Phase I/II Clinical Trial of Daratumumab and Donor Lymphocyte Infusion in Patients With Relapsed Acute Myeloid Leukemia Post-Allogeneic Hematopoietic Stem Cell Transplant
Phase: PHASE1
Conditions: Minimal Residual Disease, Recurrent Acute Myeloid Leukemia With Myelodysplasia-Related Changes, Recurrent Adult Acute Myeloid Leukemia, Recurrent Childhood Acute Myeloid Leukemia
Sponsor: Sumithira Vasu

Date of protocol: 10/14/2020                                                    IRB Approval Date: 11/24/2020 
Version of protocol: 7 
IND number: 139015 
Institutional protocol number: OSU 17102 
1 
 
 
Phase I/II clinical trial of Daratumumab in patients with relapsed acute myeloid leukemia post-
allogeneic hematopoietic stem cell transplant. 
 
Principal Investigator: 
Sumithira Vasu MBBS, 
Associate Professor of Medicine, 
Division of Hematology, 
Medical Director, Stem Cell Therapy Lab, 
Blood and Marrow Transplantation Section, 
The Ohio State University Wexner Medical Center, 
B 310 Starling-Loving Hall, 
320 W 10th Avenue, 
Columbus, OH 43210 
PH: 614-293-8197 
Sumithira.Vasu@osumc.edu 
 
Drug and Funding Supporter  
Janssen Scientific Affairs, LLC is providing drug and funding support for this study. 
 
IND Sponsor:  
The Ohio State University  
 
 
 

Date of protocol: 10/14/2020                                                    IRB Approval Date: 11/24/2020 
Version of protocol: 7 
IND number: 139015 
Institutional protocol number: OSU 17102 
2 
 
1 Table of Contents 
2 
PROTOCOL SYNOPSIS ...................................................................................................................... 5 
3 
KEY ROLES ....................................................................................................................................... 13 
4 
INTRODUCTION .............................................................................................................................. 13 
4.1 
AML RELAPSE POST-TRANSPLANT ................................................................................... 13 
4.2 
ROLE OF DLI ............................................................................................................................ 13 
4.3 
PRECLINICAL DATA REGARDING DARATUMUMAB ..................................................... 13 
4.4 
RATIONALE FOR PROPOSED STUDY ................................................................................. 18 
5 
STUDY OBJECTIVES ....................................................................................................................... 19 
5.1 
PRIMARY OBJECTIVE ............................................................................................................ 19 
5.2 
SECONDARY OBJECTIVES .................................................................................................... 19 
5.3 
EXPLORATORY OBJECTIVES ............................................................................................... 19 
6 
STUDY ENPOINTS ........................................................................................................................... 19 
6.1 
PRIMARY ENDPOINT ............................................................................................................. 19 
6.2 
SECONDARY ENDPOINTS FOR PHASE II ........................................................................... 20 
6.3 
EXPLORATORY ENPOINTS FOR PHASE I AND II ............................................................. 20 
7 
STUDY DESIGN ................................................................................................................................ 21 
7.1 
OVERVIEW OF STUDY DESIGN ........................................................................................... 21 
7.2 
NUMBER OF PATIENTS .......................................................................................................... 22 
7.3 
DURATION OF STUDY ........................................................................................................... 23 
8 
STUDY POPULATION ..................................................................................................................... 23 
8.1 
INCLUSION CRITERIA ............................................................................................................ 23 
8.2 
EXCLUSION CRITERIA ........................................................................................................... 23 
9 
DARATUMUMAB ADMINISTRATION ......................................................................................... 24 
9.1 
Recommended Concomitant Medications .................................................................................. 24 
9.1.1 
Pre-infusion Medication ...................................................................................................... 24 
9.1.2 
Post-infusion Medication .................................................................................................... 24 
9.2 
DARATUMUMAB INFUSION RELATED REACTIONS ...................................................... 25 
9.3 
DONOR LYMPHOCYTE INFUSION....................................................................................... 25 
9.4 
CRITERIA TO BE MET BEFORE EACH DOSE OF DARATUMUMAB .............................. 25 
9.5 
Post-transplant Standard of care concomitant meds ................................................................... 25 
9.6 
DEFINITIONS OF DOSE LIMITING TOXICITY ................................................................... 25 

Date of protocol: 10/14/2020                                                    IRB Approval Date: 11/24/2020 
Version of protocol: 7 
IND number: 139015 
Institutional protocol number: OSU 17102 
3 
 
10 
MANAGEMENT OF CLINICAL EVENTS .................................................................................. 26 
10.1 
CYTOPENIAS ............................................................................................................................ 26 
10.2 
GRAFT VERSUS HOST DISEASE .......................................................................................... 26 
10.3 
OTHER CLINICAL EVENTS ................................................................................................... 26 
11 
DESCRIPTION OF INVESTIGATIONAL AGENT ..................................................................... 27 
11.1 
STORAGE, HANDLING AND ACCOUNTABILITY ............................................................. 27 
11.2 
Safety Information for Daratumumab ......................................................................................... 27 
12 
STUDY CONDUCT ....................................................................................................................... 28 
12.1 
STUDY PROCEDURES ............................................................................................................ 28 
12.1.1 
PHYSICAL EXAMINATION ............................................................................................ 28 
12.1.2 
LABORATORY EVALUATION ...................................................................................... 28 
12.1.3 
STUDY RELATED PROCEDURES AND STUDY CALENDAR ................................... 29 
12.2 
DISEASE ASSESSMENT TIMELINES .................................................................................... 32 
12.3 
COMPLETION OF TREATMENT ............................................................................................ 33 
12.4 
COMPLETION OF STUDY ...................................................................................................... 33 
12.5 
POST-TREATMENT FOLLOW-UP ASSESSMENTS ............................................................. 33 
12.6 
EXPECTED TIMELINES FOR RECRUITMENT, DATA REPORTING ................................ 33 
13 
ADVERSE EVENT MONITORING AND REPORTING ............................................................ 33 
13.1 
Individual Case Safety Report (ICSR) ........................................................................................ 34 
13.2 
Product Quality Complaint (PQC) .............................................................................................. 34 
13.3 
Serious Adverse Event (SAE) ..................................................................................................... 34 
13.3.1 
Hospitalization .................................................................................................................... 35 
13.3.2 
Life-Threatening Conditions ............................................................................................... 35 
http://www.Daratumumab.com/shared/product/Daratumumab/Daratumumab-prescribing-
information.pdf ................................................................................... Error! Bookmark not defined. 
13.4 
PREGNANCY ............................................................................................................................ 36 
13.5 
Maintenance of Safety Information ............................................................................................ 37 
13.6 
Procedures for Reporting Safety Data and Product Quality Complaints (PQCs) for J&J 
medicinal products to Janssen Scientific Affairs, LLC ........................................................................... 37 
13.6.1 
SAEs and Special Reporting Situations .............................................................................. 37 
13.6.2 
Non-Serious AEs ................................................................................................................ 38 
13.6.3 
PQC Reporting .................................................................................................................... 38 
14 
STUDY-SPECIFIC COMMITTEES .............................................................................................. 40 

Date of protocol: 10/14/2020                                                    IRB Approval Date: 11/24/2020 
Version of protocol: 7 
IND number: 139015 
Institutional protocol number: OSU 17102 
4 
 
14.1 
DOSE ESCALATION AND ADVERSE EVENT MONITORING CALLS ............................. 40 
15 
DATA HANDLING AND RECORD-KEEPING .......................................................................... 40 
15.1 
ECRFs ......................................................................................................................................... 40 
16 
STATISTICAL CONSIDERATIONS ............................................................................................ 40 
16.1 
Study endpoints: .......................................................................................................................... 42 
16.2 
Analysis methods: ....................................................................................................................... 42 
16.3 
SAFETY ANALYSIS ................................................................................................................. 43 
17 
QUALITY CONTROL AND QUALITY ASSURANCE .............................................................. 43 
18 
References ....................................................................................................................................... 45 
19 
Appendix ......................................................................................................................................... 47 
 
 
 
 

Date of protocol: 10/14/2020                                                    IRB Approval Date: 11/24/2020 
Version of protocol: 7 
IND number: 139015 
Institutional protocol number: OSU 17102 
5 
 
2 PROTOCOL SYNOPSIS 
Title 
Phase I/II clinical trial of Daratumumab in patients with 
relapsed acute myeloid leukemia post-allogeneic 
hematopoietic stem cell transplant. 
Protocol Short Title 
Daratumumab in post-transplant relapse  
Name of Drug 
Daratumumab 
Study Rationale 
1. IFN-γ promotes graft-versus-leukemia effects 
without directly interacting with leukemia cells in 
mice after allogeneic hematopoietic cell 
transplantation.  
2. Endogenous IFN-gamma levels are elevated in 
post-transplant patients post-conditioning, 
infections, GVHD, and during hematopoietic 
regeneration.  
3. We hypothesize that (i) IFN-gamma levels will be 
higher in post-transplant patients than healthy 
donors (ii) combination of Daratumumab and 
endogenous IFN-gamma will mediate antileukemic 
efficacy post-transplant (iii) the combination of 
Dara and donor lymphocytes will provide potent 
effectors, recruit effectors to marrow and mediate 
GVL. 
Treatment Duration 
8 weeks; Daratumumab may be continued beyond 8 
weeks if clinical benefit is observed up to 12 months.  
Dosing Schedule  
Weekly Dara for 8 doses 
Route 
Intravenous 
Age range 
≥ 18 years 
Study Duration 
10 months to 3.5 years for phase I; 24 months for phase II. 
Sample size 
8-40 patients for Phase I; 25 patients for phase II 
Inclusion Criteria 
1. Patients ≥ 18 years  
2. AML relapse following Allo-HSCT 
(Morphological relapse, or MRD positive verified 
by flow cytometry, cytogenetics, and molecular 
mutations)  

Date of protocol: 10/14/2020                                                    IRB Approval Date: 11/24/2020 
Version of protocol: 7 
IND number: 139015 
Institutional protocol number: OSU 17102 
6 
 
3. For patients in Dose level 1 (Daratumumab only), 
relapsed refractory AML patients who have 
previously not received an allogeneic HCT are 
eligible.  
4. Patients with R/R AML must not be candidates for 
available therapies known to be effective for 
treatment of their AML. 
5. MDS transformed to AML following Allo-HCT 
6. Patients who received a 10/10 HLA-matched 
allogeneic HCT either from sibling donors or 
unrelated donors or atleast a 5/10 haploidentical 
transplant for dose levels needing DLI 
7. Engraftment must have occurred as defined by 
platelet (PLT) count > 20,000/µL and ANC ≥ 0.5 
8. ECOG performance status < 3 
9. Creatinine clearance > 40 ml/min (Calculated or 
measured)  
10.  Aspartate aminotransferase (AST) < 3 x upper 
limit of normal (ULN), alanine aminotransferase 
(ALT) < 3 x ULN, and total bilirubin < 1.5 x ULN 
11. Off calcineurin inhibitors for at least 2 weeks 
12. Prednisone dose ≤ 20 mg/day  
13. Patients with proliferative disease can be 
cytoreduced with cytotoxic chemotherapy at 
investigator’s discretion, but there should be at 
least a 14 day window between start of 
cytoreductive therapy and start of Daratumumab 
14. Blast count ˂20K/day (hydrea use is allowed) 
15. Female patients of childbearing potential who are 
sexually active must be willing to use an effective 
barrier method of birth control to avoid pregnancy 
during the study and for a minimum of 3 months 
after stopping study treatment 
16. Male patients must agree to not donate sperm and 
if sexually active with partners of childbearing 
potential must be willing to use an effective barrier 

Date of protocol: 10/14/2020                                                    IRB Approval Date: 11/24/2020 
Version of protocol: 7 
IND number: 139015 
Institutional protocol number: OSU 17102 
7 
 
method of birth control to avoid pregnancy during 
the study and for a minimum of 3 months after 
stopping study treatment 
Exclusion Criteria 
1. No demonstrable evidence of donor chimerism (˂ 
55% donor CD3 or CD33 chimerism) 
2. Patients with a molecular mutation without 
chromosomal abnormalities or declining 
chimerisms (MRD status must be verified by 
surface marker and mutational analyses) 
3. Active graft-versus-host disease (GVHD) grades 
I-IV; prior acute GVHD could have occurred but 
resolved at time of initiation of Daratumumab  
4.  Extensive chronic GVHD requiring ongoing 
immunosuppression with calcineurin inhibitors or 
more than 20 mg of prednisone 
5. Patients with FLT3+ AML or blast crisis CML 
who have not yet received post-transplant TKI 
therapy 
6. Active CNS or testicular disease 
7. Subject is: seropositive for human 
immunodeficiency virus (HIV); seropositive for 
hepatitis B (defined by a positive test for hepatitis 
B surface antigen [HBsAg]). Subjects with 
resolved infection (ie, subjects who are HBsAg 
negative but positive for antibodies to hepatitis B 
core antigen [anti-HBc] and/or antibodies to 
hepatitis B surface antigen [anti-HBs]) must be 
screened using real-time polymerase chain 
reaction (PCR) measurement of hepatitis B virus 
(HBV) DNA levels. Those who are PCR positive 
will be excluded. EXCEPTION: Subjects with 
serologic findings suggestive of HBV vaccination 
(anti-HBs positivity as the only serologic marker) 
AND a known history of prior HBV vaccination, 
do not need to be tested for HBV DNA by PCR.; 
seropositive for hepatitis C (except in the setting 
of a sustained virologic response [SVR], defined 
as aviremia at least 12 weeks after completion of 
antiviral therapy). 

Date of protocol: 10/14/2020                                                    IRB Approval Date: 11/24/2020 
Version of protocol: 7 
IND number: 139015 
Institutional protocol number: OSU 17102 
8 
 
8. Patients must not have chronic obstructive 
pulmonary disease with a forced expiratory 
volume in 1 second (FEV1) < 50% of predicted 
normal.  FEV1 is required for patients suspected 
of having chronic obstructive pulmonary disease 
and are not eligible if FEV1 is < 50% of predicted 
normal. 
9. Patients must not have moderate or severe 
persistent asthma within the past 2 years and must 
not have currently uncontrolled asthma of any 
classification. 
10. History of grade IV anaphylactic reaction to 
monoclonal antibody therapy  
11. Active autoimmune disease prior to transplant 
12. Pregnancy 
13. Female patients of childbearing potential who are 
sexually active and unwilling to use an effective 
barrier method of birth control to avoid pregnancy 
during the study and for a minimum of 3 months 
after study treatment 
14. Male patients who wish to donate sperm or with 
partners of childbearing potential who are 
sexually active and unwilling to use an effective 
barrier method of birth control to avoid pregnancy 
during the study and for a minimum of 3 months 
after study treatment 
15. Concurrent use of any other investigational drugs 
Study Design 
1. Phase I study (3+3 study design) with the 
following dose levels: 
For related sibling donors: 
a. Dose level 1: Dara 16mg/kg 
b. Dose level 2: Dara 16mg/kg + DLI at 
weeks 3-5: 1x10e6 CD3/kg 
c. Dose level 3: Dara 16mg/kg + DLI at 
weeks 3-5: 1x10e7 CD3/kg 
For unrelated donors: 

Date of protocol: 10/14/2020                                                    IRB Approval Date: 11/24/2020 
Version of protocol: 7 
IND number: 139015 
Institutional protocol number: OSU 17102 
9 
 
d. Dose level 1: Dara 16mg/kg  
e. Dose level 2: Dara 16mg/kg + DLI at 
weeks 3-5: 1x10e5 CD3/kg  
f. Dose level 3: Dara 16mg/kg + DLI at 
weeks 3-5: 1x10e6 CD3/kg 
 
For haploidentical donors: 
g. Dose level 1: Dara 16mg/kg  
h. Dose level 2: Dara 16mg/kg + DLI at 
weeks 3-5: 1x10e4 CD3/kg  
i. 
Dose level 3: Dara 16mg/kg + DLI at 
weeks 3-5: 1x10e5 CD3/kg 
2. Phase II study with maximal tolerated dose as 
established for both related and unrelated donors. 
The MTD for the DLI may be different for related 
and unrelated donors.  
Study logistics 
1. Identify patient with suspected relapse  
2. Trial discussed, consent obtained and bone marrow 
performed 
3. If MRD positive or morphologic relapse, stop 
immunosuppression within a week of biopsy 
results 
4. If no evidence of GVHD in 2 weeks after stopping 
immunosuppression, start Daratumumab.  
5. Daratumumab may be given as outpatient or 
inpatient depending on treating physician 
discretion. 
6. Patient will be seen prior to every Daratumumab 
dose and assessment for GVHD will be done 
7. Plan bone marrow biopsy after doses 3 and before 
dose 4. 
8. Administer DLI between weeks 3-5.  
9. Resume weekly Dara weeks 6-8 

Date of protocol: 10/14/2020                                                    IRB Approval Date: 11/24/2020 
Version of protocol: 7 
IND number: 139015 
Institutional protocol number: OSU 17102 
10 
 
10. Bone marrow biopsy after week 8  
Study Objectives – Phase I 
Primary Objectives: 
1. Phase I: 
To determine the maximum tolerated dose (MTD) of 
Daratumumab and escalating doses of donor 
lymphocyte infusions (DLI) in post-HCT patients with 
relapsed AML and MDS transformed to AML. 
2. Phase II: 
To evaluate overall response rate to Daratumumab and 
DLI by week 8 in patients with post-HCT relapsed 
AML and MDS 
Secondary Objectives: 
1. To assess overall response rates in MRD positive 
patients and in patients with overt morphological 
relapse  
2. To assess MRD conversion rates from MRD 
positive to MRD negative.  
3. To determine the post-relapse 6-month OS rates 
of patients with relapsed AML and MDS 
following allo-HSCT who are treated with 
Daratumumab 
4. To determine the rates of GVHD (both grades II-
IV and III-IV) and autoimmune side effects of 
Daratumumab by 3 months. 
5. To determine the post-relapse 6-month PFS rates 
of patients with relapsed AML and MDS 
following allo-HSCT who are treated with 
Daratumumab 
Safety Assessment  
Physical examination, electrocardiogram (ECG), clinical 
laboratory tests (hematology, blood chemistries, 
urinalysis, prothrombin time [PT], activated partial 
thromboplastin time [APTT]), anti-drug antibody (ADA), 
cytokine/inflammatory factor levels, vital signs, and 
adverse event/toxicity assessment.  
Efficacy Assessment 
Standard response assessment as defined for AML, 
duration of response, and overall survival/PFS. 

Date of protocol: 10/14/2020                                                    IRB Approval Date: 11/24/2020 
Version of protocol: 7 
IND number: 139015 
Institutional protocol number: OSU 17102 
11 
 
DLT definition 
 
Acute GVHD ≥ Grade 3 
 
Any non-hematologic toxicity ≥ Grade 3 related 
to Daratumumab 
 
Hematologic toxicity: grade 4 toxicity not related 
to the underlying disease and not responding to 
growth factor or transfusion within 7 days 
 
Grade 3 or higher non-neurologic immune-related 
adverse events (e.g. diarrhea, pruritus, rash) that 
responds to corticosteroids and improve to grade 1 
or less within 4 weeks will NOT count as DLTs. 
Optional biopsy of affected organs will be 
encouraged to help determine whether the 
immune-related condition is due to GVHD 
Enrollment schedule  
Dose level 1: Weekly Dara for eight doses; if no 
infusional toxicity observed or GVHD observed, proceed 
to next dose level. 3 patients at a time can be enrolled in 
one dose level.  
If no GVHD is observed after at least 2 weeks after DLI, 
enrollment will proceed to next dose level. 
Definitions for safety-evaluability  
Received at least one dose of Daratumumab  
Definition for DLT evaluability 
All patients are evaluable for DLT except patients who are 
unable to receive 3 doses of daratumumab in dose level 1, 
or 3 doses of daratumumab and DLT for dose levels 2 and 
3 due to progression of AML.  
DLT observation period will be from the first dose of 
daratumumab till 7 days post 3rd dose of daratumumab 
(for dose level 1) and from the first dose of daratumumab 
till at least 4 weeks post DLI (for dose level 2 and 3) 
Definitions for efficacy evaluability:  
 
All eligible patients who receive at least one dose of 
Daratumumab, do not withdraw consent, and are 
evaluated for response at week 8. 
Dose-limiting toxicity: 
Grade 3 or 4 GVHD 
Special situations 
1. If patients attain response before DLI, there will 
be three options at the discretion of treating 
physician : 
a. Proceed with DLI  

Date of protocol: 10/14/2020                                                    IRB Approval Date: 11/24/2020 
Version of protocol: 7 
IND number: 139015 
Institutional protocol number: OSU 17102 
12 
 
b. Continue Daratumumab maintenance( If 
Daratumumab is given as maintenance, a 
schedule of 16mg/kg every 2 weeks for 16 (8 
doses) weeks and then monthly for 6 months 
will be administered)  
c. Proceed with second transplant.  
2. If patients develop steroid-responsive GVHD and 
remission before DLI, there will be two options at 
the discretion of treating physician : 
a. Continue Daratumumab maintenance (If 
Daratumumab is given as maintenance, a 
schedule of 16mg/kg every 2 weeks for 16 
weeks (8 doses) and then monthly for 6 
months will be administered) 
b. Proceed with second transplant.  
 
 
 

Date of protocol: 10/14/2020                                                    IRB Approval Date: 11/24/2020 
Version of protocol: 7 
IND number: 139015 
Institutional protocol number: OSU 17102 
13 
 
3 KEY ROLES 
Principal Investigator Dr. Sumithira Vasu MBBS 
Statistician: Qiuhong Zhao MS.  
4 INTRODUCTION 
4.1 AML RELAPSE POST-TRANSPLANT  
Acute myeloid leukemia (AML) is a molecularly heterogeneous disease with significant genetic 
complexity1. Allogeneic hematopoietic cell transplantation (Allo-HCT) has curative potential and most 
patients with intermediate or adverse risk molecular and cytogenetic subtypes will proceed to allogeneic 
HCT in first complete remission2. With increasing availability of donor sources and reduced-intensity 
conditioning, number of transplants is expected to increase. However, AML relapse incidence post Allo-
HCT varies between 18-47% based on the conditioning regimen3,4.  Relapse after Allo-HCT has a dismal 
prognosis, with a median post-relapse overall survival (OS) of 3-6 months5,6. According to historical 
cohorts, if not transplanted for a second time, such patients have a 6-month median OS of only about 
10%. For example, chemotherapy and donor lymphocyte infusion provided discouraging post-relapse 
median OS of 51 and 84 days, respectively in a large recent study5. Although second Allo-HSCT may 
offer durable remissions7 , only a small number of patients after relapse are eligible to receive a second 
transplant. In a recent CIBMTR analysis of 1788 patients relapsing after allogeneic HSCT, 3-year overall 
survival was 4% for patients relapsing within 1-6 months after an allograft and 12% for patients who 
relapsed in the 6-24 months after an allograft8. Currently, there is no standard or satisfactory treatment 
available for this group of patients. We propose here a Phase I/II study to determine the activity and 
safety of Daratumumab in patients post Allo-HCT with relapsed AML and myelodysplastic syndrome 
(MDS) transformed to AML.  
4.2 ROLE OF DLI 
Recent studies have shown T-cell exhaustion in post-transplant relapses and that it can be reversed during 
effective human antileukemic responses to donor lymphocyte infusion (DLI)9. There is increasing 
evidence that T cell infiltration at site of malignancy is critical to disease control. In a group of chronic 
myeloid leukemia patients who traditionally have the highest responses to DLI( about 85%), Bachireddy 
et al found that baseline T cell content in marrow and subsequent increase in T cell content following DLI 
were higher in responders versus non-responders. Recent guidelines note recommended doses of DLI for 
related and unrelated donors10. In the halo setting with post-transplant cyclophosphamide11, Donor 
lymphocyte infusion with doses up to 1x10e6/kg were noted to have remission rates of up to 30% in 
patients with AML.  
4.3 PRECLINICAL DATA REGARDING DARATUMUMAB 
Daratumumab is a first-in-class anti-CD38 monoclonal antibody approved for treatment of refractory 
multiple myeloma; encouraging responses with an acceptable safety profile were seen in heavily pre-
treated patients12,13. Daratumumab has been shown to also have immunomodulatory effects on T cell 
subsets; increased T cell numbers (CD8+ cells) in both peripheral blood and bone marrow were observed 
following Daratumumab treatment. Responders had higher numbers of CD8+ t cells than non-responders, 
which was most pronounced after Cycle 3. A highly immunosuppressive subset of T-regs expressing 
CD38 decreased significantly following Daratumumab treatment14.  

Date of protocol: 10/14/2020                                                    IRB Approval Date: 11/24/2020 
Version of protocol: 7 
IND number: 139015 
Institutional protocol number: OSU 17102 
14 
 
In addition to the T cell effects, we have discovered that CD38 antibody-binding to AML cells can 
encourage cell-to-cell killing or fratricide. This is consistent with the fact that AML cells (both primary 
and cell lines) express Fc gamma Receptors much like fully differentiated monocytes and macrophages, 
and are capable of antibody-mediated destruction of target cells albeit at a lower efficiency15. Below, we 
provide data attesting this hypothesis. 
Methods: Primary patient samples were obtained from apheresis when patients presented with high white 
blood cell counts and required leukapheresis. AML cell lines MOLM-13, THP-1, OCI-AML3 and MV4-
11 were also used. Commercial anti-CD38 antibodies were used for these experiments.  
Results:  
I. 
IFN-γ promotes an activated M1 phenotype in AML cells. Myeloid cells within the context of 
tumors commonly display M2-like characteristics, which serves to promote tumor growth and 
survival. Here, we tested whether treatment with IFN-γ could skew AML cells toward an M1 
phenotype. We treated the AML cell lines MOLM-13, MV4-11, OCI-AML3 and THP-1 overnight 
with or without IFN-γ and measured expression of the M1 markers CD80 and CD86. Results showed 
that overnight treatment with IFN-γ significantly increased the expression in all 4 cell lines of both 
CD80 and CD86 (data not shown). We also verified increased surface expression of CD86 via flow 
cytometry (data not shown). Next, we treated samples from AML patients overnight with versus 
without IFN-γ and measured the expression of these markers. Results showed that transcripts for both 
CD80 (Figure 1) and CD86 (data not shown) were significantly increased. 
 

Date of protocol: 10/14/2020                                                    IRB Approval Date: 11/24/2020 
Version of protocol: 7 
IND number: 139015 
Institutional protocol number: OSU 17102 
15 
 
II. 
IFN-γ increases FcγRI expression and phagocytic ability in AML cells. It has previously been 
shown that IFN-γ could increase the expression of FcγR1 in AML cells which led to the investigation 
of IFN-γ treatment combined with drug-conjugated anti-FcγRI antibody as a potential therapy for 
AML. Here, we explored the possibility that IFN-γ treatment would not only increase FcγRI but 
would also enhance the phagocytic ability of these AML cells, as FcγRI is a major effector of 
phagocytosis in myeloid cells. For this, we first treated the AML cell lines MOLM-13, MV4-11, 
OCI-AML3 and THP-1 overnight with or without IFN-γ and measured FcγRI expression by qPCR 
and flow cytometry. Results showed that, as expected, IFN-γ significantly increased both the 
transcript (Figure 2A) and surface expression (Figure 2B) of FcγRI. Next, we treated the cell lines 
overnight as above, and then subjected them to a phagocytosis assay using antibody-opsonized sheep 
red blood cells as targets. As shown in Figure 2C, IFN-γ treatment significantly enhanced the 
phagocytic ability of MOLM-13 and THP-1, with MV4-11 and OCI-AML3 showing a trend toward 
enhancement. We then tested the effects of IFN-γ on patient samples and found that it significantly 
increased FcγRI expression (Figure 2D). These results indicate that IFN-γ can enhance not only the 
expression, but also the function, of FcγR in AML cells.  
 
III. 
IFN-γ increases CD38 expression in AML cells. Internalization of therapeutic antibodies by the 
tumor cells is beneficial within the context of antibody-drug conjugates, but such internalization also 
reduces the ability of immune effector cells to bind and destroy the targets. CD38 is currently being 
investigated as an antigen that shows less internalization than CD33, thereby potentially serving as a 
superior target for effector cell-mediated ADCC.  Hence, we measured the expression of CD38 on 
these cells. To do this we treated the AML cell lines MOLM-13, MV4-11, OCI-AML3 and THP-1 
overnight with or without IFN-γ and then measured levels of CD38. Results showed that IFN-γ 
treatment led to a significant increase in CD38 in all cell lines tested, as measured by qPCR (Figure 
3A) and by flow cytometry (Figure 3B). We next tested AML patient samples in similar fashion and 
found that IFN-γ significantly increased CD38 expression in these cells as well (Figure 3C). Hence, 

Date of protocol: 10/14/2020                                                    IRB Approval Date: 11/24/2020 
Version of protocol: 7 
IND number: 139015 
Institutional protocol number: OSU 17102 
16 
 
not only does IFN-γ promote FcγR expression and function in AML cells, it also increases the 
expression of a candidate antigen target for antibody therapy. Next, to test which concentration of 
IFN-γ was required for this up-regulation of CD38, we treated AML patient apheresis samples 
overnight with 0-10 ng/ml IFN-γ and measured CD38 via qPCR. Results showed that as little as 0.5 
ng/ml was sufficient to elicit a significant increase in CD38. 
 
 
IV. 
IFN-γ-mediated CD38 up-regulation requires activation of Jak/Stat, p38 and NF-κB. In order to 
determine which downstream signaling pathways were required for the up-regulation of CD38 seen 
A 
B 
C 
* 
* 
* 
* 
p=0.0176 
D 
0
1
2
3
4
UT
IFNγ 
0.5
IFNγ 1 IFNγ 5 IFNγ 
10
RCN (hCD38)

Date of protocol: 10/14/2020                                                    IRB Approval Date: 11/24/2020 
Version of protocol: 7 
IND number: 139015 
Institutional protocol number: OSU 17102 
17 
 
with IFN-γ treatment, we pre-treated AML patient apheresis samples with inhibitors for Erk, PI3K, 
p38 MAPK, Jak/STAT and NF-κB. Results showed that IFN-γ-mediated up-regulation of CD38 was 
significantly stunted in cells treated with inhibitors for Jak/Stat, p38 and NF-κB (Figures 4A, B and 
C, respectively), but not with inhibitors of the PI3K and Erk pathways. 
 
V. 
IFN-γ enhances antibody-mediated fratricide in AML cells. Results have shown that IFN-γ of AML 
cells could promote their shift toward an M1 phenotype, could enhance the expression and function of 
FcγR, and could also increase the expression of an antigen target for antibody therapy. This led us to 
test whether IFN-γ treatment could promote an antibody-mediated killing of AML cells by one 
another, a phenomenon termed fratricide. To test this we first examined whether IFN-γ-treated and 
antibody-opsonized THP-1 cells could form conjugates between one another.  For this THP-1 cells 
were primed overnight with 10 ng/ml IFN-γ. Cells were then labeled with either PKH-67 (green) or 
Claret (red) dye (Sigma Aldrich). The green-labeled cells were then incubated on ice for 60 minutes 
with 10 μg/ml anti-CD38, washed and mixed at a 1:1 ratio (red: green). Following 3 hour incubation 
at 37 °C, cells were washed, fixed in 4% paraformaldehyde and analyzed by fluorescence microscopy 
using a red/green dual-filter objective (Figure 5A). The number of antibody-dependent conjugates 
(Green-Red and Green-Green) and non-specific conjugates (red-red) was scored in a blinded fashion 
(Figure 5B). The results demonstrate that indeed THP-1 cells attach to one another in an antibody-
dependent manner. 
 
VI. 
CD38 antibody-opsonized cells engage in fratricide. 
We treated the AML cell lines MOLM-13, MV4-11, OCI-AML3 and THP-1 overnight with or without 
IFN-γ, then incubated them for an additional 18 hours with anti-CD38 antibody and measured cell death 
via LDH assays. As shown in Figures 6A-D, IFN-γ significantly enhanced the antibody-mediated killing 
within each respective AML cell line. To test whether this was due to a toxic effect of anti-CD38, we 
incubated the AML cell lines on immobilized anti-CD38 for the same length of time and found that LDH 
release was not affected (data not shown). This suggests that the anti-CD38 antibody led to cell-against-
cell killing, which was triggered and enhanced by IFN-γ pre-treatment. 
 

Date of protocol: 10/14/2020                                                    IRB Approval Date: 11/24/2020 
Version of protocol: 7 
IND number: 139015 
Institutional protocol number: OSU 17102 
18 
 
 
 
4.4 RATIONALE FOR PROPOSED STUDY 
CD38 expression has been demonstrated on a small subset of leukemic stem cells which are thought to be 
the reservoir for leukemic relapse. Daratumumab is an FDA approved antibody targeting CD38 in 
multiple myeloma. AML is not an indication approved by the FDA for Daratumumab. Apart from CD38 
targeting, Daratumumab also has immunomodulatory effects increasing the recruitment of T cells into the 
marrow16. Preclinical studies from OSU have shown the efficacy of Daratumumab in AML when used in 
combination with IFN-gamma which has resulted in upregulation of CD38. IFN-γ promotes graft-versus-
leukemia effects without directly interacting with leukemia cells in mice after allogeneic hematopoietic 
cell transplantation17,18. IFN-gamma levels are elevated in post-transplant patients post-conditioning, 
infections, GVHD, and during hematopoietic regeneration. 
Donor lymphocyte infusion is associated with a 15-30% chance of inducing remission but can be 
associated with GVHD. CD38 has also been shown to be an early biomarker for development of GVHD.  
We hypothesize that (i) IFN-gamma levels will be higher in post-transplant patients than healthy 
donors and (ii) combination of Daratumumab and endogenous IFN-gamma will mediate 
antileukemic efficacy post-transplant (iii) the combination of Daratumumab and donor 
lymphocytes will provide potent effectors (T cells and NK cells), recruit effectors to marrow and 
mediate graft-versus-leukemia effect. 
* 
* 
* 
* 
A 
B 
C 
D 

Date of protocol: 10/14/2020                                                    IRB Approval Date: 11/24/2020 
Version of protocol: 7 
IND number: 139015 
Institutional protocol number: OSU 17102 
19 
 
5 STUDY OBJECTIVES 
5.1 PRIMARY OBJECTIVE 
Primary Objective for Phase I study: 
To determine the maximum tolerated dose (MTD) of Daratumumab and escalating doses of donor 
lymphocyte infusions (DLI) in post-HCT patients with relapsed AML and MDS transformed to AML.  
 
Primary Objective for Phase II study: 
To evaluate overall response rate to Daratumumab and DLI by week 8 in patients with post-HCT relapsed 
AML and MDS 
5.2 SECONDARY OBJECTIVES 
1. To assess overall response rates in MRD positive patients and in patients with overt 
morphological relapse  
2. To assess MRD conversion rates from MRD positive to MRD negative.  
3. To determine the post-relapse 6-month OS rates of patients with relapsed AML and MDS 
following Allo-HSCT who are treated with Daratumumab 
4.  To determine the rates of GVHD (both grades II-IV and III-IV) and autoimmune side effects of 
Daratumumab within 3 months of completion of study 
5.  To determine the post-relapse 6-month PFS rates of patients with relapsed AML and MDS 
following Allo-HSCT who are treated with Daratumumab 
5.3 EXPLORATORY OBJECTIVES 
1. To compare CD38 expression levels in myeloid blasts and IFN-γ levels in plasma, by flow 
cytometry and PCR, at the time of relapse before starting Daratumumab and at progression or 
relapse after Daratumumab To compare peripheral blood T cell number and subsets (CD3, CD4, 
CD8, CD38 expression on T-regs, CD4 and CD8), T regs, B-regulatory cells, NK cell numbers 
and bone marrow T cell subsets, by flow cytometry, at the time of relapse before starting 
Daratumumab, at the time of partial/complete response to Daratumumab, and at the time of 
progression or relapse after Daratumumab 
2. To evaluate whether Daratumumab has (i) Direct anti-leukemia effects by measuring the 
expression of the M1 markers CD80 and CD86 by flow cytometry and PCR (ii) Antibody-
dependent cellular cytotoxicity (ADCC) and Antibody-dependent cellular phagocytosis (ADCP) 
by using chromium based ADCC assays, and a phagocytosis assay using antibody-opsonized 
sheep red blood cells as targets and (iii) Immune modulation of autologous immune system (NK 
cells, T cells, T-regs, B-regs, and MDSCS) in AML  
3. To evaluate the effect of Daratumumab on exosome content and clearance along with other 
soluble factors in AML 
4. To evaluate serum IFN levels pre- Daratumumab, during and post-Daratumumab 
5. To evaluate whether fratricide occurs in patients treated with Daratumumab 
 
6 STUDY ENPOINTS 
6.1 PRIMARY ENDPOINT 
Phase I study: Safety and feasibility of combination of Daratumumab and donor lymphocyte infusion.  

Date of protocol: 10/14/2020                                                    IRB Approval Date: 11/24/2020 
Version of protocol: 7 
IND number: 139015 
Institutional protocol number: OSU 17102 
20 
 
Phase II study:  Overall response rate to Daratumumab and DLI in patients with post-HCT relapsed 
AML and MDS 
6.2 SECONDARY ENDPOINTS FOR PHASE II  
ORR in MRD positive patients and in patients with overt morphological relapse 
MRD conversion rates 
 
6 month post-relapse progression-free survival 
 
6 month post-relapse overall survival 
 
3 month GVHD rate 
6.3 EXPLORATORY ENPOINTS FOR PHASE I AND II 
Samples will be retained and/or stored for potential future use in the OSU – Leukemia Tissue 
Bank for up to 10 years after completion of study. Samples will be coded to protect subject 
identify and only the PI (Dr. Vasu) will have access to the samples. All correlative studies will be 
conducted only at Ohio State University.  
Bone marrow:  
1. Expression of CD38 on bone marrow: CD38 expression and other phenotypic markers on bone 
marrow is checked prior to transplant. Most patients are in remission prior to transplant. Patients 
who were initially treated at OSU will have banked leukemia samples at the time of diagnosis. 
Expression of CD38 on samples at diagnosis and prior to transplant will be evaluated by flow 
cytometry. 
2. Expression of CD38 in lymphocytes in bone marrow: Percentage of lymphocytes in bone marrow 
pre- and post-treatment with Daratumumab will be studied. In addition to percentage, expression 
of CD38 on lymphocytes will be evaluated by flow cytometry.  
3. Phenotypic studies to evaluate T cell exhaustion/function will be performed on bone marrow 
samples pre-and post-treatment with Daratumumab at the specified time points 
4. Phenotypic studies to evaluate activation status of NK-cells will be performed on bone marrow 
samples pre-and post-treatment with Daratumumab 
5. T-cell, NK cell, B-cell, and MDSC infiltration in bone marrow will be evaluated on bone marrow 
samples pre-and post-treatment with Daratumumab 
6. Exosomes from bone marrow will be examined at these serial times for both number and also 
content (protein, mRNA, and mIRs) 
7. Serial assessment of microenvironment with stromal cell cultures. 
8. Three tubes from bone marrow will be collected at each time point. 
Peripheral blood: 
1. Chimerism analysis: Using single-nucleotide polymorphisms, relative contributions from donor 
vs. recipient in sorted CD3+ and CD33+ cells will be measured and expressed as a percentage. 
2. Immune reconstitution: Dr. Gerard Lozanski has developed a panel called the Immunome to 
study reconstitution of T cells, NK cells and B cells post-transplant. Specific information 
regarding stages of activation of T cells is also available from this panel.  
3. Immune response post Daratumumab: The Immunome panel will be performed at the following 
time points: Day 90, 180 and 365 (+/- 7days). 

Date of protocol: 10/14/2020                                                    IRB Approval Date: 11/24/2020 
Version of protocol: 7 
IND number: 139015 
Institutional protocol number: OSU 17102 
21 
 
4. Phenotypic studies to evaluate T-cell exhaustion will be performed on bone marrow samples pre-
and post-treatment with Daratumumab 
5. Phenotypic studies to evaluate activation status of NK-cells will be performed on bone marrow 
samples pre-and post-treatment with Daratumumab 
6. Measurements of cytokines including but not limited to IFN- γ will be measured at relapse, pre 
and post Daratumumab treatment. 
7. Exosomes from bone marrow will be examined at these serial times for both number and also 
content (protein, mRNA, and mIRs). 
8. CD38, CD55, and CD59 expression in circulating blood cells will be evaluated 
9. Three tubes of blood will be collected at each time point for correlative studies. 
 
7 STUDY DESIGN 
7.1 OVERVIEW OF STUDY DESIGN 
This is a phase I/II study that evaluates combination of Daratumumab and escalating doses of donor 
lymphocyte infusions. Donor lymphocyte infusions will be given within 72 hrs. of daratumumab dose. 
The following dose levels are used.  
1. Phase I study with the following dose levels for related sibling donors: 
a. Dose level 1: Dara 16mg/kg 
b. Dose level 2: Dara 16mg/kg + DLI (1 infusion at any time between weeks 3-5) : 1x10e6 
CD3/kg 
c. Dose level 3: Dara 16mg/kg + DLI (1 infusion at any time between weeks 3-5): 1x10e7 
CD3/kg 
2. Phase I study with the following dose levels for unrelated donors: 
c. Dose level 1: Dara 16mg/kg  
d. Dose level 2: Dara 16mg/kg + DLI (1 infusion at any time between weeks 3-5): 1x10e5 
CD3/kg  
e. Dose level 3: Dara 16mg/kg + DLI (1 infusion at any time between weeks 3-5): 1x10e6 
CD3/kg 
3. Phase I study with the following dose levels for haploidentical donors: 
f. Dose level 1: Dara 16mg/kg  
g. Dose level 2: Dara 16mg/kg + DLI (1 infusion at any time between weeks 3-5): 1x10e4 
CD3/kg  
h. Dose level 3: Dara 16mg/kg + DLI (1 infusion at any time between weeks 3-5): 1x10e5 
CD3/kg 
Patients with MRD will not be enrolled until the DLT period for dose level 1 has been completed and it 
has been determined that the treatment schedule is safe. Patients must be positive for MRD disease as 

Date of protocol: 10/14/2020                                                    IRB Approval Date: 11/24/2020 
Version of protocol: 7 
IND number: 139015 
Institutional protocol number: OSU 17102 
22 
 
determined by the combined analyses of flow cytometry, genomic sequencing and cytogenetics. Patients 
who do not demonstrate evidence of MRD in all three methods will not be eligible for the trial. 
Bone marrow biopsies are done at the completion of 8 weeks. The maximal tolerated dose of DLI is 
chosen for expansion to the phase II portion of the study.  
If patients are found to be in CR at the end of 8 weeks and treating physician concludes that patient 
continues to benefit from treatment, patients may proceed to Daratumumab maintenance with  a schedule 
of 16mg/kg every 2 weeks for 16 weeks (8 doses) and then monthly for 6 months . 
For patients with rapidly progressive disease despite 4 doses of Daratumumab, they will come off trial.  
The dose level that is deemed safe will be chosen for the phase II portion of the study.  
 
 
 
7.2 NUMBER OF PATIENTS 
For phase I, we expect to enroll a minimum of 3 and a maximum of 18 patients for the related donor 
portion and 3-18 patients for the unrelated donor cohort. Accounting for 10% unevaluable for DLT, we 
expect 4-20 patients for each cohort in summary we expect 8-40 patients for phase I portion of the study. 
Enrollment can occur in parallel for both related and unrelated donor arms of the study. For Phase II, we 
will expect to enroll 25 patients. 

Date of protocol: 10/14/2020                                                    IRB Approval Date: 11/24/2020 
Version of protocol: 7 
IND number: 139015 
Institutional protocol number: OSU 17102 
23 
 
7.3 DURATION OF STUDY 
For phase I related donor arm, we expect the study duration between 10 months to 3.5 years including 
DLT observation period, while for the unrelated donor arm, it will take about 8 months to 2.5 years.  For 
phase II, the study duration will be around 2 years including following up period. 
8 STUDY POPULATION 
8.1 INCLUSION CRITERIA 
1. Age ≥ 18 years  
2. AML or MDS relapse following Allo-HSCT (Morphological relapse, or MRD positive by flow 
cytometry, cytogenetics, and molecular mutations)  
3. Patients who received a 10/10 HLA-matched allogeneic HCT either from sibling donors or 
unrelated donors or at least a 5/10 haploidentical transplant for Dose level 2 and 3 
4. Patients with R/R AML must not be candidates for available therapies known to be effective for 
treatment of their AML. 
5. For patients in Dose level 1 (Daratumumab only), relapsed refractory AML patients who have 
previously not received an allogeneic HCT are eligible.  
6. Engraftment must have occurred as defined by platelet (PLT) count > 20,000/µL and ANC ≥ 0.5 
7. ECOG performance status < 3 
8. Creatinine clearance > 40 ml/min (Calculated or measured)  
9.  Aspartate aminotransferase (AST) < 3 x upper limit of normal (ULN), alanine aminotransferase 
(ALT) < 3 x ULN, and total bilirubin < 1.5 x ULN 
10. Off calcineurin inhibitors for at least 2 weeks 
11. Prednisone dose ≤ 20 mg/day.  
12. Patients with proliferative disease can be cytoreduced with cytotoxic chemotherapy at 
investigator’s discretion, but there should be at least a 14 day window between start of 
cytoreductive therapy and start of Daratumumab 
13. Blast count ˂ 20 K/day (hydrea use is allowed) 
14. Patient willing to agree to study-related research marrows 
15. Female patients of childbearing potential who are sexually active must be willing to use an 
effective barrier method of birth control to avoid pregnancy during the study and for a minimum 
of 3 months after stopping study treatment 
16. Male patients with partners of childbearing potential who are sexually active must be willing to 
use an effective barrier method of birth control to avoid pregnancy during the study and for a 
minimum of 3 months after stopping study treatment 
 
8.2 EXCLUSION CRITERIA 
1. No demonstrable evidence of donor chimerism (˂ 55 donor CD3 or CD33 chimerism) 
2. Patients with a molecular mutation without chromosomal abnormalities or declining chimerisms 
(MRD status must be verified by surface marker and mutational analyses) 
3. Active graft-versus-host disease (GVHD) grades I-IV; prior acute GVHD could have occurred but 
resolved at time of initiation of Daratumumab  
4.  Extensive chronic GVHD requiring ongoing immunosuppression with calcineurin inhibitors or 
more than 20 mg of prednisone 
5. Patients with FLT3+ AML or blast crisis CML who have not yet received post-transplant TKI 
therapy 

Date of protocol: 10/14/2020                                                    IRB Approval Date: 11/24/2020 
Version of protocol: 7 
IND number: 139015 
Institutional protocol number: OSU 17102 
24 
 
6. Active CNS or testicular disease 
7. Subject is: 
7.2 seropositive for human immunodeficiency virus (HIV) 
7.3 seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen [HBsAg]). 
Subjects with resolved infection (ie, subjects who are HBsAg negative but positive for antibodies 
to hepatitis B core antigen [anti-HBc] and/or antibodies to hepatitis B surface antigen [anti-HBs]) 
must be screened using real-time polymerase chain reaction (PCR) measurement of hepatitis B 
virus (HBV) DNA levels. Those who are PCR positive will be excluded. EXCEPTION: Subjects 
with serologic findings suggestive of HBV vaccination (anti-HBs positivity as the only serologic 
marker) AND a known history of prior HBV vaccination, do not need to be tested for HBV DNA 
by PCR. 
8. seropositive for hepatitis C (except in the setting of a sustained virologic response [SVR], defined 
as aviremia at least 12 weeks after completion of antiviral therapy). 
9. Patients must not have chronic obstructive pulmonary disease with a forced expiratory volume in 
1 second (FEV1) < 50% of predicted normal.  FEV1 is required for patients suspected of having 
chronic obstructive pulmonary disease and are not eligible if FEV1 is < 50% of predicted normal. 
10. Patients must not have moderate or severe persistent asthma within the past 2 years and must not 
have currently uncontrolled asthma of any classification. 
11. Active autoimmune disease prior to transplant 
12. Female patients of childbearing potential who are sexually active and unwilling to use an effective 
barrier method of birth control to avoid pregnancy during the study and for a minimum of 3 
months after study treatment. 
13. Male patients with partners of childbearing potential who are sexually active and unwilling to use 
an effective barrier method of birth control to avoid pregnancy during the study and for a 
minimum of 3 months after study treatment 
14. Concurrent use of any other investigational drugs 
9 DARATUMUMAB ADMINISTRATION 
Daratumumab will be dosed at 16mg/kg following guidelines provided in package insert. For 
management of infusion-related toxicities, see 9.2. 
9.1 RECOMMENDED CONCOMITANT MEDICATIONS 
9.1.1 
Pre-infusion Medication 
Administer pre-infusion medications to reduce the risk of infusion reactions to all patients 1-3 hours prior 
to every infusion of Daratumumab per OSU guidelines 
 
9.1.2 
Post-infusion Medication 
Administer post-infusion medication to reduce the risk of delayed infusion reactions to all patients as 
follows according to OSU guidelines.  
In addition, for any patients with a history of chronic obstructive pulmonary disease, consider prescribing 
post-infusion medications such as short and long-acting bronchodilators, and inhaled corticosteroids. 
Following the first four infusions, if the patient experiences no major infusion reactions, these additional 
inhaled post-infusion medications may be discontinued. 

Date of protocol: 10/14/2020                                                    IRB Approval Date: 11/24/2020 
Version of protocol: 7 
IND number: 139015 
Institutional protocol number: OSU 17102 
25 
 
9.2 DARATUMUMAB INFUSION RELATED REACTIONS 
For infusion reactions of any grade/severity, immediately interrupt the DARATUMUMAB infusion and 
manage symptoms. Management of infusion reactions may further require reduction in the rate of 
infusion, or treatment discontinuation of DARATUMUMAB as outlined below.  
• Grade 1-2 (mild to moderate): Once reaction symptoms resolve, resume the infusion at no more than 
half the rate at which the reaction occurred. If the patient does not experience any further reaction 
symptoms, infusion rate escalation may resume at increments and intervals as clinically appropriate 
up to the maximum rate of 200 mL/hour. 
• Grade 3 (severe): Once reaction symptoms resolve, consider restarting the infusion at no more than 
half the rate at which the reaction occurred. If the patient does not experience additional symptoms, 
resume infusion rate escalation at increments and intervals as clinically appropriate. Repeat the 
procedure above in the event of recurrence of Grade 3 symptoms. Permanently discontinue 
DARATUMUMAB upon the third occurrence of a Grade 3 or greater infusion reaction. 
• Grade 4 (life threatening): Permanently discontinue Daratumumab treatment. 
9.3 DONOR LYMPHOCYTE INFUSION  
Donor lymphocytes are typically infused as outpatient according to institutional guidelines. To allow for 
scheduling ease, DLI will be infused within 72 hrs. after the daratumumab dose, anytime between week 
3-4. .  
9.4 CRITERIA TO BE MET BEFORE EACH DOSE OF DARATUMUMAB 
Patients need to be evaluated with documentation of the following before starting each dose of 
Daratumumab: 
1. Patient is hemodynamically stable without concern for active infection 
2. No evidence of active GVHD 
3. Prednisone dose is ≤ 20mg/day. 
9.5 POST-TRANSPLANT STANDARD OF CARE CONCOMITANT MEDS 
Patients are recommended to be on ursodiol (Actigall) for liver protection. Patients will also be on 
antifungal prophylaxis (posaconazole is preferred), antiviral prophylaxis (acyclovir or valacyclovir) and 
anti-PCP prophylaxis (dapsone, Bactrim).  
9.6 DEFINITIONS OF DOSE LIMITING TOXICITY 
Dose limiting toxicity would be development of Grade 3-4 GVHD. GVHD will be graded according to 
the Glucksberg criteria. 
Dose-limiting toxicity is defined as: 
 
Grade 3-4 Acute GVHD  
 
Any Grade 3-4 non-hematologic toxicity related to Daratumumab 
 
Hematologic toxicity: grade 4 toxicity not related to the underlying disease and not responding to 
growth factor or transfusion within 7 days 
 

Date of protocol: 10/14/2020                                                    IRB Approval Date: 11/24/2020 
Version of protocol: 7 
IND number: 139015 
Institutional protocol number: OSU 17102 
26 
 
Grade 3 or higher non-neurologic immune-related adverse events (e.g. diarrhea, pruritus, rash) that 
respond to corticosteroids and improve to grade 1 or less within 4 weeks will NOT count as DLTs. 
Optional biopsy of affected organs will be encouraged to help determine whether the immune-related 
condition is due to GVHD. Once a patient develops Grade 3-4 GVHD, further enrollment will be on hold 
until safety and monitoring committee assesses toxicity. 
For patients developing Grade 2 GVHD, further doses of Daratumumab will be held until GVHD is 
controlled. Patients have to meet above-listed criteria before they can resume Daratumumab.  
In the phase II expansion part of the study, if >2 patients develop ≥ Grade 3 GVHD, we will stop 
enrollment and reassess safety. 
10 MANAGEMENT OF CLINICAL EVENTS 
10.1 CYTOPENIAS 
Bone marrow biopsies will be done at time of consent, prior to DLI and at week 8. Additional Bone 
marrow biopsies can be done at any time at discretion of treating physician. If bone marrow shows 
persistent disease, cytopenias would be attributed to persistent leukemia.   
Transfusions will follow institutional guidelines which typically are to keep Hgb> 7gm/dL and platelet 
(PLT) count more than 10K/µl.  
10.2 GRAFT VERSUS HOST DISEASE 
Patients will be assessed for GVHD at every visit, for new diagnosis of suspected GVHD, biopsy will be 
done whenever feasible. Management of GVHD will follow guidelines listed in the Programmatic 
approach to management of GVHD followed at the James.  
10.3 OTHER CLINICAL EVENTS 
For any grade 3-4 non-hematologic event observed, treating physician will determine relatedness as 
follows:   
 Related to leukemia 
 Definitely 
 Probably 
 Possibly 
 Unlikely 
 Unrelated 
 Related to transplant 
 Definitely 
 Probably 
 Possibly 

Date of protocol: 10/14/2020                                                    IRB Approval Date: 11/24/2020 
Version of protocol: 7 
IND number: 139015 
Institutional protocol number: OSU 17102 
27 
 
 Unlikely 
 Unrelated 
 Related to Daratumumab – if Yes, fill one of the boxes below 
 Definitely 
 Probably 
 Possibly 
 Unlikely 
 Unrelated 
 Related to DLI  
 Definitely 
 Probably 
 Possibly 
 Unlikely 
 Unrelated 
 
Is event expected - Yes or No   
11 DESCRIPTION OF INVESTIGATIONAL AGENT  
11.1 STORAGE, HANDLING AND ACCOUNTABILITY 
Daratumumab is a colorless to pale yellow, preservative-free solution for intravenous infusion supplied 
as: 
NDC 57894-502-05 contains one 100 mg/5 mL single-dose vial  
NDC 57894-502-20 contains one 400 mg/20 mL single-dose vial  
 
Storage and Stability  
Store in a refrigerator at 2ºC to 8ºC (36ºF to 46ºF). Do not freeze or shake. Protect from light. This 
product contains no preservative. 
11.2 SAFTEY INFORMATION FOR DARATUMUMAB 
Daratumumab is a CD38-directed cytolytic antibody that is FDA approved for multiple myeloma. Safety 
information was obtained from the package insert 
(https://www.darzalexhcp.com/shared/product/darzalex/darzalex-prescribing-information.pdf and shown 
below:  
1. Infusion reactions: Interrupt Daratumumab infusion for infusion reactions of any severity. 
Permanently discontinue the infusion in case of life-threatening infusion reactions.  

Date of protocol: 10/14/2020                                                    IRB Approval Date: 11/24/2020 
Version of protocol: 7 
IND number: 139015 
Institutional protocol number: OSU 17102 
28 
 
2. 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 
Daratumumab 
3. Neutropenia: Monitor complete blood cell counts periodically during treatment. Monitor 
patients with neutropenia for signs of infection. Dose delay may be required to allow recovery 
of neutrophils. 
4. Thrombocytopenia: Monitor complete blood cell counts periodically during treatment. Dose 
delay may be required to allow recovery of platelets. 
The most frequently reported adverse reactions (incidence ≥20%) in clinical trials were: infusion 
reactions, neutropenia, thrombocytopenia, fatigue, nausea, diarrhea, muscle spasms, back pain, pyrexia, 
cough, dyspnea, peripheral edema, peripheral sensory neuropathy and upper respiratory tract infection 
Patients with AML or MDS transformed to AML have pre-existing thrombocytopenia and neutropenia; 
abnormalities in blood counts will be attributed to underlying disease.  
The effects of Daratumumab on the developing fetus/embryo is not known. Patients will be counselled to 
use effective contraception methods after transplant and specifically during the time period of study 
participation and study follow-up.   
12 STUDY CONDUCT 
12.1 STUDY PROCEDURES 
12.1.1 PHYSICAL EXAMINATION 
A focused physical exam pertaining to vitals and assessment for GVHD will be performed at time of 
enrollment and prior to each dose of Daratumumab.  
12.1.2 LABORATORY EVALUATION 
At screening: 
1. CBC, CMP, LDH, Type and cross with DAT, pregnancy test( if applicable)  
2. CD3, CD33 peripheral blood chimerisms 
Prior to Each dose of Daratumumab: 
1. CBC, CMP 
End-of-study visit 
1. CD3 CD33 peripheral blood chimerisms  
Long-term follow-up to 6 months will occur – at month 3 and at month 6. These visits will be done when 
patient is evaluated by their treating physician. 

Date of protocol: 10/14/2020                                                    IRB Approval Date: 11/24/2020 
Version of protocol: 7 
IND number: 139015 
Institutional protocol number: OSU 17102 
29 
 
12.1.3 STUDY RELATED PROCEDURES AND STUDY CALENDAR 
 
Screeninga 
Pre‐1st Dose 
Daratumumab 
Post‐1st Dose 
Daratumumab 
Week 2 
Week 3 
Week 4 
Week 5 
Week 6 
Week 7 
Week 8 
Long Term 
Follow‐up 
 
 
Day 1 
Day 3 or 4 
Day 8 
Day 15 
Day 22 
Day 29 
Day 36 
Day 43 
Day 50 
Day 57‐71 
Informed Consent 
X 
 
 
 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
 
 
Physical Exam & Vital Signs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Pregnancy Test (if applicable) 
X 
 
 
 
 
 
 
 
 
 
 
Medication Record 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Performance Status 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Blood Draw (Complete Blood Count) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Blood Draw (Complete Metabolic Panel) 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
GVHD Assessment 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Donor Lymphocyte Infusion (DLI) 
 
 
 
 
 
X 
 
 
 
 
 
Adverse Event Monitoring 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Bone Marrow Biopsy 
X 
 
 
 
 
(Pre‐
DLI) X 
 
 
 
 
X 
Research Bone Marrow samples (3 green 
tops of 6 ml each) 
X 
 
 
 
 
X 
 
 
 
 
X 
Research blood samples (2 green tops(6 
ml each) and one red top (6 ml)) 
X 
X 
X 
x 
X 
X 
x 
X 
X 
x 
 
 
a Screening window is 28 days. 
 
The bone marrow biopsy at week 4 can be done at week 3, but it has to be done before the DLI. So, if the DLI can be arranged at week 4, then the 
marrow will be done week 3. For patients deemed eligible to receive maintenance therapy, the following procedures will be performed. 
Daratumumab will be administered if PLT count is > 100K and ANC> 500. 
 
 

Date of protocol: 10/14/2020                                                    IRB Approval Date: 11/24/2020 
Version of protocol: 7 
IND number: 139015 
Institutional protocol number: OSU 17102 
30 
 
 
Start of Daratumumab Maintenance a 
Week b 
Week 
9 
Week 
11 
Week 
13 
Week 
15 
Week 
17 
Week 
19 
Week 
21 
Week 
23 
Week 
25 
Week 
29 
Week 
33 
Week 
37 
Week 
41 
Week 
45 
CBC 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Vital signs 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
GVHD assessment 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Performance status 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Adverse event monitoring 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
a) Daratumumab maintenance, a schedule of 16mg/kg every 2 weeks for 16 (8 doses) weeks and then monthly for 6 months will be  
given.  
b) Daratumumab can be given +/- 3 days but there has to be a week interval between doses.  
marrow during Daratumumab maintenance is at the discretion of the physician and will be considered standard of care. 

Date of protocol: 10/14/2020                                                    IRB Approval Date: 11/24/2020 
Version of protocol: 7 
IND number: 139015 
Institutional protocol number: OSU 17102 
31 
 
TIME AND EVENTS SCHEDULE OVERVIEW 
  
Screening 
Phase 
Treatment Phase  
Follow-up Phase 
Notes 
Within 28 days 
of daratumumab 
Day 1 of each cycle (28-day 
cycles) 
EOT within 
30 days of 
last dose 
Prior 
to PD 
After PD 
(every 6 
months) 
 
Laboratory Assessments 
Hepatitis B 
(HBV) serology 
X 
 
Local testing for hepatitis B surface 
antigen (HBsAg), hepatitis B 
surface antibody (Anti-HBs), and 
hepatitis B core antibody (Anti-
HBc).  
Refer to Section 12.1.3 
HBV DNA 
testing 
X 
Q12W during treatment, at the End of Treatment Visit, and Q12W for 
up to 6 months after the last dose of study treatment 
For subjects with serologic 
evidence of resolved HBV 
infection (i.e., positive Anti-HBs or 
positive Anti-HBc) at Screening, 
HBV DNA testing by PCR must be 
performed locally.  
Refer to Section 12.1.3.  

Date of protocol: 10/14/2020                                                    IRB Approval Date: 11/24/2020 
Version of protocol: 7 
IND number: 139015 
Institutional protocol number: OSU 17102 
32 
 
Concomitant therapy 
Management of Hepatitis B Virus Reactivation 
Primary antiviral prophylaxis is permitted as per local standard of care.  Per protocol, HBV DNA 
testing by PCR is mandatory for subjects at risk for HBV reactivation. 
For subjects who are diagnosed with HBV reactivation while on treatment, study treatment should 
be interrupted until the infection is adequately controlled. If the benefits outweigh the risks, study 
treatment may be resumed with concomitant antiviral prophylaxis as per local standard of care. 
Consult a liver disease specialist as clinically indicated.  
STUDY EVALUATIONS 
HBV Serology 
All subjects will be tested locally for hepatitis B surface antigen (HBsAg), hepatitis B surface antibody 
(Anti-HBs), and hepatitis B core antibody (Anti-HBc) at Screening.  Additionally, subjects ongoing in the 
Treatment Phase who are within 6 months of starting study treatment when Protocol Amendment v.3 is 
implemented will be required to have HBV serology performed locally upon signing the updated ICF. 
HBV serology is not required at Screening or for subjects ongoing in the Treatment Phase who are within 
6 months of starting study treatment if this was performed as part of standard of care within 3 months 
prior to first dose. 
HBV DNA Tests:  
Subjects who are positive for Anti-HBc or Anti-HBs will undergo testing for hepatitis B DNA by 
PCR. Subjects with serologic findings suggestive of HBV vaccination (Anti-HBs positivity as 
the only serologic marker) and a known history of prior HBV vaccination do not need to be 
tested for HBV DNA by PCR. During and following study treatment, subjects who have history 
of HBV infection will be closely monitored for clinical and laboratory signs of reactivation of 
HBV as specified in the Time and Events Schedule (Table 12.1.3).  Where required by local law, 
the results of HBV testing may be reported to the local health authorities. 
 
12.2 DISEASE ASSESSMENT TIMELINES 
Disease assessment will be performed at the following time points: 
Screening for trial  
Bone marrow biopsy pre-DLI 
End of study bone marrow biopsy  
In addition, bone marrow biopsies can be performed at the discretion of the primary physician.  

Date of protocol: 10/14/2020                                                    IRB Approval Date: 11/24/2020 
Version of protocol: 7 
IND number: 139015 
Institutional protocol number: OSU 17102 
33 
 
12.3 COMPLETION OF TREATMENT 
Treatment with study drug may be discontinued for any of the following reasons: 
 Adverse event. 
 Protocol violation. 
 Unsatisfactory therapeutic response. 
 Study terminated by sponsor. 
 Withdrawal by subject. 
 Lost to follow-up. 
              Other 
12.4 COMPLETION OF STUDY 
Patients will be considered to have completed the study  
1. If they withdrew from the study 
2. Come off study due to progressive disease 
3.Complete the 6 month follow up period after completion of treatment  
 
12.5 POST-TREATMENT FOLLOW-UP ASSESSMENTS 
Patients who remain in remission will be followed for development of acute and chronic GVHD and 
safety during clinic visits for at least 12 months after study treatment or until the patient’s death or 
withdrawal of consent or termination of the study by the sponsor. 
All patients will be followed for OS until death, withdrawal of consent, termination of study by the 
sponsor, or for a maximum of 1 year after until the last patient is enrolled in the study. Survivor 
information may be collected by methods that include, but are not limited to, telephone, e-mail, mail, or 
retrieved from online or other databases (e.g., social security indexes). 
12.6 EXPECTED TIMELINES FOR RECRUITMENT, DATA REPORTING 
First patient enrollment: February 2019? 
13 ADVERSE EVENT MONITORING AND REPORTING 
Adverse events of special interest are events that the COMPANY is actively monitoring as a result of a 
previously identified signal (even if non-serious). These adverse events are: 
 
Infusion reactions: ≥ grade 3  
 
Infections: ≥ grade 4   
 
Cytopenias: ≥ grade 4  
 
HBV Reactivation  
 
Other malignancies 
 

Date of protocol: 10/14/2020                                                    IRB Approval Date: 11/24/2020 
Version of protocol: 7 
IND number: 139015 
Institutional protocol number: OSU 17102 
34 
 
Any Adverse Event of Special Interest that is to be reported to the COMPANY should be recorded on a 
Serious Adverse Event Report Form and be reported to the COMPANY within 24 hours of knowledge 
of the event. 
 
13.1 Individual Case Safety Report (ICSR) 
A valid ICSR must contain the four minimum criteria required to meet regulatory reporting requirements. 
 
an identifiable subject (but not disclosing personal information such as the subject’s name, 
initials or address) 
 
an identifiable reporter (investigational site) 
 
a J&J medicinal product 
 
an adverse event, outcome, or certain special situations 
 
The minimum information required is: 
 
suspected J&J medicinal product (doses, indication) 
 
date of therapy (start and end date, if available) 
 
batch or lot number, if available 
 
subject details (subject ID and country) 
 
gender 
 
age at AE onset 
 
reporter ID 
 
adverse event detail (AE verbatim in English), onset date, relatedness, causality, action taken, 
outcome, (if available) 
 
J&J protocol ID 
 
13.2 Product Quality Complaint (PQC) 
A product quality compliant is defined as any suspicion of a product defect related to a potential quality 
issue during manufacturing, packaging, release testing, stability monitoring, dose preparation, storage or 
distribution of the product, or delivery system.  Not all PQCs involve a subject.  Lot and batch numbers 
are of high significance and need to be collected whenever available. 
Examples of PQC include but not limited to: 
 
Functional Problem: e.g., altered delivery rate in a controlled release product 
 
Physical Defect:  e.g. abnormal odor, broken or crushed tablets/capsules 
 
Potential Dosing Device Malfunction: e.g.,  auto injector button not working, needle 
detaching from syringe 
 
Suspected Contamination 
 
Suspected Counterfeit 
 
13.3 Serious Adverse Event (SAE) 
A serious adverse event based on ICH and EU Guidelines on Pharmacovigilance for Medicinal Products 
for Human Use is any untoward medical occurrence that at any dose: 

Date of protocol: 10/14/2020                                                    IRB Approval Date: 11/24/2020 
Version of protocol: 7 
IND number: 139015 
Institutional protocol number: OSU 17102 
35 
 
 
Results in death 
 
Is life-threatening 
(The subject was at risk of death at the time of the event. It does not refer to an event that 
hypothetically might have caused death if it were more severe.) 
 
Requires inpatient hospitalization or prolongation of existing hospitalization 
 
Results in persistent or significant disability/incapacity 
 
Is a congenital anomaly/birth defect 
 
Is a suspected transmission of any infectious agent via a medicinal product 
 
Is medically important* 
 
*Medical and scientific judgment should be exercised in deciding whether expedited reporting is 
also appropriate in other situations, such as important medical events that may not be 
immediately life threatening or result in death or hospitalization but may jeopardize the subject or 
may require intervention to prevent one of the other outcomes listed in the definition above. 
These should usually be considered serious. 
 
NOTE: DEATH FOR ANY REASON SHOULD BE REPORTED AS A SERIOUS ADVERSE 
EVENT. 
 
13.3.1 Hospitalization 
For reports of hospitalization, it is the sign, symptom or diagnosis which led to the hospitalization 
that is the serious event for which details must be provided. 
 
Any event requiring hospitalization or prolongation of hospitalization that occurs during the study 
must be reported as a serious adverse event, except hospitalizations for the following: 
 
Hospitalizations not intended to treat an acute illness or adverse event (e.g., social 
reasons such as pending placement in long-term care facility) 
 
Surgery or procedure planned before entry into the study. [Note: Hospitalizations that 
were planned before the start of data collection and where the underlying condition for 
which the hospitalization was planned has not worsened will not be considered serious 
adverse events. Any adverse event that results in a prolongation of the originally planned 
hospitalization is to be reported as a new serious adverse event.] 
 
[For convenience the investigator may choose to hospitalize the subject for the duration 
of the treatment period.]  
 
13.3.2 Life-Threatening Conditions 
Disease progression should not be recorded as an adverse event or serious adverse event term; 
instead, signs and symptoms of clinical sequelae resulting from disease progression/lack of 
efficacy will be reported if they fulfill the serious adverse event definition. 
 
1. Unlisted (Unexpected) Adverse Event/Reference Safety Information 

Date of protocol: 10/14/2020                                                    IRB Approval Date: 11/24/2020 
Version of protocol: 7 
IND number: 139015 
Institutional protocol number: OSU 17102 
36 
 
An adverse event is considered unlisted if the nature or severity is not consistent with the 
applicable product reference safety information. For a medicinal product(s) with a marketing 
authorization, the expectedness of an adverse event will be determined by whether or not it is 
listed in the applicable product information.  
 
http://www.darzalex.com/shared/product/darzalex/darzalex-prescribing-information.pdf 
 
For DARZALEX™ (daratumumab),the expectedness of an adverse event will be determined by 
whether or not it is listed in the Investigator's Brochure. 
 
2. Special Reporting Situations  
Safety events of interest for a J&J medicinal product that require expediting reporting and/or safety 
evaluation include, but are not limited to: 
 
Drug exposure during pregnancy (maternal and paternal) 
 
Overdose of a J&J medicinal product  
 
Exposure to a J&J medicinal product from breastfeeding  
 
Suspected abuse/misuse of a J&J medicinal product 
 
Inadvertent or accidental exposure to a J&J medicinal product  
 
Medication error (includes potential, intercepted or actual) involving a J&J product (with or 
without patient exposure to the J&J Product(s) Under Study, e.g., name confusion) 
 
Suspected transmission of any infectious agent via administration of a medicinal product 
 
 Unexpected therapeutic or clinical benefit from use of a J&J medicinal product 
 
Any failure of expected pharmacological action (i.e., lack of effect) of a J&J medicinal 
product 
 
 
These safety events may not meet the definition of an adverse event; however, from a 
COMPANY perspective, they are treated in the same manner as adverse events. Special situations 
should be recorded on the Adverse Event page of the CRF. 
 
Any special situation that meets the criteria of a serious adverse event should be recorded on a 
Serious Adverse Event Report Form and be reported to the COMPANY within 24 hours of 
becoming aware of the event. 
 
13.4 PREGNANCY 
All initial reports of pregnancy must be reported to COMPANY by the PRINCIPAL INVESTIGATOR 
within 24 hours of becoming aware of the event using the Serious Adverse Event Form. Abnormal 
pregnancy outcomes (e.g. spontaneous abortion, fetal death, stillbirth, congenital anomaly, ectopic 
pregnancy) are considered serious adverse events and must be reported using the Serious Adverse Event 
Form.  
Any subject who becomes pregnant during the study must be promptly withdrawn from the study and 
discontinue further study treatment. 

Date of protocol: 10/14/2020                                                    IRB Approval Date: 11/24/2020 
Version of protocol: 7 
IND number: 139015 
Institutional protocol number: OSU 17102 
37 
 
Because the effect of the J&J medicinal product on sperm is unknown, pregnancies in partners of male 
subjects exposed to a J&J medicinal product will be reported by the PRINCIPAL INVESTIGATOR 
within 24 hours of their knowledge of the event using the Serious Adverse Event Form.  Depending on 
local legislation this may require prior consent of the partner. 
Follow-up information regarding the outcome of the pregnancy and any postnatal sequelae in the infant 
will be required. 
13.5 Maintenance of Safety Information 
All safety data should be maintained in a clinical database in a retrievable format. The Ohio State 
University and PRINCIPAL INVESTIGATOR shall provide all adverse events, both serious and non-
serious, in report format. However, in certain circumstances more frequent provision of safety data may 
be necessary, e.g. to fulfill a regulatory request, and as such the data shall be made available within a 
reasonable timeframe at COMPANY’s request. 
 
13.6 Procedures for Reporting Safety Data and Product Quality Complaints (PQCs) for 
J&J medicinal products to the COMPANY 
All adverse events and special situations, whether serious or non-serious, related or not related, following 
exposure to a J&J medicinal product are to be documented by the investigator and recorded in the CRF 
and in the subject’s source records. Investigators must record in the CRF their opinion concerning the 
relationship of the adverse event to a J&J medicinal product.  
All (serious and non-serious) adverse events reported for a J&J medicinal product should be followed-up 
in accordance with clinical practice. 
13.6.1 SAEs and Special Reporting Situations 
All serious adverse events that have not resolved by the end of the study, or that have not 
resolved upon discontinuation of the subject's participation in the study, must be followed until 
any of the following occurs: 
 
The event resolves 
 
The event stabilizes 
 
The event returns to baseline, if a baseline value/status is available 
 
The event can be attributed to agents other than the study drug or to factors unrelated to study 
conduct 
 
It becomes unlikely that any additional information can be obtained (subject or health care practitioner 
refusal to provide additional information, lost to follow-up after demonstration of due diligence with 
follow-up efforts) 
The Ohio State University and the PRINCIPAL INVESTIGATOR will transmit all SAEs and 
special situations following exposure to a J&J product under study in a form provided by the 
COMPANY in accordance with Section 10, Transmission Methods, in English within 24-hours 
of becoming aware of the event(s). 
 

Date of protocol: 10/14/2020                                                    IRB Approval Date: 11/24/2020 
Version of protocol: 7 
IND number: 139015 
Institutional protocol number: OSU 17102 
38 
 
All follow-up information for serious adverse events that are not resolved at the end of the study 
or by the time of patient withdrawal must be reported directly by the PRINCIPAL 
INVESTIGATOR, within 24 hours becoming aware, to COMPANY using COMPANY’s 
Serious Adverse Event Report  
All available clinical information relevant to the evaluation of a related SAE, serious ADR or 
special situation is required. 
 
 
The Ohio State University and/or PRINCIPAL INVESTIGATOR is responsible for ensuring 
that these cases are complete and if not are promptly followed-up. A safety report is not 
considered complete until all clinical details needed to interpret the case are received. 
Reporting of follow-up information should follow the same timeline as initial reports. 
 
Copies of any and all relevant extraordinary (not including routine initial or follow-up ICSR 
submission) correspondences with regulatory authorities and ethics committees regarding any 
and all serious adverse events, irrespective of association with the J&J Product under study, 
are to be provided COMPANY using a transmission method in Section 8within 24 hours of 
such report or correspondence being sent to applicable health authorities. 
 
13.6.2 Non-Serious AEs 
All non-serious adverse events should be reported to COMPANY according to the timeframe 
outlined in the Research Funding Agreement section entitled Reporting of Data. 
13.6.3 PQC Reporting 
A PQC may have an impact on the safety and efficacy of the product. Timely, accurate, and 
complete reporting and analysis of PQC information from studies are crucial for the protection of 
patients, investigators, and COMPNAY, and are mandated by regulatory agencies worldwide. 
COMPANY has established procedures in conformity with regulatory requirements worldwide to 
ensure appropriate reporting of PQC information. Lot and/or Batch #s shall be collected or any 
reports failure of expected pharmacological action (i.e., lack of effect). The product should be 
quarantined immediately and if possible, take a picture. 
 
All initial PQCs involving a J&J medicinal product under study must be reported to COMPANY 
by the PRINCIPAL INVESTIGATOR within 24 hours after being made aware of the event. 
The COMPANY contact will provide additional information/form to be completed. 
 
If the defect for a J&J medicinal product under study is combined with either a serious adverse 
event or non-serious adverse event, the PRINCIPAL INVESTIGATOR must report the PQC to 
the COMPANY according to the serious adverse event reporting timelines.  A sample of the 
suspected product should be maintained for further investigation if requested by the COMPANY. 
 
3. Reporting Procedures for Reporting Safety Data and Product Quality Complaints (PQCs) for 
Non-J&J Medicinal Products  
For SAEs, special reporting situations and PQCs following exposure to a non-J&J medicinal product 
under study, the PRINCIPAL INVESTIGATOR should notify the appropriate regulatory/competent 
authority or the manufacturer of that medicinal product (in the absence of appropriate local 
legislation) as soon as possible. 

Date of protocol: 10/14/2020                                                    IRB Approval Date: 11/24/2020 
Version of protocol: 7 
IND number: 139015 
Institutional protocol number: OSU 17102 
39 
 
4. Transmission Methods 
The following methods are acceptable for transmission of safety information to the COMPANY: 
 
Electronically via J&J SECURE Email service (preferred) , to IIS-BIO-VIRO-GCO@its.jnj.com 
 
 For business continuity purposes, if SECURE Email is non-functional: 
o Facsimile (fax), receipt of which is evidenced in a successful fax transmission report, to  
1-866-451-0371 
 
Telephone (if fax is non-functional) 
 
Every adverse event will follow the same reporting Guidelines: For any grade 3-4 non-hematologic event 
observed, treating physician will determine relatedness as follows:   
 Related to leukemia 
 Definitely 
 Probably 
 Possibly 
 Unlikely 
 Unrelated 
 Related to transplant 
 Definitely 
 Probably 
 Possibly 
 Unlikely 
 Unrelated 
 Related to Daratumumab – if Yes, fill one of the boxes below 
 Definitely 
 Probably 
 Possibly 
 Unlikely 
 Unrelated 
 Related to DLI  
 Definitely 
 Probably 

Date of protocol: 10/14/2020                                                    IRB Approval Date: 11/24/2020 
Version of protocol: 7 
IND number: 139015 
Institutional protocol number: OSU 17102 
40 
 
 Possibly 
 Unlikely 
 Unrelated 
Is event expected - Yes or No   
 
 
14 STUDY-SPECIFIC COMMITTEES  
14.1 DOSE ESCALATION AND ADVERSE EVENT MONITORING CALLS  
Once a patient is enrolled, safety and monitoring calls will occur weekly. If GVHD is identified, 
relatedness and attribution will be discussed by Investigator and monitoring committee will decide on 
further enrollment.  
15 DATA HANDLING AND RECORD-KEEPING 
15.1 ECRFs 
Case report forms are presented in the appendix.  
16 STATISTICAL CONSIDERATIONS 
Study design/Sample size 
This is a phase I/II study evaluating the combination of Daratumumab and escalating doses of DLI in 
patients with relapsed AML or transformed from MDS to AML post allo-HCT. Three dose levels will be 
used for related sibling donors and unrelated donors respectively. 
 
Study Design: The standard 3+3 design will be applied to determine MTD of donor lymphocyte infusion 
when given with a fixed dose of Daratumumab. The dose escalation process for related sibling donor and 
unrelated donor will be conducted concurrently, but separately.  
Dose escalation will proceed within each cohort according to the following scheme.  
Number of Subjects with DLT at a 
Given Dose Level 
Escalation Decision Rule 
0 out of 3 
Enter 3 subjects at the next dose level. 
1 out of 3 
Enter 3 more subjects at this dose level. 
 
If 0 of these 3 subjects experience DLT, proceed to the next dose 
level. 
 
If 1 or more of this group suffer DLT, then dose escalation is stopped, 
and this dose is declared the maximally administered dose. Three (3) 

Date of protocol: 10/14/2020                                                    IRB Approval Date: 11/24/2020 
Version of protocol: 7 
IND number: 139015 
Institutional protocol number: OSU 17102 
41 
 
additional subjects will be entered at the next lowest dose level if 
only 3 subjects were treated previously at that dose. 
>2 
Dose escalation will be stopped. This dose level will be declared the 
maximally administered dose (highest dose administered). Three (3) 
additional subjects will be entered at the next lowest dose level if only 3 
subjects were treated previously at that dose. 
<1 out of 6 at highest dose level 
below the maximally administered 
dose 
This is generally the recommended maximally tolerated dose.  
 
The MTD will be defined as the highest safely tolerated dose where at most one patient in six experiences 
DLT during DLT observation period. The DLT observation period is defined as below.  
Dose Level  
DLT observation period 
1 
From the first dose of Daratumumab till 7 days post 3rd dose 
2/3 
From the first dose of Daratumumab till at least 4 weeks post 
DLI 
 
If a patient in dose level 1 receives less than 3 doses of Daratumumab due to reasons other than toxicity, 
then this patient will not be evaluable for DLT and will be replaced. An additional patient will be added to 
the dose cohort. For dose level 2 or 3, if a patient does not receive 3 doses of Daratumumab and DLI due 
to reasons other than toxicity, then this patient will not be evaluable and will be replaced. There will be no 
intrapatient dose escalation. Phase I may involve as few as 3 patients (three at the starting dose level if ≥ 2 
DLTs are experienced) and a maximum of 18 patients will be treated, six at each of the 3 dose levels. We 
assume that 10% of the patients in this group will not be evaluable due to not finishing the DLT 
observation period. So we expect to accrue a minimum of 4 patients and a maximum of 20 patients. 
At OSU, 125 patients with AML/MDS underwent allo-HSCT in 2012 and 2013. Among these, 32 
patients relapsed. About 40% were from related donor and 60% from unrelated donor. So we expect to 
accrue approximately 6 patients for the related sibling donor cohort and 10 patients for the unrelated 
donor cohort per year. Hence, the minimum study duration for phase I would be about 8-10 months and 
the maximum study duration would be around 2.5-3.5 years (accounting for the DLT observation period) 
for related sibling donors and unrelated donors respectively.  
After the MTD has been established, we will expand to Phase II trial.  For phase II part, considering that 
patients receiving transplant from related sibling donor or unrelated donor with each treated at the 
corresponding MTD of Daratumumab plus DLI are expected to have similar profiles for response and 
toxicities, we will combine these 2 cohorts together in phase II stage. The null hypothesis is that 
combination of Daratumumab and DLI has a response rate of < 10% in patients with relapsed AML 
following allo-HSCT. The alternative hypothesis is that Daratumumab has a response rate of at least 30% 
in patients with relapsed AML following allo-HSCT. With a type 1 error (alpha): 0.05, and a type 2 error 
(beta = 1 – power): 0.20, the sample size would be 25 patients for Phase II. If the number of patients 
achieving ORR is 6 or more, then we reject the null hypothesis. We would include 3-6 patients from 

Date of protocol: 10/14/2020                                                    IRB Approval Date: 11/24/2020 
Version of protocol: 7 
IND number: 139015 
Institutional protocol number: OSU 17102 
42 
 
phase I who are treated at MTD in phase II analysis. Assuming 10% of the patients would be not 
evaluable for efficacy, we would expect to enroll 25 patients in phase II. With approximately 16 patients 
per year, and the study duration for phase II would be around 2 years including the follow up period (6-
months). 
16.1 Study endpoints: 
Primary endpoint for phase I: 
MTD of combination of Daratumumab and donor lymphocyte infusion  
 
Primary endpoint for phase II: 
Overall response rate to Daratumumab and DLI in patients with post-HCT relapsed AML and MDS 
 
Secondary endpoints for phase II: 
 ORR in MRD positive patients and in patients with overt morphological relapse 
 MRD conversion rates 
 6 month post-relapse progression-free survival 
 6 month post-relapse overall survival 
 3 month GVHD rate 
16.2 Analysis methods: 
Analysis datasets: 
Efficacy sets: All evaluable patients will be included in the analysis of the primary endpoint. The 
term evaluable is defined as any eligible patient who receives at least one dose of Daratumumab, 
does not withdraw consent, and is evaluated for response week 8; patients who fail to have a week-8 
assessment due to early progression, death or toxicity will also be considered evaluable for response 
and categorized as non-responders. Patients who fail to have a week-8 assessment for other reasons 
(e.g., refusal due to travel constraints) will be considered unevaluable and will not be included in the 
denominator when calculating ORR rate.  
Safety sets: The safety analysis dataset will include all eligible patients who receive one dose of 
daratumumab.  
The adverse events will be examined and worst grade adverse events will be recorded for each 
patient and summarized by type, severity, and attribution (if possible) using NCI CTCAE version 4 
criteria.  Tolerability of the regimen will be assessed by summarizing the number of patients who 
require dose modifications and/or dose delays. In addition, we will also capture the proportion of 
patients who go off treatment due to adverse events or even those who refuse further treatment for 
lesser toxicities that inhibit their willingness to continue participation on the trial. All patients who 
have received at least one dose of daratumumab will be evaluable for toxicity and tolerability.  
The primary endpoint of phase II is to evaluate overall response rates (ORR) to the combination of 
Daratumumab and DLI. The ORR will be defined as complete remission (CR), complete remission 
with incomplete marrow recovery (CRi), partial remission (PR) and morphological leukemia free 

Date of protocol: 10/14/2020                                                    IRB Approval Date: 11/24/2020 
Version of protocol: 7 
IND number: 139015 
Institutional protocol number: OSU 17102 
43 
 
state (MLFS). The proportion of patients achieving ORR among efficacy sets will be calculated and 
95% confidence interval will be estimated. In addition, the ORR among patients who received at 
least 3 doses of Daratumumab and DLI will be calculated as well. The ORR rate among MRD 
positive patients and patients with overt morphological relapse will be estimated as well. The MRD 
conversion rate from MRD positive to MRD negative, and the 3-month GVHD rate (both grade II-
IV and III-IV) will be similarly analyzed. 
Demographical and clinical characteristics of study patients will be described using mean and 
standard deviation, median and range, or frequency and percent depending on the data type and 
distribution. Overall survival (OS) will be defined as the time from the first treatment of 
Daratumumab to death or last contact date if no death.  Progression free survival (PFS) will be 
defined as the time from the first treatment of Daratumumab to the date of progression or death or 
last clinical assessment date if no progression or death. Kaplan-Meier curves will be generated to 
estimate OS/PFS at 6 months. The association between patient characteristics and OS/PFS will be 
evaluated in univariable Cox proportional hazard regression model. 
To examine the rate of GVHD (both grade II-IV and III-IV), the event will be onset of GVHD and 
time to GVHD will be defined as the period of time from first treatment of Daratumumab to the 
onset of GVHD. Death and early relapse without GVHD will be competing risks. Cumulative 
incidence rate of GVHD at 3-month with 95% confidence intervals will be estimated from the 
cumulative incidence curves. Competing risk regression analysis will be conducted to estimate the 
association between patient characteristics and GVHD.  
For pre/post-treatment comparisons in the correlative part of the study, a paired t-test will be applied. 
Two-tailed p values <0.05 will be considered statistically significant in all analyses.   
16.3 SAFETY ANALYSIS 
The investigator-study team will collectively discuss study conduct and accumulating safety and other 
data through teleconferences. In Phase 1, it is expected that these discussions will be scheduled to occur 
immediately following DLT window for the third patient of each cohort unless accrual to the study and 
the need for decisions regarding dose escalation or stage progression indicate the need for more frequent 
reviews. In Phase 2, it is expected that these discussions will occur every month to discuss study conduct 
and accumulating safety and efficacy data through teleconferences.  
A status report about adverse events, accrual will be submitted every 6 months to the Data Safety 
monitoring committee at Ohio State University  
Patients who have evidence of rapidly progressive disease after 4 doses of Daratumumab will come off 
trial.  
17 QUALITY CONTROL AND QUALITY ASSURANCE 
Protocol Deviations 
The investigator should not deviate from the protocol, except where necessary to eliminate an immediate 
hazard to study subjects. Should other unexpected circumstances arise that will require deviation from 
protocol-specified procedures, the investigator should consult with the sponsor or designee (and IRB or 
IEC, as required) to determine the appropriate course of action. There will be no exemptions (a 

Date of protocol: 10/14/2020                                                    IRB Approval Date: 11/24/2020 
Version of protocol: 7 
IND number: 139015 
Institutional protocol number: OSU 17102 
44 
 
prospectively approved deviation) from the inclusion or exclusion criteria. The site should document all 
protocol deviations in the subject’s source documents. In the event of a significant deviation, the site 
should notify the IRB. Significant deviations include, but are not limited to, those that involve fraud or 
misconduct, increase the health risk to the subject, or confound interpretation of primary study 
assessment. A Protocol Deviation Form should be completed by the sponsor or designee for any 
significant deviation from the protocol. 
 
 
 
 

Date of protocol: 10/14/2020                                                    IRB Approval Date: 11/24/2020 
Version of protocol: 7 
IND number: 139015 
Institutional protocol number: OSU 17102 
45 
 
 
18 References 
 
1. 
Patel JP, Gonen M, Figueroa ME, et al. Prognostic relevance of integrated genetic profiling in 
acute myeloid leukemia. The New England journal of medicine. Mar 22 2012;366(12):1079-1089. 
2. 
Cornelissen JJ, Blaise D. Hematopoietic stem cell transplantation for patients with AML in first 
complete remission. Blood. Jan 7 2016;127(1):62-70. 
3. 
Pasquini MC, Devine S, Mendizabal A, et al. Comparative outcomes of donor graft CD34+ 
selection and immune suppressive therapy as graft-versus-host disease prophylaxis for patients 
with acute myeloid leukemia in complete remission undergoing HLA-matched sibling allogeneic 
hematopoietic cell transplantation. Journal of clinical oncology : official journal of the American 
Society of Clinical Oncology. Sep 10 2012;30(26):3194-3201. 
4. 
Devine SM, Owzar K, Blum W, et al. Phase II Study of Allogeneic Transplantation for Older 
Patients With Acute Myeloid Leukemia in First Complete Remission Using a Reduced-Intensity 
Conditioning Regimen: Results From Cancer and Leukemia Group B 100103 (Alliance for 
Clinical Trials in Oncology)/Blood and Marrow Transplant Clinical Trial Network 0502. Journal 
of clinical oncology : official journal of the American Society of Clinical Oncology. Dec 10 
2015;33(35):4167-4175. 
5. 
Arellano ML, Langston A, Winton E, Flowers CR, Waller EK. Treatment of relapsed acute 
leukemia after allogeneic transplantation: a single center experience. Biology of blood and 
marrow transplantation : journal of the American Society for Blood and Marrow 
Transplantation. Jan 2007;13(1):116-123. 
6. 
Pollyea DA, Artz AS, Stock W, et al. Outcomes of patients with AML and MDS who relapse or 
progress after reduced intensity allogeneic hematopoietic cell transplantation. Bone marrow 
transplantation. Dec 2007;40(11):1027-1032. 
7. 
Eapen M, Giralt SA, Horowitz MM, et al. Second transplant for acute and chronic leukemia 
relapsing after first HLA-identical sibling transplant. Bone marrow transplantation. Oct 
2004;34(8):721-727. 
8. 
Bejanyan N, Weisdorf DJ, Logan BR, et al. Survival of patients with acute myeloid leukemia 
relapsing after allogeneic hematopoietic cell transplantation: a center for international blood and 
marrow transplant research study. Biology of blood and marrow transplantation : journal of the 
American Society for Blood and Marrow Transplantation. Mar 2015;21(3):454-459. 
9. 
Bachireddy P, Hainz U, Rooney M, et al. Reversal of in situ T-cell exhaustion during effective 
human antileukemia responses to donor lymphocyte infusion. Blood. Feb 27 2014;123(9):1412-
1421. 
10. 
Chang X, Zang X, Xia CQ. New strategies of DLI in the management of relapse of hematological 
malignancies after allogeneic hematopoietic SCT. Bone marrow transplantation. Mar 
2016;51(3):324-332. 
11. 
Zeidan AM, Forde PM, Symons H, et al. HLA-haploidentical donor lymphocyte infusions for 
patients with relapsed hematologic malignancies after related HLA-haploidentical bone marrow 
transplantation. Biology of blood and marrow transplantation : journal of the American Society 
for Blood and Marrow Transplantation. Mar 2014;20(3):314-318. 
12. 
Laubach JP, Richardson PG. CD38-Targeted Immunochemotherapy in Refractory Multiple 
Myeloma: A New Horizon. Clinical cancer research : an official journal of the American 
Association for Cancer Research. Jun 15 2015;21(12):2660-2662. 

Date of protocol: 10/14/2020                                                    IRB Approval Date: 11/24/2020 
Version of protocol: 7 
IND number: 139015 
Institutional protocol number: OSU 17102 
46 
 
13. 
Lokhorst HM, Plesner T, Laubach JP, et al. Targeting CD38 with Daratumumab Monotherapy in 
Multiple Myeloma. The New England journal of medicine. Sep 24 2015;373(13):1207-1219. 
14. 
Krejcik J. Immunomodulatory Effects and Adaptive Immune Response to Daratumumab and 
Effects on T cells. Blood 2015, ASH Annual meeting2015. 
15. 
Fatehchand K, McMichael EL, Reader BF, et al. Interferon-gamma Promotes Antibody-mediated 
Fratricide of Acute Myeloid Leukemia Cells. The Journal of biological chemistry. Dec 02 
2016;291(49):25656-25666. 
16. 
Krejcik J, Casneuf T, Nijhof IS, et al. Daratumumab depletes CD38+ immune regulatory cells, 
promotes T-cell expansion, and skews T-cell repertoire in multiple myeloma. Blood. Jul 21 
2016;128(3):384-394. 
17. 
Yang Y, Wang H, Yu H, et al. IFN-gamma promotes graft-versus-leukemia effects without 
directly interacting with leukemia cells in mice after allogeneic hematopoietic cell 
transplantation. Blood. Sep 29 2011;118(13):3721-3724. 
18. 
Yang YG, Qi J, Wang MG, Sykes M. Donor-derived interferon gamma separates graft-versus-
leukemia effects and graft-versus-host disease induced by donor CD8 T cells. Blood. Jun 01 
2002;99(11):4207-4215. 
 

Date of protocol: 10/14/2020                                                    IRB Approval Date: 11/24/2020 
Version of protocol: 7 
IND number: 139015 
Institutional protocol number: OSU 17102 
47 
 
19 Appendix 
 
AML Baseline History Form 
17102_AML Baseline History Form 
 

Date of protocol: 10/14/2020                                                    IRB Approval Date: 11/24/2020 
Version of protocol: 7 
IND number: 139015 
Institutional protocol number: OSU 17102 
48 
 

Date of protocol: 10/14/2020                                                    IRB Approval Date: 11/24/2020 
Version of protocol: 7 
IND number: 139015 
Institutional protocol number: OSU 17102 
49 
 
 
17102_Bone Marrow Screening/D1 Form 
 
 

Date of protocol: 10/14/2020                                                    IRB Approval Date: 11/24/2020 
Version of protocol: 7 
IND number: 139015 
Institutional protocol number: OSU 17102 
50 
 
Concomitant Medications 
CM: THX-CTMS-REV.03A 
 
Physical Exam 
PE: THX-CTMS-REV.03A 
 
Baseline Symptoms 
BS: THX-CTMS-REV.03A 

Date of protocol: 10/14/2020                                                    IRB Approval Date: 11/24/2020 
Version of protocol: 7 
IND number: 139015 
Institutional protocol number: OSU 17102 
51 
 
 
GVHD assessment at baseline 
 
Acute GVHD 
Chronic GVHD 
Current state 
Currently active - Yes or No  
Currently active - Yes or No  
Grade 
Current grade 
Current grade 
Grade 
Maximal grade 
Maximal grade 
Prednisone  
Yes or No, dose if yes 
Yes or No, dose if yes 
Other immunosuppression 
 Yes or No 
Yes or No 
 
Vital Signs 
FA-PL: THX-CTMS-REV.03A 
 
Adverse Events 
TX: THX-CTMS-REV.03A 
No. 
Start date 
of protocol 
Adverse 
event 
description 
Toxicity 
type 
Onset 
date 
Resolution 
of event 
Grad
e 
Time of 
event 
relative 
Attribution  
Specify 
relation to 
Dose-
limiting 
toxicity 
Action 
Thera
py 
Outcom
e 

Date of protocol: 10/14/2020                                                    IRB Approval Date: 11/24/2020 
Version of protocol: 7 
IND number: 139015 
Institutional protocol number: OSU 17102 
52 
 
( AE or 
SAE) 
of 
event 
to 
treatment 
plan? 
disease 
Daratumumab, 
Transplant, 
DLI  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
EKG Form 
EKG_Form 
 

Date of protocol: 10/14/2020                                                    IRB Approval Date: 11/24/2020 
Version of protocol: 7 
IND number: 139015 
Institutional protocol number: OSU 17102 
53 
 
Hematology 
FA-HM: THX-CTMS-REV.03A 
 
Hematology, cont. 
FA-HM: THX-CTMS-REV.03A  

Date of protocol: 10/14/2020                                                    IRB Approval Date: 11/24/2020 
Version of protocol: 7 
IND number: 139015 
Institutional protocol number: OSU 17102 
54 
 
 
Blood Chemistries 
FB-BC: THX-CTMS-REV.03A 
 
Blood Chemistries, cont. 
FB-BC: THX-CTMS-REV.03A 

Date of protocol: 10/14/2020                                                    IRB Approval Date: 11/24/2020 
Version of protocol: 7 
IND number: 139015 
Institutional protocol number: OSU 17102 
55 
 
 
Serology 
FC-SR: THX-CTMS-REV.03A 

Date of protocol: 10/14/2020                                                    IRB Approval Date: 11/24/2020 
Version of protocol: 7 
IND number: 139015 
Institutional protocol number: OSU 17102 
56 
 
 
DLI Cell Infusion 
DLI_Cell_Infusion 
 
Drug Administration 
DA: THX-CTMS-REV.03A 
Start date and time 
 
Cycle and dose number 
 
Drug 
 
Lot number 
 
Dose level 
 
Route 
 
Duration 
 
 

Date of protocol: 10/14/2020                                                    IRB Approval Date: 11/24/2020 
Version of protocol: 7 
IND number: 139015 
Institutional protocol number: OSU 17102 
57 
 
17102_AML On Treatment 
17102_AML_On_Treatment 
 

Date of protocol: 10/14/2020                                                    IRB Approval Date: 11/24/2020 
Version of protocol: 7 
IND number: 139015 
Institutional protocol number: OSU 17102 
58 
 
17102 AML Response Form 
17102_AML_Response_Form