix II – New York Heart Association (NYHA) Classification  
 
• 
Class I - No symptoms and no limitation in ordinary physical activity, e.g. shortness of breath 
when walking, climbing stairs etc. 
 
• 
Class II - Mild symptoms (mild shortness of breath and/or angina) and slight limitation during 
ordinary activity. 
 
• 
Class III - Marked limitation in activity due to symptoms, even during less-than-ordinary 
activity, e.g. walking short distances (20—100 m).Comfortable only at rest. 
 
• 
Class IV - Severe limitations. Experiences symptoms even while at rest. Mostly bedbound 
patients. 
 
 
 
 


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Appendix III - Risks Associated with Cyclophosphamide and Fludarabine 
 
Warnings and precautions ascribed to cyclophosphamide (CY) include: 
• 
Myelosuppression, immunosuppression, bone marrow failure, and infections (see next 
section) 
• 
Urinary tract and renal toxicity including hemorrhagic cystitis, pyelitis, ureteritis, and 
hematuria 
− Urinary tract obstructions must be corrected prior to receipt of CY. 
• 
Cardiotoxicity including myocarditis, myopericarditis, pericardial effusion, arrythmias, and 
congestive heart failure, which may be fatal 
− Study participants should be closely monitored, especially those with risk factors for 
cardiotoxicity or pre-existing cardiac disease. 
• 
Pulmonary toxicity including pneumonitis, pulmonary fibrosis, and pulmonary veno-
occlusive disease leading to respiratory failure 
• 
Secondary malignancies 
• 
Veno-occlusive liver disease, which can be fatal 
• 
Embryo-fetal toxicity 
Adverse reactions reported most often include neutropenia, febrile neutropenia, fever, alopecia, 
nausea, vomiting, and diarrhea. 
 
For the complete safety profile of CY, as well as information regarding supportive care and 
management of associated toxicities, refer to the current prescribing information (USPI). 
 
Warnings and precautions ascribed to fludarabine (FLU) include: 
• 
Severe bone marrow suppression, notably anemia, thrombocytopenia, and neutropenia 
(see below) 
• 
Transfusion-associated GvHD 
− Use only irradiated blood products for transfusions. 
• 
Severe CNS toxicity 
− Severe CNS toxicity was observed in patients treated at FLU doses of 96 mg/m2 for 
5-7 days. This toxicity was observed in ≤0.2% of patients treated at FLU doses of 25 
mg/m2 
− Infections 
• 
Renal insufficiency 
− The subject’s renal function should be monitored closely. 
• 
Tumor lysis syndrome (Section 7.7) 
• 
Embryo-fetal toxicity 
Adverse reactions occurring in >30% of subjects treated with FLU include myelosuppression 
(neutropenia, thrombocytopenia, and anemia), fever, infection, nausea and vomiting, fatigue, 
anorexia, cough, and weakness. 
 
For the complete safety profile of fludarabine, as well as information regarding supportive care and 
management of associated toxicities, refer to the current prescribing information (USPI). 
 


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Risks of CY/FLU when given with adoptive cell therapies: 
Some adoptive cell therapies delivered with supportive medications, such as CY and FLU for 
conditioning, 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 for the development of cytopenias and 
infections is strongly recommended. Management of cytopenias and infections, including transfusion 
support, antimicrobial prophylaxis, and use of growth factors, should be done in accordance with 
standard institutional practice.  
 
 
 


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Appendix IV – European LeukemiaNet (ELN) Response Criteria in Acute 
Myelogenous Leukemia 
 
The European LeukemiaNet (ELN) response criteria in acute myelogenous leukemia (AML)  
(Döhner 2017) are presented below.  
 
Method of Assessment  
Assessments of response in AML are performed primarily through analysis of bone marrow 
biopsy/aspirate and peripheral blood for enumeration of leukemic blasts. A single blood draw can be 
used for both hematology and disease response assessment if collected within 1 week of bone 
marrow biopsy with aspirate collection. Radiographic methods may be used to document 
extramedullary disease.  
 
Categories of response, death due to treatment failure, and relapse are summarized in AIV-Table 1. 
Peripheral blood collection for tumor response assessment should be done on the same day as 
other tumor response assessment procedures, e.g., bone marrow biopsy/aspirate.  
 
Testing for measurable residual disease (also known as minimal residual disease [MRD]) should be 
done per institutional practice.  If done, the method with which MRD was tested,  
e.g., multiparameter flow cytometry (MFC) or molecular-based methodologies, e.g., reverse 
transcription polymerase chain reaction (RT-PCR), should be documented in the electronic Case 
Report Form (eCRF). For subjects with extramedullary disease, the same radiographic method used 
to evaluate extramedullary disease at baseline should be used in subsequent tumor assessments. 
 


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AIV-Table 1 European LeukemiaNet Response Criteria in Acute Myelogenous 
Category 
Definition 
Comment 
Response 
Complete 
remission (CR) 
without minimal 
residual disease  
(CRMRD−) 
If studied pretreatment, CR with negativity for a genetic marker 
by RT-qPCR, or CR with negativity for MRD by MFC 
Sensitivities vary by marker tested, and by 
method used; therefore, test used and 
sensitivity of the assay should be reported; 
analyses should be done in experienced 
laboratories (centralized diagnostics) 
Complete 
remission (CR) 
• Bone marrow blasts <5%; 
• Absence of circulating blasts and blasts with Auer rods; 
• Absence of extramedullary disease; c 
• ANC ≥1.0 × 10e9/L (1000/µL); 
•Platelet count ≥100 × 10e9/L (100,000/µL) 
MRD+ or unknown 
CR with 
incomplete 
hematologic 
recovery (CRi) 
All CR criteria except for residual neutropenia (<1.0 × 10e9/L 
[1000/µL]) or thrombocytopenia (<100 × 10e9/L [100,000/µL]) 
 
Morphologic 
leukemia-free 
state (MLFS) 
• bone marrow blasts <5%; 
• Absence of blasts with Auer rods; 
• Absence of extramedullary disease; 
• No hematologic recovery required 
Marrow should not merely be "aplastic"; at 
least 200 cells should be enumerated or 
cellularity should be at least 10% 
Partial remission 
(PR) 
• All hematologic criteria of CR; 
• Decrease of bone marrow blast percentage to 5% to 25%; and 
• Decrease of pretreatment bone marrow blast percentage by at 
least 50% 
 
Stable disease 
(SD) 
Absence of CRMRD–, CR, CRi, PR, MLFS; and criteria for PD 
not met 
Period of stable disease should last at least 3 
months 
Progressive 
disease (PD) a, b 
Evidence for an increase in bone marrow blast percentage 
and/or absolute blast counts in blood. 
• 50% increase in marrow blasts over baseline (a minimum 
15% point increase is required in cases with <30% blasts at 
baseline; or persistent marrow blast percentage of >70%over 
at least 3 months; without at least a 100%improvement in 
ANC to an absolute level 
• (>0.5 × 10e9/L [500/ µL], and/or platelet count to >50 × 10e9/L 
[50,000/µL] non-transfused); or 
• >50% increase in peripheral blasts (WBC × %blasts) to >25 × 
10e9/L (>25,000/µL) (in the absence of differentiation 
syndrome); b or 
• New extramedullary disease c 
 
• A confirmatory marrow assessment to 
document blast increase may be performed 
after at least 4 weeks; the date of 
progression should then be defined as of 
the first observation date 
• "Progressive disease" is usually 
accompanied by a decline in ANC and 
platelets and increased transfusion 
requirement and decline in performance 
status or increase in symptoms.  In these 
cases, a marrow assessment, and 
radiographic evaluation of extramedullary 
disease if applicable, should be performed. 
Death Due to Treatment Failure 
Death in Aplasia 
• Deaths occurring ≥7 days following completion of initial 
treatment while cytopenic; 
• With an aplastic or hypoplastic bone marrow obtained within 7 
days of death, without evidence of persistent leukemia 
 
Death from 
indeterminate 
cause 
• Deaths occurring before completion of therapy, or <7 days 
following its completion; or 
• Deaths occurring ≥7 days following completion of initial therapy 
with no blasts in the blood, but no bone marrow examination 
available 
 
Relapse 
Hematologic 
relapse  
(after CRMRD-, 
CR, CRi) 
Bone marrow blasts ≥5%; or reappearance of blasts in the blood 
or development of exmedullary disease 
 


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AIV-Table 1 European LeukemiaNet Response Criteria in Acute Myelogenous 
Category 
Definition 
Comment 
Molecular relapse 
(after CRMRD-) 
If studied pretreatment, reoccurrence of MRD as assessed by 
RT–qPCR or by MFC 
Test applied, sensitivity of the assay, and 
cutoff values used must be reported; 
analyses should be done in experienced 
laboratories (centralized diagnostics) 
ANC, absolute neutrophil count; CR, complete remission; IDH, isocitrate dehydrogenase; MFC, multiparameterflow 
cytometry; MLFS, morphologic leukemia-free state; MRD, measurable residual disease (also known as minimal residual 
disease); RT-qPCR, real-time quantitative polymerase chain reaction; WBC, white blood cell. 
a “Progressive disease” is a new provisional category that is arbitrarily defined; the category aims at harmonizing the 
various definitions used in different clinical trials. 
b Certain targeted therapies, e.g., those inhibiting mutant IDH proteins may cause a differentiation syndrome, i.e., a 
transient increase in the percentage of bone marrow blasts and an absolute increase in blood blasts; in the setting of 
therapy with such compounds, an increase in blasts may not necessarily indicate PD. 
c Radiographic evaluation of extramedullary disease per investigator discretion. The same radiographic modality used to 
assess extramedullary disease at baseline should be used in subsequent tumor response assessments. 
Source: Döhner et al. 2017. 
 
 


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Appendix V: Initial Version of Study Schema, reflecting initial lymphodepletion 
regimen and daratumumab schedule, effective 27-Jan-2021 to 24-Nov-2022) 
There is no Day 0 in this treatment plan. 
 
                                                            DLT Assessment Period through Day 29         
         
                                                     
                                                                                                                                                                       Follow-up (months from Day 1) 
                                                                CY/FLU                                                                                                           end             end  
                            D                    D                      FT538  D       FT538  D       FT538 D                   of DLT       of SR                                  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study Day          -12                  -5      -4   -3           1      3            8    10          15    17                      29          42          3 mon  6 mon  9 mon  12 mon*      
No Day 0 
 
D:  DARZALEX FASPRO (1,800 mg daratumumab and 30,000 units hyaluronidase) administered subcutaneously (subQ) once a week 
for 5 doses on Day -12, Day -5, and Day +3, Day +10, Day+17  
 
CY/FLU: Cyclophosphamide 300 mg/m2 and fludarabine (FLU) 25 mg/m2 administered by IV infusion on 2 consecutive days (Day -4 
and Day -3)   
 
FT538: administered at assigned dose as an IV infusion via gravity on Day 1, Day 8, and Day 15  
 
All patients are monitored for dose limiting toxicities (DLTs) and unacceptable toxicity using early stopping rules (SRs)  
Day 29 end of dose limiting toxicity (DLT) assessment (DLTs are defined on the next page and in Section 6.3.1 of the protocol) 
Day 42 end monitoring for excessive toxicity (SR events are defined on the next page and in Section 6.3.2 of the protocol) 
 
*after the 12 month visit, follow-up transfers to the long-term follow-up (LTFU) study  
 
Up to 5 dose levels of FT538 will be tested (including, a DL -1, only used in event of DLT at DL 1): 
 
Dose Level (DL) Cohort 
FT538 cells/dose 
-1 
5 x 107  
1 (start) 
1 × 108  
2 
3 × 108  
3 
1 × 109  
4 
1.5 × 109  
Each DL Cohort is separated by a minimum of 28 days (end of the DLT period). A minimum of 14 days must pass between the enrollment 
of the 1st and the 2nd patient in 3 patient cohorts.  
 
 
 


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Page 79 of 79 
MT2020-33 
Appendix VI: Second Version of Study Schema, increased lymphodepletion with 
initial daratumumab schedule (Amended 11/24/2022, effective 11/24/2022 through 
03/20/2023)2 
There is no Day 0 in this treatment plan. 
 
                                                            DLT Assessment Period through Day 29         
         
                                                     
                                                                                                                                                                       
                                                                                                                                                              assess         end            end  
                           D                      CY    CY     FT538     D    FT538      D     FT538     D      response   of DLT     of SR      Follow-up (months from Day 1) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study Day          -12        -6    -5    -4   -3   -2     1          3         8        10         15    17          22              29         42         3 mon  6 mon  9 mon  12 mon*      
No Day 0 
 
D:  DARZALEX FASPRO (1,800 mg daratumumab and 30,000 units hyaluronidase) administered subcutaneously (subQ) once a week 
for 5 doses on Day -12, Day -5, and Day +3, Day +10, Day+17  
 
FLU: fludarabine (FLU) 25 mg/m2 administered by IV infusion for 5 consecutive days, Day -6, Day -5, Day -4, Day -3, and day -2. 
 
CY: Cyclophosphamide 60 mg/kg  administered by IV infusion for 2 consecutive days, Day -4 and Day -3   
 
FT538: administered at assigned dose as an IV infusion via gravity on Day 1, Day 8, and Day 15  
 
All patients are monitored for dose limiting toxicities (DLTs) and unacceptable toxicity using early stopping rules (SRs)  
Day 29 end of dose limiting toxicity (DLT) assessment (DLTs are defined on the next page and in Section 6.3.1 of the protocol) 
Day 42 end monitoring for excessive toxicity (SR events are defined on the next page and in Section 6.3.2 of the protocol) 
 
*after the 12 month visit, follow-up transfers to the long-term follow-up (LTFU) study  
 
Up to 5 dose levels of FT538 will be tested (including, a DL -1, only used in event of DLT at DL 1): 
 
Dose Level (DL) Cohort 
FT538 cells/dose 
-1 
5 x 107  
1 (start) 
1 × 108  
2 
3 × 108  
3 
1 × 109  
4 
1.5 × 109  
Each DL Cohort is separated by a minimum of 28 days (end of the DLT period). A minimum of 14 days must pass between the enrollment 
of the 1st and the 2nd patient in 3 patient cohorts.  
 
 
 
2 Subjects enrolled prior to 24-Nov-2022 received Cy-Flu lymphodepletion on day -4 and day -3 only. See Appendix V for previous 
schema. 
FLU 

ICF_001.pdf: 
 
Joseph Maakaron, MD - University of Minnesota//Number 2020LS114  
 
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Joseph Maakaron, MD 
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INFORMED CONSENT FORM 
AND AUTHORIZATION TO USE AND DISCLOSE PROTECTED HEALTH 
INFORMATION 
FOR ADULT PARTICIPANTS, AND PARTICIPANTS REACHING AGE OF 
MAJORITY 
 
Sponsor / Study Title: 
  
Joseph Maakaron, MD - University of Minnesota /  
MT2020-033: Study of FT538 in Combination with 
Daratumumab in Acute Myeloid Leukemia  
 
Protocol Number: 
 
2020LS114 (MT2020-33) 
 
Principal Investigator: 
(Study Doctor) 
 
Joseph Maakaron, MD 
  
Telephone: 
 
612-625-8942 
612-273-3000 (24-Hour) 
 
Address: 
University of Minnesota Medical Center, Fairview 
500 Harvard Street 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 FT538 
investigational cell product without cost for the purposes of this study. DARZALEX 
FASPRO™ (Daratumumab and hyaluronidase-fihj for subcutaneous injection) is 
provided without cost to you for the purpose of this study. 
 
Financial Interest Disclosure: This research is supported in part by Fate 
Therapeutics. The University of Minnesota has licensed certain aspects of FT538, the 
investigational cell product being tested in this study to Fate Therapeutics. The 
University of Minnesota may benefit financially if the investigational cell 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. 
 
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: 


 
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• 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 participants. 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 acute myeloid 
leukemia (AML) that has not responded to treatment (refractory) or returned after 
treatment (relapsed). To be eligible for this study your AML cells must show CD38, a 
protein “marker” present in some types of cancer. The FT538 and daratumumab given 
in this study target CD38 cells. If your CD38 status is not already known, it may be 
determined by reviewing bone marrow cells. 
 
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 of 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.   
• 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 study 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 supplying the investigational product FT538, the Advarra Institutional 


 
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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 
Your participation in this study will include:  
1. Screening tests and procedures to see if you are eligible to participate in the 
study 
2. A period in which you will receive the study drugs  
3. Follow-up tests and procedures to check on you after you receive the study 
drugs 
 
This study is testing up to 4 dose levels of FT538 (with one additional dose level in 
reserve if unacceptable side effects are seen in the lowest dose level). You are 
assigned to the currently enrolling FT538 dose level depending on when you enter the 
study. You will be told the dose level. All other study drugs are given at fixed doses 
(either a flat dose for everyone or adjusted based on your weight depending on how the 
study drug is usually given). 
 
Enrollment in the study is as follows: 
The study starts with 1 participant enrolled in a dose level starting at Dose Level 1, until 
any one of the following possible situations occurs which determines the design flow for 
the rest of the study enrollment (each bullet is its own path). The person providing you 
with the consent can let you know. Regardless of the path, enrollment in the study ends 
once 10 participants are treated at the same FT538 dose level. 
• Dose Level 4 (the highest dose level) is reached without an unacceptable side 
effect. Ten participants total are treated at this dose level and the study is done. 
• One of the participants experiences a pre-defined side effect, in this situation 2 
additional  participants are treated at the same dose level to see if the side effect 
was a fluke or it occurs in other participants. From this point forward, a minimum 
of 3  participants are enrolled in all future dose levels. Higher dose levels (up to 


 
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Dose Level 4) may be tested based on the side effects experienced by each 
group of 3. If an unacceptable side effect occurs (a long pre-defined list), the 
study again switches the dose level assignment design, and 10 participants are 
treated at the dose level considered the maximum tolerated dose and the study 
is done. 
• One of the participants experiences an unacceptable side effect, the study 
moves to enrollment to 3 participants per dose level and, based on the side 
effects experienced, future dose level assignment is based on the side effects of 
all participants enrolled to date. Each group of participants may be treated at the 
same dose level, a higher dose level or a lower dose level. Once 10 participants 
in a row are treated at the same dose level the study is done  
 
Regardless of the FT538 dose level assignment, the study activities are the same 
and all other study treatment is the same as reflected in the study calendar 
attached at the end of this document. However, this is just a plan and changes may 
be made on an individual participant basis as medically indicated as determined by the 
treating study doctor. 
 
Why is this research being done? 
The purpose of this study is to test the safety of FT538 at different doses in combination 
with daratumumab DARA and to gain some very preliminary disease response 
information. Up to 4 dose levels of FT538 will be tested in this study with 1 more dose 
level (Dose Level -1) in the unlikely event there is unacceptable side effects at Dose 
Level 1.  
 
FT538 is investigational, meaning that the United States Food and Drug Administration 
(US FDA) have not approved FT538 for the treatment of cancer or any other disease. It 
is only available through a research study such as this clinical trial. DARA when given 
as a subcutaneous injection (there also is an IV (into a vein) formulation available) only 
is approved for the treatment of Multiple Myeloma, another cancer of the blood. Its use 
in this study is investigational. 
 
FT538 is a type of cell product made up of “natural killer” or NK cells. NK cells are a 
type of immune blood cell that are known to attack cancer cells. The University of 
Minnesota has used NK cells obtained from a close relative (the donor) of the patient for 
close to 30 years. FT538 is produced by growing cells that come from a healthy human 
donor, not an embryo or fetus. The donor cells are treated 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 NK 
cells which, once ready as FT538, are frozen, stored, and shipped to the study site.  
 
FT538 is different from the NK cells in your body because the donor cells were changed 
through a process known as cell engineering. This type of cell engineering changes the 


 
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coded blueprint of cells, known as DNA, to change how the cells work in the body. 
Specifically three changes were made: 
• A special protein called “hnCD16” has been added to FT538 so it can attach to a 
type of anti-cancer drug called monoclonal antibodies to help NK cells target and 
kill cancer cells. 
• Another protein called an “IL-15/IL-15 receptor complex” has also been added to 
FT538 to help the NK cells stay alive 
• A protein called “CD38” was removed. CD38 is naturally present on NK cells.  
Removing CD38 allows certain monoclonal antibodies that target CD38, such as 
the 2nd study drug DARA, to kill the cancer cells, but not to kill FT538. 
 
The removal of CD38 may also increase the activity of NK cells. 
 
FT538 is considered a xenotransplantation product because it comes in contact with 
cells of animal origin during the manufacturing process. There are risks of taking a 
xenotransplantation product. Refer to the sections “What are the risks of being in this 
study? Is there any way being in this study could be bad for me (Detailed Risks) ?” for 
more information. 
 
DARA belongs to a class of drugs called monoclonal antibodies. Antibodies are large, 
Y-shaped proteins used by your body’s immune system to identify and remove anything 
that can be harmful to your body such as bacteria, viruses, and cancer cells. 
Monoclonal antibodies are antibodies that have been designed and engineered to 
attack a specific target, such as cancer cells. In this study, DARA plays two roles. The 
dose given before the CY/FLU may improve the effect of tamping down the immune 
system and may improve the NK cell survival.  
 
How long will I be in this study? 
After learning about this study and reading through this consent form, if you are 
interested in taking part, you will be asked to sign this consent form. This allows a 
review of your medical history and routine tests to make sure you are healthy enough to 
be in this study. This is called a screening period and may take up to 4 weeks. 
 
A single course of study treatment is given over approximately 5 weeks. Refer to the 
calendar attached as the last page of this document. Weekly visits and blood work are 
required for at least 2 weeks after your last dose of FT538. Additional visits may be 
required depending on your disease status and blood count recovery.  
 


 
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Follow-up for this study matches standard of care visits at 3 month, 6 month, 9 months 
and 12 month (1 year) from the 1st infusion of FT538. Routine information obtained from 
these visits (physical exam results, lab work, disease response) will be recorded in the 
study record. If at any time your disease worsens or your study doctor feels other 
treatment is needed, participation in this study will not affect those decisions; however, 
information will still be collected from your medical record as described above. 
 
Your direct participation in this research study is about 1 year; however, as part of this 
study you must agree to take part in a long-term follow-up (LTFU) study. FT538 is a 
genetically modified product and the US FDA requires additional follow-up in these 
products. After your participation ends in this research study, follow-up will continue at 
least once a year either in person, by mail, email, telephone or other method 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? 
Injection Related Reaction to the DARA: The change to a formulation that is given as 
an under the skin injection greatly reduced this risk as compared to the IV (into a vein) 
infusion. Approximately 10% of patients (1 in 10) has a mild to moderate injection 
reaction. Medications are given before and after the injection to reduce this risk. 
 
You will receive the common chemotherapy drugs, cyclophosphamide and fludarabine 
to lower your immune system and blood counts before starting FT538. This may 
increase your risk of infection and/or make you feel tired.  
 
Risks associated with FT538 are based on experience with other NK cell products and 
may include: 
 
Infusion Related Reaction is a potential risk FT538 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. 
 


 
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Cytokine release syndrome (CRS) is a serious and potentially life threatening 
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 participants 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 with AML or 
other cancers of the blood.   
 
What happens if I do not want to be in this research? 
You do not have to participate in this research. Your doctors will let you know of other 
treatment options. Your decision will not affect your future cancer care or your 
relationship with your doctor.  
 
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 study is only available at the University of Minnesota. Most likely 17  participants 
will be treated, but it could be as many as 25  participants if there are more side effects 
than expected. 
 
What happens if I say “Yes, I want to be in this research”? 
After signing the consent form, a screening period is done make sure you are healthy 
enough for the study and meet the enrollment criteria. This may take up to 28 days, but 
often is much shorter. 
 
Screening Period to confirm study eligibility 
The following procedures are part of the screening period: 
• Review of your medical history 
• Recording of your demographic information (such as age and ethnicity) 
• Assessment of your performance status (daily functioning)  
• Review of your current medications 
• Review of how you are feeling 


 
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• Complete physical examination, including height and weight 
• Vital signs (such as your blood pressure, heart rate, respiratory rate) 
• Electrocardiogram (ECG) to measure the electrical activity of your heart 
• Echocardiogram (ECHO), multiple-gated acquisition (MUGA) scan, or cardiac 
magnetic resonance imaging (MRI) to check your heart’s function 
• Blood samples (about 5 tablespoons) will be taken for the following reasons: 
− Check your state of health through standard laboratory tests  
− To see if you are pregnant if you are a woman who is able to have children. If 
you are pregnant or breastfeeding, you will not be able to participate in this 
study. 
− For infectious disease evaluation and viral monitoring, including HIV and 
hepatitis testing. Minnesota requires reporting of a positive test for HIV and 
some types of hepatitis, to the state health department. 
• Bone marrow biopsy with aspirate samples will be collected before you receive 
any study drugs. An aspirate is usually done together with a bone marrow biopsy 
and involves using a syringe to obtain a liquid bone marrow sample. 
− The biopsy/aspirate may be done at any time during screening - If you have 
had a bone marrow biopsy in the previous 28 days, this biopsy may be used 
for the pre-study treatment assessment. Your study doctor can let you know. 
− The sample will be used to assess the status of your cancer, provide 
information about your cancer cells, and may be used for additional research 
purposes. 
• Other tests and procedures may be done based on your individual medical 
situation. 
 
Study Treatment Overview: 
If you are eligible and still want to participate in this study you will receive the study 
drugs as described below.  
 
Please refer to the study calendar attached to this document for an overview of the 
study treatment plan. 
 
Note about Day numbering: this study mimics the day counting long established by 
hematologic treatments. FT538 is considered the primary study drug so the 1st dose is 
given on Day 1. Any treatment or activities before Day 1, are assigned a negative (Day-) 
number counting backwards from Day 1. For example, fludarabine is given on day -6, -
5, -4, -3, and -2, and cyclophosphamide is given on Day -4 and Day -3. The dose of 
DARA is given on Day -5, or 5 days before the 1st FT538. The study calendar attached 
to this document reflects this day counting method using Monday as the Day 1. 
 
There are windows built into the study plan in case of a holiday, bad weather or other 
reason the study treatment cannot be given or a follow-up visit needs to be changed. 
 


 
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Daratumumab (trade name DARZALEX FASPRO) or DARA for short is given as an 
under the skin (subcutaneous) injection near the belly button before the 1st dose of 
FT538. 
 
Fludarabine (FLU) chemotherapy is given over a five-day period in the outpatient clinic 
to improve the survival of the FT538 cells, as an intravenous (IV – into a vein) infusion. 
 
Cyclophosphamide (CY) chemotherapy is given to over a 2 day period in the 
outpatient clinic to improve the survival of the FT538 cells. Like fludarabine, 
cyclophosphamide is given as an intravenous (IV –into a vein) infusion.  
 
FT538 is given once a week for 3 weeks in a row as an intravenous (IV –into a vein) 
infusion. FT538 cells come in pre-dosed bags and depending on the dose you are 
assigned you will receive one or more bags. Each bag takes about 15 minutes to be 
infused. 
 
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 the dose of DARA, before and after each dose of 
FT538, and at each follow-up visit through the 12 month visit. Approximately 5 
tablespoons of blood will be collected at each time point. The 1st and the one at 4 weeks 
after the 1st dose of FT538 will be approximately 6 tablespoons as additional testing is 
done. During follow-up at Months 3, 6, 9, and 12 the amount of blood will be reduced to 
approximately 3 tablespoons of blood. 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 each FT538 infusion.  
 
Blood from the research samples will be tested and analyzed to look at your immune 
system and the effects of FT538. The testing may include testing using genetic markers 
to see how much and how long FT538 is present in your blood. This research will 
provide a better understanding of how FT538 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. 
 
Each time you have a bone marrow biopsy for your medical care through the 12 month 
study period, additional cells (aspirate) may be collected for research related testing; an 
aspirate will also be collected on your day +3 after receiving your first dose of FT538. In 
addition, if, at the time of going on study you had a recent bone marrow biopsy (within 28 
days), part of those stored (archived) samples will be made available for research 
purposes. 
 


 
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If any blood or bone marrow cells left over from the collections described above, the 
extra samples may be stored for additional future research related testing. This may 
include further tests about how FT538 works against cancer, or it may include research 
tests about other cancer treatment or prevention methods. This testing may include 
future genetic testing.  
 
Information obtained from the research samples will be used only for purposes of 
research and development. None of the research-related testing results will affect your 
care or your participation in this study. The research 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 bone marrow 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 bone marrow 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. 
 


 
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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. 
 
Alternative Treatments 
You do not have to be in this study to receive treatment for your AML. Your options may 
include: 
• Receiving treatment that is available without being a research study.  
• Participating in another study.  
• Getting no treatment.  If you decide that you don’t want any more active 
treatment, one of your options is called “comfort care”, also called palliative care.  
This type of care helps reduce pain, tiredness, appetite problems and other 
problems caused by the cancer. It does not treat the cancer directly, but instead 
tries to improve how you feel. Comfort care tries to keep you as active and 
comfortable as possible. If you think you might prefer comfort care, please 
discuss this with your family, friends and your regular doctor. 
 
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 study staff or your study 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 1st FT538 
dose, you are asked to maintain contact with your study doctor in case of side effects.  
 
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. 
 


 
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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 treatment on this study. 
 
Possible Risks of FT538  
This is one of the first time that FT538 has been given to people. The risks are not 
known at this time. The potential risks of receiving FT538 include those related to how 
FT538 may work in the body and how the body may react to FT538. The potential side 
effects listed below are based on laboratory studies and knowledge of similar cell 
therapy drugs. 
 
FT538 is stored in a solution containing dimethyl sulfoxide (or DMSO) and human 
albumin. Both of these ingredients are commonly used in cell therapies and may have 
risks in addition to those of the cell therapy itself.  
 
DMSO may cause side effects like: 
• Coughing 
• Chest tightness 
• Wheezing 
• Flushing  (redness), 
• Rash  
• Nausea 
• Vomiting  
• High or low blood pressure 
 
You will receive intravenous (IV - into a vein) fluids before and after the FT538 to lessen 
the risk of a reaction. 
 
Human albumin and other ingredients of animal origin are used to make FT538 
cells and may contain viruses that cause infection or disease. FT538 is tested to reduce 
the risk of certain viral infections. Allergic reactions may occur with human albumin. 
Symptoms could include: 
• Fever 
• Chill  
• Rash 
• Nausea 
• Vomiting  
• Fast heart rate 
• Low blood pressure 
 


 
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Other potential risks for FT538 related to how FT538 may work in the body are 
described below. 
 
Infusion-related or allergic reaction 
There is a potential risk for an allergic reaction which, may occur during the infusion 
(while the study drug is being given through your vein). This reaction could be mild (skin 
irritation/rash) to life-threatening (difficulty breathing/swelling of the face and throat). The 
study doctor will give you medications such as acetaminophen (Tylenol®) and 
diphenhydramine (Benadryl®) before receiving FT538 to lessen the risk of an infusion-
related or allergic reaction. 
 
You will be closely monitored during and after the infusion. If any sign of a reaction 
occurs, additional medications are given and the infusion stopped (and, if applicable, 
any remaining bags of cells not given). Additional FT538 doses may be given with 
adjustments to the pre-medications, or if a severe reaction, the FT538 will be 
permanently discontinued. 
 
Cytokine release syndrome 
Cytokine release syndrome (also called CRS) is a generalized inflammation response, 
which may be produced in the body with therapies that turn on the immune system, 
including immune cell therapies like FT538.  CRS symptoms are usually mild to 
moderate and include fever, nausea, chills, decreased blood pressure, increased heart 
rate, weakness, headache, rash, scratchy throat, and difficulty breathing.  However, in 
rare instances, patients can develop severe, even potentially life-threatening symptoms 
of CRS.  
 
Please seek treatment immediately and tell the study doctor or the study staff if you 
have any of these symptoms, or any other side effects, during the study. 
 
Tumor lysis syndrome 
Tumor lysis syndrome (also called TLS) can happen when cancer cells have broken 
down and byproducts of that breakdown have entered the bloodstream. Symptoms may 
include: 
• Weakness 
• Low blood pressure 
• Muscle cramps  
• Decreased urination 
 
TLS can lead to kidney damage and/or other organ damage. In addition to cancer 
treatment, many factors, including the type and extent of the cancer, as well as 
treatments given to an individual, can contribute to TLS. Let the study doctor know 
immediately if you develop these symptoms.   
 


 
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Effects on the nervous system 
Receipt of cell therapies may result in side effects involving the brain and other parts of 
the nervous system. Effects on the nervous system observed with other cell therapies 
include confusion, delirium (loss of contact with reality), and sometimes seizures and 
cerebral edema (swelling) that could lead to death. This has not been a common risk 
associated with NK-cell therapies. As a part of this study, frequent neurologic 
assessments will be done. 
 
Increased risk of infection 
Because FT538 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. FT538 has been extensively tested to reduce the risk of disease 
infection. However, these tests do not completely eliminate this risk. For some infectious 
agents, there are no routine tests to predict or prevent their presence. 
 
Graft-versus-host disease 
Because FT538 is created from the cells of a donor who is not related to the participant 
receiving FT538, there is a risk of a condition called graft-versus-host disease (also 
called GvHD). This is a condition where the donor’s immune cells (the graft) view the 
participant’s healthy cells (the host) as foreign, and attack and damage the healthy 
cells. GvHD may cause damage to several organs including the skin, liver, and the 
gastrointestinal tract. GvHD can be mild, moderate, or severe. In some cases, it can be 
life-threatening. Depending on the severity of GvHD, you may need medication 
designed to control the immune system to treat GvHD. The medication that may be 
needed to control the immune system to treat GvHD also could affect the effectiveness 
of FT538. 
 
Risks Related to Xenotransplantation Products 
FT538 is considered a xenotransplantation product because it comes in contact with 
cells of animal origin (mouse cell) during the manufacturing process. Risks of receiving 
a xenotransplantation product may include, but are not limited to, developing infections 
from agents that may be associated with cells of animal origin, transmitting these 
infectious agents to others, and the growth of tumors. The animal cells, which come into 
contact with the FT538 cells during the manufacturing process, originate from a master 
cell bank that has been extensively tested to reduce these risks. However, these tests 
do not completely eliminate this risk. The likelihood and timing for developing a 
condition or illness from xenotransplantation products is unknown. If you have any 
questions about the risks involved in receiving a xenotransplantation product, ask the 
study doctor or a member of the study staff. 
 


 
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Because FT538 is a xenotransplantation product, you are also expected to have certain 
responsibilities in the future. These future responsibilities may include, but are not 
limited to, having regular check-ups and telling your regular doctor or other healthcare 
providers about receiving a xenotransplantation product in the event of unexplained 
illnesses. You and your family members and intimate contacts should not donate blood, 
sperm, or other body fluids or tissues. If needed, ask the study doctor or a member of 
the study staff to help you discuss this with your family members and intimate contacts, 
or if you have any questions.  
 
Possible Risks of Daratumumab (DARA) 
In this study DARA is given as a subcutaneous (under the skin) injection that was 
developed to avoid the infusion related reactions experienced with DARA when given 
into a vein. The change to a formulation that is given as an under the skin injection 
greatly reduced this risk as compared to the IV (into a vein) infusion. Approximately 
10% of people (1 in 10) has a mild to moderate injection reaction. Medications are given 
before and after the injection to reduce this risk. 
 
Possible risks of DARA during and/or after an injection (occurs in about 1 in 10 people, 
less than 1 in 10 people had a severe reaction). Signs and symptoms included: 
• Shortness of breath or trouble breathing 
• Dizziness  
• Lightheadedness  
• Hypotension(low blood pressure) 
• Cough 
• Wheezing 
• Throat tightness 
• Runny or stuffy nose 
• Headache 
• Itching 
• Nausea 
• Vomiting 
• Chills or fever 
• Chest pain 
 
The most common side effects of DARA given as an under the skin injection include: 
• Cold-like symptoms (upper respiratory infection)  
• Changes in blood cell counts which may result in an increased risk of infection, 
bleeding/bruising and/or fatigue. 
 
Some people experience pain during the injection. If this occurs, the injection can be 
slowed or stopped. In addition, some people may have skin reactions at or near the 
injection site (local), site redness the most frequent reaction occurred in about 8 out of 
100 people.  


 
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Daratumumab can affect the results of blood tests to match your blood type. These 
changes can last up to 6 months after your final dose of daratumumab. Your blood type 
will be confirmed prior to receiving DARA. Tell all of your doctors that you are taking 
or received daratumumab before receiving blood transfusions. 
 
Daratumumab may cause rare and unexpected side effects other than those described 
here. Tell your study doctor if you have any unusual problems while receiving this study 
drug. 
 
Possible Risks of Cyclophosphamide and Fludarabine 
Both of these study drugs are commonly used as a cancer treatment or in preparation for 
a cell infusion (as in this study).  
 
The side effects are well known, although an unknown or serious side effect may occur 
in an individual patient. Very rarely a side effect is severe enough to prevent a patient 
from continuing with the planned research treatment or even be fatal. 
 
Cyclophosphamide (CY) 
Common Side Effects (occurring in more than 30 out of 100 participants) 
• Low blood counts: Your white and red 
blood cells and platelets may 
temporarily decrease.  This can put you 
at increased risk for infection, anemia, 
and/or bleeding. 
• Poor appetite 
• Nausea and vomiting (more common 
with larger doses) 
• Temporary hair loss  
• Discoloration of the skin or nails 
Less Common Side Effects (occurring in about 10-29 out of 100 participants) 
• Loss of fertility 
• Diarrhea 
• Mouth sores 
• Bladder problems and bleeding 
(hemorrhagic cystitis) 
 
Serious, but uncommon, side effects of CY include:  
• Increased risk of developing other cancers, such as bladder cancer, acute 
leukemia (a type of blood cancer), lymphoma (a type of lymph node cancer), 
thyroid cancer, and/or sarcoma (a type of cancer that can start in the soft tissue, 
bone, or other tissue).  
• Liver problems, which can be fatal 
• Heart failure, which can be fatal 
• Inflammation of the lung  
 
CY may cause rare and unexpected side effects other than those described here. Tell 
the study doctor if you have any unusual problems while receiving this study drug. 
 


 
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Fludarabine (FLU) 
Common Side Effects (occurring in more than 30 out of 100 participants) 
• Fever 
• Infection 
• Weakness 
• Cough 
• Nausea and vomiting 
• Poor appetite 
• Low blood counts.  Your white and red 
blood cells and platelets may 
temporarily decrease.  This can put you 
at increased risk for infection, anemia, 
and/or bleeding. 
Less Common Side Effects (occurring in about 10-29 out of 100 participants) 
• Chills 
• Fatigue 
• Pain 
• Sweating 
• Numbness and tingling of hands and 
feet 
• Shortness of breath (lung problems) 
• Diarrhea 
• Rash (skin reactions) 
• Swelling 
• Taste changes, metallic taste 
 
Serious, but uncommon, side effects of FLU include:  
• An increased risk of infection (such as herpes, fungal infection, and 
Pneumocystis carinii) due to suppression of the immune system   
• Severe side effects involving the brain and other parts of the nervous system, 
which were seen at doses higher than the dose you will receive in this study     
• Hemolytic anemia (destruction of red blood cells)   
• A rare condition called transfusion-associated graft-versus-host disease (also 
called GvHD), which occurs when immune cells in a blood transfusion attack 
cells in the body causing fever, rash, liver problems, and abdominal pain and 
diarrhea.  If you require a blood transfusion while on this study, you will receive 
only blood transfusions that have received radiation treatment to reduce the risk 
of transfusion-associated GvHD. 
• Tumor lysis syndrome (also called TLS) can happen when cancer cells have 
broken down and byproducts of that breakdown have entered the bloodstream. 
Symptoms may include weakness, low blood pressure, muscle cramps, and/or 
decreased urination. TLS can lead to kidney damage and/or other organ 
damage.  
You may receive allopurinol, an oral medication, beginning before the start of 
study treatment to reduce this risk.  
 
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. 


 
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• Bone Marrow Biopsy/Aspiration: Common side effects of a bone marrow 
biopsy/aspirate include pain, swelling, bleeding, and drainage from the biopsy 
site. Although less common, there is a risk of infection and abnormal wound 
healing following any biopsy. The study doctor will explain the details and risks of 
the biopsy procedure, which may vary depending on how the biopsy will be 
obtained. 
• 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 participant 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 participant 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 FT538 on an unborn baby or on sperm are not known. The risks of the 
other study drugs are known and some cause harm to an unborn baby. 
 
Women who are pregnant are not eligible to take part in this study.  
 
Females: Women of childbearing potential (WOCBP) must use a highly effective form 
of contraception from the screening visit until at least 12 months after the final dose of 
cyclophosphamide (CY), at least 4 months after the final dose of FT538, and at least 4 
months after the final dose of daratumumab, whichever is latest. 
 
Males: Men who are in this research study should not get a sexual partner pregnant. 
Males with a female partner of childbearing potential or a pregnant female partner must 
be sterile (biologically or surgically) or use a highly effective method of contraception 
from the screening visit until at least 14 months after the final dose of CY and at least 6 
months after the final dose of FT538, and at least 5 months after the final dose of 
daratumumab, whichever is latest. 
 
Acceptable methods of birth control for use in this study are: 
• Double barrier contraception 
• Inserted, injectable, transdermal, or combination oral contraceptive 
• A surgically sterile sexual partner 
• Abstinence. 


 
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If you or a female partner of a male participant become pregnant within 4 months after 
the last dose of FT538, it is important that you notify the study doctor or another study 
staff member. 
 
Will it cost me anything to participate in this research study? 
FT538 is provided at no cost by Fate Therapeutics for the purpose of this study. DARA 
is being provided at no cost by the study. The cost of processing and testing any 
samples collected for research is paid for by study funds. 
 
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 
CY/FLU, administration of all study drugs, medications given to prevent or treat side 
effects, clinic visits, hospitalization, routine medical care, all lab tests done for standard 
safety assessment, and assessments that are done for your medical care. You will 
continue to be responsible for any copays or deductibles associated with your 
insurance. 
 
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 and you are giving permission to any health care providers who are treating 
you to share your medical records with us.   
 


 
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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; 
• 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); 


 
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• 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. 
• Fate Therapeutics will receive copies of serious adverse events without direct 
identifiers and cumulative study patient data without direct patient identifiers. 
Some of the research samples will be batch analyzed by Fate, the results will be 
incorporated in to the overall study data to be correlated with clinical data. 
 
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 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.  
 


 
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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. 
 
Does my permission for making my health information available for use and 
sharing ever expire? 
No, there is no expiration date.  
 
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. 
 


 
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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. 
 
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 Participant                                                          Date 
 
__________________________________________ 
Printed Name of Participant 
 
WITNESS SIGNATURE FOR PARTICIPANTS WHO CANNOT READ  
The study participant has indicated that he/she is unable to read. This Authorization 
document has been read to the participant by a member of the study staff, discussed 
with the participant by a member of the study staff, and the participant has been given 
an opportunity to ask questions of the study staff.   
 
____________________________________ 
Printed Name of Impartial Witness  
 
____________________________________  
 
__________ 
Signature of Impartial Witness  
 
 
 
           Date 
 
FOR CHILDREN WHO BECOME ADULTS  
I have been told that my parents/legal guardian agreed to the use and disclosure of my 
Protected Health Information as outlined in this document. I have read and understand 
the information in this authorization. I have had an opportunity to ask questions and all 
of my questions have been answered to my satisfaction. I continue to authorize the use 
and disclosure of my Protected Health Information. I will receive a copy of this signed 
and dated authorization. 
__________________________________________      _______________ 
Signature of Participant                                                     Date 
 
__________________________________________ 
Printed Name of Participant 
 


 
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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 participants. 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 study 
doctor 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. 
 
An institutional review board (IRB) is an independent committee established to help 
protect the rights of research participants. If you have any questions about your rights 
as a research participant, and/or concerns or complaints regarding this research study, 
contact: 
 
• By mail:  
Study Subject Adviser 
Advarra IRB 
6100 Merriweather Dr., Suite 600 
Columbia, MD 21044 
• or call toll free:        877-992-4724 
• or by email:              adviser@advarra.com 
 
Please reference the number when contacting the Study Subject Adviser: Pro00055619. 
 


 
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To share feedback privately with the University of Minnesota HRPP about your research 
experience, call the Research Participants’ Advocate Line at 612-625-1650 (Toll Free: 
1-888-224-8636) or go to z.umn.edu/participants. 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, as 
required by U.S. Law. This Web site will not include information that can identify you. At 
most, the Web site will include a summary of the results. You can 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 
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 at the contact information located on page 1 of this form. 
 
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 Research Samples for Future Research: 
Once the research associated with this study is completed, there may be some leftover 
blood and cells from the samples collected for research purposes. With your permission 
we would like to store them 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 


 
Joseph Maakaron, MD - University of Minnesota//Number 2020LS114  
 
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Joseph Maakaron, MD 
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Affix Patient Label Here 
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 in this consent: 
 
_____ (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 
 


 
Joseph Maakaron, MD - University of Minnesota//Number 2020LS114  
 
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Joseph Maakaron, MD 
Advarra IRB Approved Version 23 May 2023 
 
 
 
Affix Patient Label Here 
Signature Block for Capable Adult: 
Your signature documents your permission to take part in this research study. You will 
be provided with a copy of this signed and dated document. 
 
_______________________________________________      __________________ 
Signature of Participant                                                              Date 
 
_______________________________________________ 
Printed Name of Participant 
 
____________________________________________            __________________ 
Signature of Person Obtaining Consent                                     Date 
 
______________________________________________________ 
Printed Name of Person Obtaining Consent 
 
WITNESS SIGNATURE FOR PARTICIPANTS WHO CANNOT READ  
The study participant has indicated that he/she is unable to read. The consent 
document has been read to the participant by a member of the study staff, discussed 
with the participant by a member of the study staff, and the participant has been given 
an opportunity to ask questions of the study staff.   
 
 
________________________________________ 
Printed Name of Impartial Witness  
 
 
________________________________________ 
 
___________ 
Signature of Impartial Witness 
 
 
 
          Date  
 
FOR CHILDREN WHO BECOME ADULTS  
I have been told that my parent/legal guardian agreed for me to participate in this 
research study as a minor. I have read and understand the information in this informed 
consent document. I have had an opportunity to ask questions and all of my questions 
have been answered to my satisfaction. I voluntarily agree to continue to participate in 
this study until I decide otherwise. I do not give up any of my legal rights by signing and 
dating this consent document. I will receive a copy of this signed and dated consent 
document. 
 
________________________________________               
Participant’s Printed Name  
 
________________________________________ 
 
___________ 
Participant’s Signature 
 
 
 
 
 
Date 


 
Joseph Maakaron, MD - University of Minnesota//Number 2020LS114  
 
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Joseph Maakaron, MD 
Advarra IRB Approved Version 23 May 2023 
 
 
 
Affix Patient Label Here 
RESEARCH STUDY CALENDAR EXAMPLE 
Note about Day numbering: this study mimics the day counting long established by 
hematologic treatments. FT538 is considered the primary study drug so the 1st dose is given on 
Day 1. Any study treatment or activities before Day 1, are assigned a negative (Day-) number 
counting backwards from Day 1. For example, cyclophosphamide and fludarabine are given on 
Day -4 and Day -3 (the Thursday and Friday before the 1st FT538 on Monday). The dose of 
DARA is given on Day -5, or 5 days before the 1st FT538. The attached calendar reflects 
this day counting method. 
 
Follow-up continues with a clinic visit and bloodwork at approximately 3, 6, 9 and 12 
months after the 1st FT538 infusion. 
 
The 12 month visit is the end of study visit.  Follow-up transfers to the long-term follow-
up study as described in that consent form. 
Study Treatment Plan with FT538 given on Mondays 
Sun 
Mon 
Tue 
Wed  
Thu 
Fri 
Sat 
Day -8 
Day -7 
 
Day -6 
FLU 
Day -5 
DARA/FL
U 
Day -4 
CY/FLU 
Day -3 
CY/FLU 
Day -2 
FLU 
Day -1 
Day 1 
FT538 #1 
Day 2 
blood 
work 
Day 3 
bm 
aspirate 
Day 4 
Day 5 
Day 6 
Day 7 
Day 8 
FT538 #2 
Day 9 
Day 10 
 
Day 11 
Day 12 
Day 13 
Day 14 
Day 15 
FT538 #3 
Day 16 
Day 17 
 
Day 18 
Day 19 
Day 20 
Day 21 
Day 22 
Follow-up 
visit 
Day 23 
Day 24 
 
Day 25  
bm bx 
Day 26 
Day 27 
Day 28 
Day 29 
Follow-up 
visit  
Day 30 
Day 31 
Day 32 
Day 33 
Day 34 
Day 35 
Day 36 
Clinic visit 
if needed 
Day 37 
Day 38 
Day 39 
Day 40 
Day 41 
Day 42 
Day 43 
Follow-up 
visit or 
check-in