Single-Arm, Open Label, Interventional Phase II Clinical Trial Evaluating MGTA-456 in Patients With High-Risk Malignancy
Phase: PHASE2
Conditions: Acute Myeloid Leukemia, Acute Lymphocytic Leukemia, Biphenotypic/Undifferentiated Leukemia, Chronic Myelogenous Leukemia, Myelodysplasia, Relapsed Large Cell Lymphoma, Mantle Cell Lymphoma, Hodgkin Lymphoma, Burkitt Lymphoma, Relapsed T-Cell Lymphoma, Lymphoplasmacytic Lymphoma
Sponsor: Masonic Cancer Center, University of Minnesota

MT2018-06                                                          Phase II Trial of MGTA-456 for Hematologic Malignancies 
 
 
 
April 23, 2021 
Page 1 of 68 
CPRC #2018LS051 
BLOOD & MARROW TRANSPLANTION PROGRAM 
UNIVERISTY OF MINNESOTA 
 
 
 
 
SINGLE-ARM, OPEN LABEL, INTERVENTIONAL PHASE II CLINICAL TRIAL 
EVALUATING MGTA-456 IN PATIENTS WITH HIGH-RISK MALIGNANCY 
CPRC 2018LS051 
MT2018-06 
IND # 18372 
 
 
 
 
IND Sponsor:  
John E. Wagner, MD 
 
Principal Investigator:  
Margaret L. MacMillan, MD 
 
 
Lead Co-Investigator: 
Claudio Brunstein, MD, PhD 
 
Co-Investigators:  
Shernan Holtan, MD 
 
Christen Ebens, MD 
 
RadiationTherapy:  
Kathryn Dusenbery, MD  
 
MCT cGMP Facility: 
David H. McKenna, Jr., MD 
 
Biostatistician: 
Todd E. DeFor, MS 
 
Development Phase:  
2 
 
Version Date:  
April 23, 2021 
 
 
 
 
 
 
 
This document contains confidential information that is the property of the  
University of Minnesota Blood and Marrow Transplant Program 
Do not copy, disclose or circulate this protocol without written authorization from the Principal Investigator or Medical 
Directors of the University of Minnesota Medical Center-Fairview Blood and Marrow Transplant Service Line 

MT2018-06                                                          Phase II Trial of MGTA-456 for Hematologic Malignancies 
 
 
 
April 23, 2021 
Page 2 of 68 
CPRC #2018LS051 
REVISION HISTORY 
 
Revision 
# 
Version 
Date 
Summary of Changes 
Consent 
Revision 
 
04/01/2018 Original to CPRC 
 
1A 
05/02/2018 
Updated background section 2.2 with pediatric data; changed 
abbreviations MAC and NMAC to MA and NMA; section 6.4 
fixed typos per CPRC stipulations 
 
1B 
06/12/2018 
Section 4.2 & eligibility checklist – edits and corrections to 
bring study to current standard of care; schedules standard 
and research assessments edited for current standard testing 
and added research labs; minor administrative edits and 
corrections. 
 
1C 
08/13/2018 
Title page – added IND number; Section 4.2 & Eligibility 
checklist– added minimum weight requirement (>11kg);  
removed Lymphoplasmacytic lymphoma and clarified 
myelodysplastic syndrome refractory anemia;  in Section 4.4 & 
eligibility checklist – clarified ineligibility after prior autologous 
or allogeneic transplant and added additional ineligibility 
criteria added, eg patients with a HLA matched sibling and, 
patients with a HLA matched unrelated donor who is available 
at the time the transplant is needed. 
No 
1D 
08/23/2018 
Sections 2.2 and Section 2.5 - updated background section of 
the consent based on IRB stipulations and fixed typographical 
error in the inclusion criteria and eligibility checklist; changed 
references of study product from HSC835v1 to MGTA--456 
Yes 
2 
09/28/2018 
Updates made by pharmacy to conform to local standard 
clinical care: 
-Updated treatment plan and section 6 to reflect Cy to be 
given on days -7 & -6 
-Removed wording that fludarabine had to be given at 10am in 
section 6.1.1.1 and section 6.1.2.2 
-Updated Cytoxan adjusted body weight dosing calculation to 
local standard in section 6.1.1.2 
-Section 6.2.2 clarified peds MMF dosing 
- Appendix III – added Bartelink dosing nomogram table 
 
3 
12/20/2018 
Section 4.1 Updated to note that cord blood selection will be 
per Magenta’s algorithm 
Section 8 – removed 1 and 2 year chest x-ray; updated 
research labs 
Appendix III – Inpatient Pharmacy updated busulfan dosing 
and monitoring guidelines 
Consents – updated information on sponsor data use 
Yes 
3A 
01/07/2019 
Section 4.1 minor edits for clarity 
Appendix III – Inpatient Pharmacy updated busulfan dosing 
and monitoring guidelines  
Parent consent age 0-3, error correction on study calendar 
Yes 

MT2018-06                                                          Phase II Trial of MGTA-456 for Hematologic Malignancies 
 
 
 
April 23, 2021 
Page 3 of 68 
CPRC #2018LS051 
4 
04/24/2019 
Section 1.6 (Exploratory Endpoints), Section 2.6, Section 6.5, 
Section 7.3, Section 8, Section 12.2, References: Added 
Immune reconstitution sub-study in order to investigate long 
term functional immune response 
Synopsis, Section 4.1, and section 6.3: Clarified selection 
criteria and parameters of required cell dose 
Section 8, noted that chimerism will not be drawn if WBC < 
500 
Yes 
5 
11/25/2019 
Section 6.5, Section 8, - clarified that vaccinations may not be 
given if active acute or chronic GVHD or other evidence of 
poor immunologic recovery. 
Section 6.3, Section 8 – clarified cell dosing; added that there 
is no lower limit for TNC. 
Section 8 – Standard of care calendar, added Tcell subsets 
Removed Appendix I eligibility checklist, per new SOP, this 
document is kept in Oncore. 
Throughout document minor edits for consistency and clarity 
No 
6 
04/23/2021 
Dr.MacMillan takes over as principal investigator; Dr. 
Stefanski removed from study 
Yes 
 
 
 

MT2018-06                                                          Phase II Trial of MGTA-456 for Hematologic Malignancies 
 
 
 
April 23, 2021 
Page 4 of 68 
CPRC #2018LS051 
Table of Contents 
 
REVISION HISTORY .....................................................................................................................2 
LIST OF ABBREVIATIONS ...........................................................................................................8 
Protocol Synopsis ..................................................................................................................... 11 
Treatment Plan ........................................................................................................................... 13 
1 
Hypothesis and Objectives ................................................................................................ 15 
1.1 
Hypothesis .................................................................................................................... 15 
1.2 
Primary Objective.......................................................................................................... 15 
1.3 
Primary Endpoint .......................................................................................................... 15 
1.4 
Secondary Endpoints .................................................................................................... 15 
1.5 
Transplant Related Secondary Endpoints ..................................................................... 15 
1.6 
Exploratory Endpoints ................................................................................................... 15 
2 
Background ......................................................................................................................... 16 
2.1 
Overview of UCB Transplantation ................................................................................. 16 
2.1.1 
Single Unit UCBT .................................................................................................. 16 
2.1.2 
Double Unit UCBT ................................................................................................. 18 
2.1.3 
Comparisons with Other HSC Sources [12] ........................................................... 19 
2.1.4 
National BMT-CTN 0501 Study - Single versus Double UCBT [22]. ...................... 20 
2.1.5 
Impact of Conditioning on Engraftment and Survival after UCBT [23] .................... 21 
2.2 
MGTA-456 – Aryl Hydrocarbon Receptor (AHR)-Antagonist Mediated HSPC Expansion
 
22 
2.3 
Human Pharmacokinetic Data ...................................................................................... 24 
2.4 
Cryopreserved MGTA-456 ............................................................................................ 25 
2.5 
Summary and Rationale for the Proposed Study .......................................................... 25 
2.6 
Immune Reconstitution Sub-study ................................................................................ 26 
3 
Study Design ....................................................................................................................... 27 
4 
Patient Selection ................................................................................................................. 27 
4.1 
Age, Weight, Unit Cell Dose and HLA Match Criteria .................................................... 27 
4.2 
Eligible Diseases .......................................................................................................... 27 
4.3 
Organ Specific Inclusion Criteria ................................................................................... 28 
4.4 
Exclusion Criteria .......................................................................................................... 29 
5 
Patient Registration ............................................................................................................ 29 
5.1 
Registration with the Masonic Cancer Center Clinical Trials Office ............................... 29 
5.2 
.Study Enrollment with the Masonic Cancer Center Clinical Trials Office ...................... 30 

MT2018-06                                                          Phase II Trial of MGTA-456 for Hematologic Malignancies 
 
 
 
April 23, 2021 
Page 5 of 68 
CPRC #2018LS051 
5.3 
Patients Who Are Enrolled But Do Not Receive Study Treatment ................................. 30 
6 
Treatment Plan .................................................................................................................... 30 
6.1 
Conditioning Regimen (day – 8 through day -1) ............................................................ 32 
6.1.1 
TBI-Containing Regimen ....................................................................................... 32 
6.1.2 
Non-TBI-Containing Regimen................................................................................ 32 
6.2 
Immunoprophylaxis ....................................................................................................... 33 
6.2.1 
Tacrolimus ............................................................................................................. 33 
6.2.2 
Mycophenolate Mofetil........................................................................................... 33 
6.3 
MGTA-456 Infusion ....................................................................................................... 34 
6.4 
Hematopoietic Growth Factor and Other Supportive Care ............................................ 34 
6.5 
Immunizations (Immune Reconstitution Sub-study) ...................................................... 35 
6.6 
Duration of Study Participation ...................................................................................... 35 
7 
Expected Treatment Related Toxicities ............................................................................. 35 
7.1 
Potential Toxicities of the Conditioning Regimen .......................................................... 35 
7.2 
Potential Toxicities of GVHD Immunoprophylaxis and G-CSF ...................................... 38 
7.3 
Potential Side effects of Immunizations ......................................................................... 38 
7.4 
Potential Adverse Events (AE) associated with the Infusion of Cryopreserved HSPC 
Products (including MGTA-456) ............................................................................................... 39 
7.5 
Recommended Treatment of Adverse Events ............................................................... 39 
7.5.1 
Slow Engraftment/Graft Failure ............................................................................. 39 
7.5.2 
Anemia .................................................................................................................. 40 
7.5.3 
Thrombocytopenia ................................................................................................. 40 
7.5.4 
Nutrition ................................................................................................................. 40 
7.5.5 
Acute GVHD .......................................................................................................... 40 
7.5.6 
Infusional Reaction ................................................................................................ 40 
7.5.7 
Engraftment Syndrome/Transfusion Related Acute Lung Injury (TRALI) ............... 41 
8 
Schedule of Patient Activities ............................................................................................ 41 
9 
Adverse Event Monitoring, Recording and Reporting ..................................................... 47 
9.1 
Definitions ..................................................................................................................... 47 
9.2 
Adverse Event Monitoring, Recording and Reporting .................................................... 48 
9.2.1 
Event Monitoring ................................................................................................... 48 
9.2.2 
Event Recording/Documentation ........................................................................... 48 
9.2.3 
Event Reporting to the IRB, FDA and Cancer Center ............................................ 48 
9.3 
Monitoring for Stopping Rule Events ............................................................................. 49 

MT2018-06                                                          Phase II Trial of MGTA-456 for Hematologic Malignancies 
 
 
 
April 23, 2021 
Page 6 of 68 
CPRC #2018LS051 
10 
Study Data Collection and Monitoring ........................................................................... 49 
10.1 
Data Management ........................................................................................................ 49 
10.2 
Case Report Forms ....................................................................................................... 50 
10.3 
Data and Safety Monitoring Plan ................................................................................... 50 
10.4 
IND Annual Reports ...................................................................................................... 51 
10.5 
Data Sharing with Magenta ........................................................................................... 51 
10.6 
Monitoring ..................................................................................................................... 51 
10.7 
Study Record Retention ................................................................................................ 51 
11 
Definition of Study Endpoints ........................................................................................ 52 
11.1 
Neutrophil Recovery ..................................................................................................... 52 
11.2 
Platelet Recovery .......................................................................................................... 52 
11.3 
Engraftment .................................................................................................................. 52 
11.4 
Graft Failure .................................................................................................................. 52 
11.5 
Graft-versus-Host Disease ............................................................................................ 52 
11.6 
Transplant-Related Mortality ......................................................................................... 53 
11.7 
Relapse ........................................................................................................................ 53 
11.8 
Non-Catheter Associated Bacterial Infection ................................................................. 53 
11.9 
Event Free Survival (EFS) ............................................................................................ 53 
12 
Statistical Considerations ............................................................................................... 53 
12.1 
Study Design, Objectives and Endpoints ...................................................................... 53 
12.1.1 
Primary Endpoint ................................................................................................... 54 
12.1.2 
Secondary and Transplant Related Secondary Endpoints ...................................... 54 
12.1.3 
Exploratory Endpoints ............................................................................................ 54 
12.2 
Statistical Analysis ........................................................................................................ 54 
12.3 
Rationale for Sample Size ............................................................................................. 55 
12.4 
Monitoring Guidelines ................................................................................................... 55 
12.5 
Gender and Ethnicities Statement ................................................................................. 56 
13 
Conduct of the Study ...................................................................................................... 56 
13.1 
Good Clinical Practice ................................................................................................... 56 
13.2 
Ethical Considerations .................................................................................................. 56 
13.3 
Informed Consent ......................................................................................................... 56 
14 
References ....................................................................................................................... 57 
Appendix I – Karnofsky and Lansky Scales ............................................................................. 61 
Appendix II - Recommended TBI Guidelines ........................................................................... 62 

MT2018-06                                                          Phase II Trial of MGTA-456 for Hematologic Malignancies 
 
 
 
April 23, 2021 
Page 7 of 68 
CPRC #2018LS051 
Appendix III – Busulfan Dose Selection, AUC Monitoring and Algorithm for Dose 
Modification Using Once Daily IV Dosing ................................................................................ 63 
Appendix IV - GVHD Scoring ..................................................................................................... 67 
Appendix V – Targeted Toxicities ............................................................................................. 68 
 
 
 
 
 
 
 
 
 
 
 
 
 
Sponsor 
John E. Wagner, MD 
Director and Professor 
Division of Blood and Marrow Transplantation 
Department of Pediatrics 
660 Cancer Research Building 
425 East River Road 
Minneapolis, MN 55455 
612 626-2961 (phone) 
612 626-4074 (fax) 
wagne002@umn.edu (email) 
 
Principal Investigator/Contact Information: 
Margaret L. MacMillan, MD, MSc, FRCPC 
Professor of Pediatrics 
Blood and Marrow Transplantation & Cellular 
Therapy Program  
University of Minnesota  
MMC 484   
420 Delaware Street SE 
Minneapolis, MN 55455 
612 626-2961 (phone) 
612-626-2815 (fax) 
macmi002@umn.edu (email) 
Lead Co- Investigator/Contact Information: 
Claudio Brunstein, MD, PhD  
Associate Professor 
Division 
of 
Hematology, 
Oncology 
and 
Transplantation 
Department of Medicine 
Mayo Mail Code 480 
420 Delaware Street SE 
Minneapolis, MN 55455 
612 625-3918 (phone) 
612 899-6170 (pager) 
bruns072@umn.edu 
 
 
 

MT2018-06                                                          Phase II Trial of MGTA-456 for Hematologic Malignancies 
 
 
 
April 23, 2021 
Page 8 of 68 
CPRC #2018LS051 
LIST OF ABBREVIATIONS 
ABBREVIATION 
DEFINITION 
AE 
 
ADVERSE EVENT 
aGVHD 
ACUTE GRAFT VERSUS HOST DISEASE 
AHR 
 
ARYL HYDROCARBON RECEPTOR 
ALL 
ACUTE LYMPHOCYTIC LEUKEMIA 
ALT 
ALANINE AMINOTRANSFERASE 
AML 
ACUTE MYELOCYTIC LEUKEMIA 
ANC 
ABSOLUTE NEUTROPHIL COUNT 
AST 
ASPARTATE AMINOTRANSFERASE 
ATG 
ANTITHYMOCYTE GLOBULIN 
AUCcum 
CUMULATIVE AREA UNDER THE PLASMA CONCENTRATION-TIME CURVE 
AUC 
AREA UNDER THE PLASMA CONCENTRATION-TIME CURVE 
AUC∞  
AREA UNDER THE PLASMA CONCENTRATION-TIME CURVE FROM TIME ZERO TO INFINITY 
AUClast  
AREA UNDER THE PLASMA CONCENTRATION-TIME CURVE FROM TIME ZERO TO TIME OF LAST 
MEASURABLE CONCENTRATION 
BMT 
BONE MARROW TRANSPLANT 
BU 
BUSULFAN 
CBU 
CORD BLOOD UNIT 
CFR 
CODE OF FEDERAL REGULATIONS 
cGVHD 
CHRONIC GRAFT VERSUS HOST DISEASE 
CLIA 
CLINICAL LABORATORY IMPROVEMENT AMENDMENT 
Cmax  
MAXIMUM OBSERVED CONCENTRATION 
CML 
CHRONIC MYELOGENOUS LEUKEMIA 
CMV 
CYTOMEGALOVIRUS 
COBLT 
CORD BLOOD TRANSPLANT CONSORTIUM 
CRF 
CASE REPORT FORM 
CsA 
CYCLOSPORINE A 
CTCAE 
COMMON TOXICITY CRITERIA ADVERSE EVENT 
CTO 
CLINICAL TRIALS OFFICE 
CY 
CYCLOPHOSPHAMIDE 
DNA 
DEOXYRIBONUCLEIC ACID 
DMC 
DATA MONITORING COMMITTEE 
DUCBT 
DOUBLE UMBILICAL CORD BLOOD TRANSPLANTATION 
ECG 
ELECTROCARDIOGRAM 
EBV 
 
EPSTEIN-BARR VIRUS 
EFS 
EVENT FREE SURVIVAL 
FLU 
FLUDARABINE 
FDA 
FOOD AND DRUG ADMINISTRATION 
GCP 
GOOD CLINICAL PRACTICE 

MT2018-06                                                          Phase II Trial of MGTA-456 for Hematologic Malignancies 
 
 
 
April 23, 2021 
Page 9 of 68 
CPRC #2018LS051 
ABBREVIATION 
DEFINITION 
G-CSF 
GRANULOCYTE-COLONY STIMULATING FACTOR 
GVHD 
GRAFT VERSUS HOST DISEASE 
HBcAb 
HEPATITIS B CORE ANTIBODY 
HBsAg 
HEPATITIS B SURFACE ANTIGEN 
hCG 
HUMAN CHORIONIC GONADOTROPIN 
HCV 
HEPATITIS C VIRUS 
HIV 
HUMAN IMMUNODEFICIENCY VIRUS 
HLA 
HUMAN LEUKOCYTE ANTIGEN 
HSC 
HEMATOPOIETIC STEM CELLS 
HSCT 
HEMATOPOIETIC STEM CELL TRANSPLANTATION 
HSV 
HERPES SIMPLEX VIRUS 
HTLV1/2 
HUMAN T CELL LYMPHOTROPIC VIRUS 1/2 
IB 
INVESTIGATOR’S BROCHURE 
ICF 
INFORMED CONSENT FORM 
ICH 
INTERNATIONAL COUNCIL ON HARMONIZATION 
IEC 
INDEPENDENT ETHICS COMMITTEE 
IRB 
INSTITUTIONAL REVIEW BOARD 
IUD 
INTRAUTERINE DEVICE 
IUS 
INTRAUTERINE SYSTEM 
IV 
INTRAVENOUS 
LDH 
LACTATE DEHYDROGENASE 
LFT 
LIVER FUNCTION TEST 
LLOQ 
LOWER LIMIT OF QUANTIFICATION 
LMW 
LOW MOLECULAR WEIGHT 
LVEF 
LEFT VENTRICULAR EJECTION FRACTION 
MA 
MYELOABLATIVE CONDITIONING 
Magenta 
MAGENTA THERAPEUTICS, INC. 
MDS 
MYELODYSPLASTIC SYNDROME 
MFI 
MEAN FLUORESCENCE INTENSITY 
MedDRA 
MEDICAL DICTIONARY FOR REGULATORY ACTIVITIES 
MMF 
MYCOPHENOLATE MOFETIL 
MSD 
MATCHED SIBLING DONOR 
NC 
NUCLEATED CELLS 
NMA 
NON-MYELOABLATIVE CONDITIONING 
NOAEL 
NO OBSERVED ADVERSE EFFECT LEVEL 
PES 
PRE-ENGRAFTMENT SYNDROME 

MT2018-06                                                          Phase II Trial of MGTA-456 for Hematologic Malignancies 
 
 
 
April 23, 2021 
Page 10 of 68 
CPRC #2018LS051 
ABBREVIATION 
DEFINITION 
PFT 
PULMONARY FUNCTION TEST 
PK 
PHARMACOKINETIC 
PBMC 
PERIPHERAL BLOOD MONONUCLEAR CELLS 
SAB 
SINGLE ANTIGEN BEAD 
SAE 
SERIOUS ADVERSE EVENT 
SOP 
STANDARD OPERATING PROCEDURE 
SR-1 
STEMREGENIN-1 
SUCBT 
SINGLE UMBILICAL CORD BLOOD TRANSPLANTATION 
TBI 
TOTAL BODY IRRADIATION 
TCF 
TOTAL BODY IRRADIATION, CYCLOPHOSPHAMIDE, FLUDARABINE CONDITIONING 
TEAE 
TREATMENT-EMERGENT ADVERSE EVENTS 
TKI 
TYROSINE KINASE INHIBITOR 
TRALI 
TRANSFUSION-RELATED ACUTE LUNG INJURY 
TNC 
TOTAL NUCLEATED CELL 
TREC 
T CELL RECEPTOR EXCISION CIRCLES 
TRM 
TRANSPLANT-RELATED MORTALITY 
UCB 
UMBILICAL CORD BLOOD 
UCBT 
UMBILICAL CORD BLOOD TRANSPLANT 
ULN 
UPPER LIMIT OF NORMAL 
US 
UNITED STATES 
WHO 
WORLD HEALTH ORGANIZATION 
 
 

MT2018-06                                                          Phase II Trial of MGTA-456 for Hematologic Malignancies 
 
 
 
April 23, 2021 
Page 11 of 68 
CPRC #2018LS051 
Protocol Synopsis 
SINGLE-ARM, OPEN LABEL, INTERVENTIONAL PHASE II CLINICAL TRIAL EVALUATING 
MGTA-456 IN PATIENTS WITH HIGH-RISK MALIGNANCY 
Study Design: 
This is an single arm, open label, interventional phase II trial evaluating the 
efficacy of umbilical cord blood (UCB) hematopoietic stem and progenitor cells 
(HSPC) expanded in culture with stimulatory cytokines (SCF, Flt-3L, IL-6 and 
thromopoietin) in the presence of an aryl hydrocarbon receptor antagonist, 
LHD221, on lympho-hematopoietic recovery.  Patients will receive a uniform 
myeloablative conditioning and post-transplant immunoprophylaxis. 
Investigational 
Agent: 
MGTA-456 is the cellular product composed of the UCB hematopoietic stem and 
progenitor cells after expansion culture in the presence of the low molecular 
compound LHD221 and its companion CD34 depleted fraction. 
Primary 
Objective: 
Determine if transplantation of MGTA-456 significantly reduces the expected 
duration of neutropenia and number of hospital days to day 100 relative to that 
observed in recipients of an unmanipulated single UCB unit 
Primary 
Endpoint: 
Incidence of neutrophil recovery by day 14 
Secondary 
Endpoints: 
• Number of days alive without hospitalization between days 0 and 100 after 
transplantation 
• Incidence of secondary graft failure 
• Incidence of platelet recovery at day 42 
• Incidence of transplant-related mortality (TRM) at 6 months 
Transplant 
Related 
Secondary 
Endpoints: 
• Incidence of grades II-IV and III-IV acute graft vs host disease (GVHD) at day 
100 
• Incidence of chronic GVHD at 1 year 
• Incidence of relapse at 2 years 
• Incidence of non-catheter associated bacterial infections by day 100 
• Probability of overall survival and event-free survival (EFS) at 2 years 
Exploratory 
Endpoints: 
• Description of immunological recovery 
• Incidence of absolute CD4 T cell ≥0.2 x 109/L by day 100 
• Incidence of opportunistic infection (viral/fungal) by day 100 
• Description of hospital costs by day 100 
• Description of number of red cell and platelet transfusions by day 100 
• Assess B and T cell immune reconstitution as well as functional responses at 
day 100 and day 180 
Eligible 
Diseases: 
Acute myeloid leukemia (AML) 
Acute lymphocytic leukemia (ALL) 
Biphenotypic/undifferentiated leukemia 

MT2018-06                                                          Phase II Trial of MGTA-456 for Hematologic Malignancies 
 
 
 
April 23, 2021 
Page 12 of 68 
CPRC #2018LS051 
Chronic myelogenous leukemia excluding refractory blast crisis 
Myelodysplasia (MDS) IPSS Int-2 or High risk (i.e. RAEB, RAEBt) or other high risk
features 
 
Unit  Selection 
for Expansion 
Culture: 
Cell dose ≥1 x 107 nucleated cells per kilogram (kg) recipient body weight and 
HLA match at a minimum of 5 of 8 HLA alleles at high resolution A, B, C, DRB1 
typing- based on the current Magenta cord blood algorithm. 
 
Transplant 
HSC Product:  
Cryopreserved MGTA-456 with a cell dose  of a minimum of 1 x 106 CD34/kg but 
ideally will be 10 x 106 per kg recipient body weight and the cryopreserved CD34- 
fraction. 
Key Inclusion 
Criteria: 
Aged ≤ 55 years  
Weight >11kg 
Karnofsky performance status >70 (≥16 years) or 
Lansky Play Score >50  
Adequate organ function (per section 4.3) 
 
Key Exclusion 
Criteria: 
Available HLA matched related or unrelated donor 
Pregnancy or breastfeeding 
History of HIV infection or known HIV positive serology 
Active serious infection 
Prior autologous or allogeneic hematopoietic stem cell transplant 
 
Accrual 
Objective: 
40 patients enrolled over 3 years 
 
 
 

MT2018-06                                                          Phase II Trial of MGTA-456 for Hematologic Malignancies 
 
 
 
April 23, 2021 
Page 13 of 68 
CPRC #2018LS051 
Treatment Plan 
All patients will receive MGTA-456 on the day of transplantation after myeloablative conditioning.  
All patients aged 3-55 years will be conditioned with cyclophosphamide (CY) 120 mg/kg total 
dose, fludarabine (FLU) 75 m/m2 total dose and total body irradiation (TBI) 1320 cGy total dose 
as well as tacrolimus (Tac) and mycophenolate mofetil (MMF) immunoprophylaxis and 
granulocyte-colony stimulating factor (G-CSF) as detailed below: 
Day 
Conditioning Regimen 
Immunoprophylaxis 
Hematopoietic Growth Factor 
-8 
FLU 25 mg/m2 IV over 1 hour 
(<10 kg: 0.83 mg/kg IV over 1 hour) 
 
-7 
FLU 25 mg/m2 IV over 1 hour 
(<10 kg: 0.83 mg/kg IV over 1 hour) 
CY 60 mg/kg IV over 2 hours 
 
-6 
FLU 25 mg/m2 IV over 1 hour 
(<10 kg: 0.83 mg/kg IV over 1 hour)  
CY 60 mg/kg IV over 2 hours 
 
-5 
Rest 
 
-4 
TBI 165 cGy twice daily 
 
-3 
TBI 165 cGy twice daily 
Begin Tac / MMF (section 6.2) 
-2 
TBI 165 cGy twice daily 
 
-1 
TBI 165 cGy twice daily 
 
0 
MGTA-456 infusion 
 
+1 
 
Begin G-CSF 5 ug/kg/d until the 
absolute neutrophil count (ANC) is 
>2500/uL for 2 consecutive days 
(section 6.4) 
 
All young children <3 years of age at the time of diagnosis will receive MGTA-456 on the day of 
transplantation after a non-TBI containing myeloablative conditioning as TBI may have a 
damaging effect on brain development in the very young child.  All patients aged 0-3 years will be 
conditioned with busulfan (BU), FLU and melphalan (MEL) as well as Tac/MMF 
immunoprophylaxis and G-CSF, as detailed below: 
Day 
Conditioning Regimen 
Immunoprophylaxis 
Hematopoietic Growth Factor 
-8 
BU IV once daily with dose based on 
Pharmacokinetics (PK) calculator over 3 
hours 
 
-7 
Bu IV once daily adjusted based on PK 
results over 3 hours 
 
-6 
Bu IV once daily adjusted based on PK 
results 
 

MT2018-06                                                          Phase II Trial of MGTA-456 for Hematologic Malignancies 
 
 
 
April 23, 2021 
Page 14 of 68 
CPRC #2018LS051 
Day 
Conditioning Regimen 
Immunoprophylaxis 
Hematopoietic Growth Factor 
-5 
Bu IV once daily adjusted based on PK 
results over 3 hours 
 
-4 
FLU 25 mg/m2/day (0.83 mg/kg/day if < 10 
kg*) IV over 60 min 
MEL 50 mg/m2/day (1.7 mg/kg/day if < 10 
kg*) IV over 30 min 
 
-3 
FLU 25 mg/m2/day (0.83 mg/kg/day if < 10 
kg*) IV over 60 min 
MEL 50 mg/m2/day (1.7 mg/kg/day if < 10 
kg*) IV over 30 min 
Begin Tac / MMF (section 6.2) 
-2 
FLU 25 mg/m2/day (0.83 mg/kg/day if < 10 
kg*) IV over 60 min 
MEL 50 mg/m2/day (1.7 mg/kg/day if < 10 
kg*) IV over 30 min 
 
-1 
Rest 
 
 0 
MGTA-456 Infusion 
 
+1 
 
Begin G-CSF 5 ug/kg/d until the 
absolute neutrophil count (ANC) is 
>2500/uL for 2 consecutive days 
(section 6.4) 
*Patients <11kg are currently ineligible because of the expected volume of DMSO in thawed 
products.  Once a wash step after thawing has been validated and approved by the FDA, patients 
<11 kg may be eligible. 
 
 

MT2018-06                                                          Phase II Trial of MGTA-456 for Hematologic Malignancies 
 
 
 
April 23, 2021 
Page 15 of 68 
CPRC #2018LS051 
1 Hypothesis and Objectives 
1.1 Hypothesis 
In vitro expansion of the hematopoietic stem and progenitor cells (HSPC) obtained from a 
single umbilical cord blood (UCB) unit prior to transplantation will significantly reduce the 
number of days of neutropenia relative to that observed after the transplantation of an 
unmanipulated single UCB unit (standard of care). 
1.2 Primary Objective 
Determine if transplantation of MGTA-456 significantly reduces the expected duration of 
neutropenia and number of hospital days to day 100 relative to that observed in recipients of 
an unmanipulated single UCB unit. 
1.3 Primary Endpoint 
Determine the incidence of neutrophil recovery by day 14 after transplantation in recipients of 
MGTA-456.   
1.4 Secondary Endpoints 
• 
Number of days alive without hospitalization between days 0 and 100 after 
transplantation 
• 
Incidence of secondary graft failure 
• 
Incidence of platelet recovery at day 42 
• 
Incidence of TRM at 6 months 
1.5 Transplant Related Secondary Endpoints 
• 
Incidence of grades II-IV and III-IV acute GVHD at day 100 
• 
Incidence of chronic GVHD at 1 year 
• 
Incidence of relapse at 2 years 
• 
Incidence of non-catheter associated bacterial infections by day 100 
• 
Probability of overall survival (OS) and event-free survival (EFS) at 2 years 
1.6 Exploratory Endpoints 
Additional analyses will be performed that may be important for the design of future trials. 
These include: 
• 
Description of immunological recovery 
• 
Incidence of absolute CD4 T cell >0.2 x 109/L by day 100 
• 
Incidence of opportunistic infection (viral / fungal) by day 100 
• 
Description of hospital costs by day 100 
• 
Description of number of red cell and platelet transfusions by day 100  
• 
Assess B and T cell immune reconstitution as well as functional responses at day 100 
and day 180. 

MT2018-06                                                          Phase II Trial of MGTA-456 for Hematologic Malignancies 
 
 
 
April 23, 2021 
Page 16 of 68 
CPRC #2018LS051 
2 Background 
Hematopoietic stem cell transplantation (HSCT) is a standard treatment option for an increasing 
number of malignant and non-malignant disorders [1].  To reconstitute hematopoiesis after an 
intensive myeloablative therapy, the transplantation of hematopoietic stem cells (HSCs) is 
required.  Such HSCs are typically recovered from the bone marrow or apheresed peripheral 
blood of the patients themselves, or suitably HLA matched related and unrelated volunteer donors 
[1,2].  Unfortunately, suitable donors are frequently not available either because the patient's own 
marrow is contaminated with tumor cells or potential allogeneic marrow donors are HLA 
mismatched or not healthy enough due to preexisting co-morbidities [3].   UCB is an established 
alternative source of HSCs that is capable of reconstituting hematopoiesis after intensive 
myeloablative therapy.  It is immediately available at the time it is needed (in contrast to unrelated 
volunteer donors which takes a median of 3-4 months) and poses no risk to the donor [4,5]. 
2.1 Overview of UCB Transplantation 
As a result of the early successes with UCBT from sibling donors [6,7], pilot programs for the 
banking of unrelated donor UCB were initiated in many countries worldwide [8,9,10]. In 
addition to rapid availability, absence of donor risk, absence of donor attrition, and very low 
risk of transmissible infectious diseases, such as CMV and EBV, UCB is associated with a 
lower risk of acute GVHD despite HLA mismatch.  UCB is especially beneficial for patients of 
ethnic and racial minority descent for whom suitably matched adult marrow and blood donors 
often cannot be identified [11]. UCBT is also associated with a potent anti-leukemia effect [12, 
13, 14], lost in recipients of T cell depleted HSCs.  While there is growing interest in the use of 
HLA mismatched haploidentical related donors with promising early data using post-transplant 
cyclophosphamide (CY) [15, 16], risks of relapse and clonal hematopoiesis has been observed 
[17].  Therefore, UCB remains an important alternative particularly for children and young adults. 
The University of Minnesota has the largest single center experience worldwide with UCBT, 
having performed more than 1400 primary transplants with UCB between January 1, 1992 and 
the present. 
2.1.1 Single Unit UCBT 
2.1.1.1 
University of Minnesota Single Center Experience [18]   
Between 1994 and 2001, 102 consecutive patients (median age 7.4 years) 
received a single, unrelated UCB unit after a myeloablative conditioning for 
malignant (n = 65; 68% high-risk) and non-malignant diseases (n = 37).  The 
median infused cell dose of UCB was 3.1 x 107 nucleated (NC)/kg (range 0.7-57.9), 
and 2.8 x 105 CD34+ cells/kg (range 0.4-39.1).  Fourteen percent had an HLA 
matched unit with the remaining 86% having a mismatch at 1 to 3 HLA-antigens.  
Neutrophil recovery (defined as an absolute neutrophil count [ANC] ≥ 500/uL) 
occurred at a median of 23 days (range 9-54) with the cumulative incidence of 
engraftment of 88% (95% CI: 81-95) by day 42. Speed of neutrophil recovery and 
engraftment were strongly associated with cell dose, with markedly inferior 
engraftment (72% at a median of 34 days) in patients receiving a CD34+ cell dose 
<1.7 x 105 cells/kg.  

MT2018-06                                                          Phase II Trial of MGTA-456 for Hematologic Malignancies 
 
 
 
April 23, 2021 
Page 17 of 68 
CPRC #2018LS051 
The incidences of grade II-IV and III-IV acute GVHD were 39% (95% CI: 29-49) 
and 11% (95% CI: 5-17), respectively, at day 100, with 10% (95% CI: 4-14) of 
patients having chronic GVHD at 1 year. One year TRM was 30% (95% CI: 21-39) 
which was strongly associated with CD34+ cell dose.  The probabilities of 1 and 2-
year survival were 58% (95% CI: 49-70) and 47% (95% CI: 36-57), respectively.  
Importantly, with a graft cell dose >1.7 x 105 CD34+ cells/kg, survival was 70% 
(95% CI: 49-90) at 1 year. 
The principal conclusions of this study were: 1) a CD34 dose threshold is >1.7 x 
105/kg and nucleated cell dose threshold is >2.5 x 107/kg; 2) neutrophil recovery is 
slow at a median of 23 days with more rapid recovery in recipients of higher cell 
doses, 3) risks of acute and chronic GVHD are low despite HLA mismatch; 4) cell 
dose significantly limits the applicability of UCB, particularly in adult size recipients. 
2.1.1.2 
National COrd BLood Transplant (COBLT) Study [19] 
On the basis of promising single center results and registry reports, the National 
Heart, Lung and Blood Institute (NHLBI) proposed COBLT study, a phase 2 trial to 
determine if unrelated UCB could serve as an adequate HSC source.  The primary 
endpoint of the study was survival at 180 days after transplantation. The secondary 
endpoints included engraftment (neutrophil and platelet), acute and chronic GVHD, 
disease-free survival, long-term survival, relapse, and regimen-related toxicities. 
For children with malignancy over the age of 2 years, the conditioning regimen and 
GVHD prophylaxis consisted of TBI 1350 cGy, CY 120 mg/kg and anti-thymocyte 
globulin (ATG, equine) 90 mgkg and CsA and methylprednisolone (MP) for GVHD 
prophylaxis. 
One hundred and ninety-three children with 
hematologic malignancy were enrolled.  The 
median age was 7.7 years (range, 0.9-17.9 
years) and median weight was 25.9 kg 
(range, 7.5-118.4 kg) with 40% being 
nonwhite, 61% being male, and 51% being 
seropositive for cytomegalovirus (CMV). The 
majority of patients had either ALL (n = 109 
[57% of total patients] with 17 in first 
complete remission [CR]; 65 in second CR; 
20 in third CR; 6 in relapse; and, 1 with 
primary induction failure) or AML (n = 51 
[27%] with 13 in first CR; 21 in second CR; 6 
with primary induction failure; and 11 in 
relapse). The UCB grafts were 6/6 HLA 
matched (8.9%), 5/6 matched (30.4%) or 4/5 
matched (58.1%).  The median TNC, CD34+, 
and CD3 doses of the UCB grafts were 5.1 × 107 cells/kg (range, 1.5-23.7), 1.9 × 
105/kg (range, 0.0-25.3), and 7.9 × 106/kg (range, 0.1-35.6), respectively.  

MT2018-06                                                          Phase II Trial of MGTA-456 for Hematologic Malignancies 
 
 
 
April 23, 2021 
Page 18 of 68 
CPRC #2018LS051 
The incidence of neutrophil recovery by day 42 was 79.9% (95% confidence 
interval [CI] 75.1%-85.2%) with 14 patients recovering neutrophils between days 
43 and 90. At 6 months, 86.9% of patients had sustained neutrophil engraftment. 
The median time to neutrophil recovery was 27 days (range, 11-90 days). Primary 
and secondary graft failure occurred in 21 and 2 patients, respectively.  The 
incidence of platelet engraftment (defined as platelet count ≥ 50 000/uL without 
transfusion for 1 week) was 50.0% (95% CI, 42.1%-56.5%) at day 180. Notably, 
the probability of EFS was 49.5% at 2 years with no impact of HLA match based on 
HLA A and B at antigen level and DRB1 at allele level (Figure 1) and the 
incidences of grade II-IV acute GVHD at day 100, chronic GVHD at 2 years, and 
relapse at 2 years were 19.5%, 21% and 20%, respectively. 
In univariate analysis, lower recipient weight (p=.02), better allele level HLA match 
(p=.03), higher TNC (p=.03), and higher CD34+ dose (p=.01) positively impacted 
neutrophil recovery. In a multivariate Cox model, only better allele level HLA match 
(p=.04) and higher TNC dose were independently significant (p=.04). 
The principal conclusions of this study were: 1) slow neutrophil recovery and poor 
engraftment are significant limitations of UCBT, 2) risks of GVHD are low relative to 
other HSC sources, and 3) HLA mismatch is tolerable with improved survival in 
recipients of better HLA matched grafts with higher TNC. 
2.1.2 Double Unit UCBT   
2.1.2.1 Minnesota Pilot Experience [20, 21] 
Since cell dose was identified as a major limitation of UCBT, often preventing the 
consideration of UCB for adult recipients, we explored the possibility of infusing two 
partially HLA matched units to augment cell dose.  After 2000, two UCB units were 
increasingly utilized, particularly in adults and adolescents for whom an adequately 
dosed single UCB unit could not be identified.  The underlying hypothesis was that 
the addition of the second unit would enhance the engraftment and the speed of 
hematopoietic recovery. 
In the first pilot study [20] of double UCBT (DUCBT), 31 adult and adolescent 
patients [median age 24 years (range: 13-53); median weight 73 kg (range: 48-
120)] with high-risk hematologic malignancy were transplanted with two partially 
HLA-matched UCB units after a myeloablative conditioning. The median total 
infused dose 3.7 x 107 nucleated cells (NC) per kilogram (range 1.1-6.3) and 4.9 x 
105 CD34 per kilogram (range, 0.9-14.5). 
Of 29 patients surviving 21 days after transplant, 100% engrafted at a median of 23 
days (range 14-41), comparing favorably with 65% engraftment in the prior 23 
adults treated with a single UCBT.  The incidence of platelet recovery (>50,000/uL) 
was 73% (95% CI, 51-95) at day 180. Incidence of grades II-IV and III-IV acute 
GVHD was 65% (95% CI, 42-88) and 17% (95% CI, 2-32) at day 100.  EFS was 
72% at 1 year for patients transplanted in CR. 

MT2018-06                                                          Phase II Trial of MGTA-456 for Hematologic Malignancies 
 
 
 
April 23, 2021 
Page 19 of 68 
CPRC #2018LS051 
The principal conclusions of this study were: 1) DUCBT is safe with engraftment 
observed in all patients, 2) one unit predominates within the first 100 days, 3) 
>90% of adults will be able to identify two units that are partially HLA matched with 
the patient and each other, 4) incidence grade III-IV acute GVHD is similar to that 
observed after single UCBT; and 5) survival exceeds that of historical data in adult 
recipients of a single UCB unit. 
2.1.3 Comparisons with Other HSC Sources [12] 
In order to determine the relative effectiveness of DUCBT compared to other HSC sources 
(marrow or peripheral blood from matched and mismatched sibling and unrelated donors), 
consecutive patients aged ≥ 10 years and undergoing first allogeneic HSCT for 
hematologic malignancy were evaluated. All 536 patients received myeloablative 
conditioning with CY 120 mg/kg and TBI 1200 to 1320 cGy with the addition of FLU 75 
mg/m2 in recipients of DUCBT; GVHD immunoprophylaxis included a calcineurin inhibitor. 
Allografts were from a matched unrelated donor (MRD, n=204), matched unrelated donor 
(MUD, n=152), mismatched unrelated donor (MMUD, n=52), or DUCB (n=128). 
Differences between donor groups included, higher median age in MRD recipients, more 
frequent diagnosis of CML in recipients of MUD or MMUD grafts, lower incidence of CMV 
seropositivity in recipients of MUD grafts, and greater HLA mismatch and shorter follow-up 
in recipients of DUCB. 
The primary endpoint of this analysis was leukemia free survival (LFS). LFS at 5 years 
was similar for all 4 groups. After adjusting for disease risk and time from diagnosis to 
transplantation, multivariable analysis did not 
reveal any difference in the relative risk of 
EFS by donor type. 
The incidence of relapse at 5 years was 
comparable in recipients of MRD, MUD, and 
MMUD grafts but lower in recipients of 
DUCBT (Figure 2) with similar outcomes in 
the subset of patients ≤ 45 years. After 
adjusting for disease risk, interval from 
diagnosis to transplantation, age at 
transplantation and diagnosis, multivariable 
analysis showed lower relative risk of relapse 
was associated with DUCBT. Similarly, the 
relative risk of relapse remained lower 
among DUCBT recipients regardless of risk 
group and additional analyses revealed 
similar outcomes when restricted to patients 
aged ≥18 years. Leukemia relapse was the 
most frequent cause of mortality in recipients 
of MRD, MUD, and MMUD grafts. 

MT2018-06                                                          Phase II Trial of MGTA-456 for Hematologic Malignancies 
 
 
 
April 23, 2021 
Page 20 of 68 
CPRC #2018LS051 
The incidence of TRM at 2 years, however, was higher in recipients of UCB even after 
adjusting for age at transplantation and diagnosis. Analysis of risk factors for TRM among 
DUCB recipients demonstrated a higher risk in patients with delayed neutrophil recovery 
(41% [95% CI, 26%-56%] if neutrophil recovery took ≥26 days (which was the median time 
to neutrophil recovery) compared 16% [95% CI, 7%-25%] if recovery was <26 days). If 
restricted to DUCB recipients with earlier (<median 26 days) neutrophil recovery after 
UCBT, the incidence of TRM was similar in all groups, emphasizing that delayed 
engraftment is the single greatest barrier to successful UCBT and the most important 
contributor to early TRM. Infection was the most common cause of death among recipients 
of UCB. 
The principal conclusions of this study were: 1) Higher TRM after DUCBT is still driven by 
prolonged neutropenia, and 2) relapse is low after DUCBT relative to other HSC sources.  
2.1.4 National BMT-CTN 0501 Study - Single versus Double UCBT [22]. 
As a result of these promising single institutional data, a national trial was developed to 
compare single versus DUCBT to determine if two UCB units would confer a survival 
advantage. Between December 1, 2006, and February 24, 2012, a total of 224 patients 1 
to 21 years of age with hematologic cancer were randomly assigned to undergo DUCBT 
(111 patients) or single UCBT (113 patients) after a uniform myeloablative conditioning 
regimen regimen of FLU 75 mg/m2, TBI 1320 cGy and CY 120 mg/kg. The primary end 
point was 1-year overall survival. Treatment groups were balanced with respect to all 
baseline covariates, including sex, age, results of serologic testing for cytomegalovirus, 
disease type and status at transplantation, performance score, degree of donor–recipient 
HLA matching and ABO matching, and self-reported Hispanic or Latino background and 
race or ethnic group. The median age at transplantation was 9.9 years (range, 1.1 to 21.2) 
for DUCBT recipients and 10.4 years (range, 1.4 to 21.4) for single UCBT recipients, and 
the median body weight was 37.0 kg (range, 9.7 to 81.7) and 35.7 kg (range, 10.0 to 93.0), 
respectively. All received a graft containing >2.5 x 107 NC/kg.  The median number of 
infused NC/kg was 7.2 x 107 for recipients of DUCBT and 3.9 x 107 for recipients of single 
UCBT grafts, and the number of infused CD34+ cells/kg was 3.7 x 105 and 1.9 x 105, 
respectively. 
The overall survival rate was 65% (95% CI, 56 to 74) among DUCBT recipients and 73% 
(95% CI, 63 to 80) among single UCBT recipients (p=0.17). In a multivariate analysis, the 
risk of death did not differ significantly between recipients of DUCBT and recipients of 
single UCBT (hazard ratio, 1.34; 95% CI, 0.86 to 2.09; p=0.20, with the single-unit group 
used as the referent), even after adjustment for disease type (AML vs. other), which was 
the only factor associated with an increased risk of death. 
The 1-year EFS rate was 64% (95% CI, 54 to 72) among DUCBT recipients and 70% 
(95% CI, 60 to 77) among single UCBT recipients (p=0.11). In a multivariate analysis, the 
risk of relapse or death (i.e., the risk of treatment failure, the inverse of the EFS rate) did 
not differ significantly between groups, even after adjustment for leukemia type, self-

MT2018-06                                                          Phase II Trial of MGTA-456 for Hematologic Malignancies 
 
 
 
April 23, 2021 
Page 21 of 68 
CPRC #2018LS051 
reported race (white vs. nonwhite), and HLA match score (better HLA match had worse 
outcome), which were the factors associated with EFS.  
Notably, the incidence of neutrophil recovery was 88% (95% CI, 82 to 94) among DUCBT 
recipients and 89% (95% CI, 83 to 95) among single UCBT recipients (p=0.29), at a 
median of 23 days (range, 11 to 133) and 21 days (range, 11 to 62) after transplantation, 
respectively. No patients in either group had secondary graft failure. The incidence of 
platelet recovery, however, was significantly higher and recovery occurred more quickly 
among recipients of a single UCBT than among recipients of a DUCBT (incidence, 76% 
[95% CI, 68 to 85] vs. 65% [95% CI, 56 to 74]; P=0.04). The median time to platelet 
recovery was 58 days (range, 28 to 295) in the single unit group and 84 days (range, 22 to 
716) in the double-unit group. 
For the other endpoints, the incidence of grade II–IV acute GVHD was similar in the two 
treatment groups (p=0.78); however, recipients of DUCBT had a higher incidence of grade 
III and IV acute GVHD (23% [95% CI, 15 to 31] vs. 13% [95% CI, 7 to 20], p=0.02). The 
incidence of any chronic GVHD at 1 year was 32% (95% CI, 23 to 40) and 30% (95% CI, 
22 to 39), respectively (p=0.51), with a higher incidence of extensive disease (15% [95% 
CI, 8 to 22] vs. 9% [95% CI, 4 to 14], respectively p=0.05).  Among the 220 patients (91%) 
with at least one infection after transplant, 120 (55%) had a severe infection, and 32 (15%) 
had a life-threatening or fatal infection. No significant differences were observed between 
the treatment groups.  The incidences of relapse and TRM were also similar in the two 
treatment groups. Notably, the incidence of relapse at 1 year was low in both groups: 14% 
(95% CI, 7 to 21) in recipients of a DUCBT and 12% (95% CI, 6 to 18) in recipients of a 
single UCBT (p=0.12). The incidence of TRM at 1 year was 22% (95% CI, 14 to 30) 
among DUCBT recipients and 19% (95% CI, 11 to 26) among single UCBT recipients 
(p=0.43). 
The principal conclusions of this study were: 1) rates of engraftment, relapse and survival 
were similar between recipients of DUCBT and an adequately dosed single UCBT, and 2) 
patients in both treatment groups had better engraftment and survival outcomes than 
those previously reported, supporting the use of FLU rather than ATG in the conditioning, 
and MMF rather than methylprednisolone in the post-transplant immunoprophylaxis in 
future trials. 
2.1.5 Impact of Conditioning on Engraftment and Survival after UCBT [23] 
The BMT CTN 0501 trial not only demonstrated similar survival rates in recipients of 
double vs single UCBT in children with hematologic malignancies but suggested that the 
treatment package, ie conditioning and post-transplant immunoprophylaxis, might be 
superior to other regimens.  This prompted a comparison of survival of 0501 trial versus 
nontrial patients to determine the generalizability of trial results and whether survival was 
better because of the trial treatment regimen. During the trial period, 396 recipients of a 
single UCB unit met trial eligibility but were not enrolled. Trial patients (n = 100) received 
TBI 1320 cGy, CY120 mg/kg, and FLU 75 mg/m2 (TCF). Non-trial patients either received 
the same TCF regimen (n = 62; nontrial TCF) or alternative regimens 

MT2018-06                                                          Phase II Trial of MGTA-456 for Hematologic Malignancies 
 
 
 
April 23, 2021 
Page 22 of 68 
CPRC #2018LS051 
(n = 334; nontrial regimens). Five-year survival between trial and nontrial patients 
conditioned with TCF was similar (70% versus 62%) (Figure 3). However, 5-year survival 
was significantly lower with nontrial TBI-containing (47%; hazard ratio [HR], 1.97; P = 
.001) and chemotherapy-only regimens (49%; HR, 1.87; P = .007).  The survival difference 
between the trial-specified regimen and other regimens indicate the importance of the 
treatment package for UCBT.  
The principal conclusions of this study were: 1) engraftment was better in recipients of 
TCF as 
compared to 
non-TCF 
regimens, and 
2) extended 
survival 
outcomes to 5 
years for 
patients treated 
on BMT CTN 
0501 was 
stable at 70%.  
Together, 
these data 
support the use 
of TCF as 
employed in BMT CTN 0501 developed at the University of Minnesota and used in all 
UCBT after 2000. 
2.2 MGTA-456 – Aryl Hydrocarbon Receptor (AHR)-Antagonist Mediated HSPC 
Expansion  
 
StemRegenin-1 (SR-1) was first identified in an unbiased screen for compounds that 
promoted expansion of CD34+ hematopoietic progenitors [25].  SR-1 is an AHR antagonist 
which impedes HSC differentiation during cytokine-driven expansion culture. Thus far, 36 
patients with hematological malignancy have been treated with UCB CD34+ cells after a 15-
day expansion culture using this strategy (cross-reference IND# 14822 Novartis Sponsor).  
The cellular product that results from this expansion culture as well as its companion CD34 
depleted fraction (cryopreserved on the day the CD34+ cells are placed in expansion culture), 
was previously referred to as HSC835 and is now referred to as ‘MGTA-456’. MGTA-456 has 
been tested in 2 human studies in patients with hematologic malignancies Study 
CHSC835X2201 and Study CHSC835X2202. 
Study CHSC835X2201 was a first-in-human, single-arm, single-center, open-label, proof-of-
concept study to evaluate the safety, tolerability, and preliminary efficacy of infusing MGTA-
456 (expanded UCB HSC) in patients with hematological malignancies who have undergone 
myeloablative conditioning. The conditioning regimen comprised fludarabine administered at 

MT2018-06                                                          Phase II Trial of MGTA-456 for Hematologic Malignancies 
 
 
 
April 23, 2021 
Page 23 of 68 
CPRC #2018LS051 
25 mg/m2/day i.v. for three days (Day -8 to -6), cyclophosphamide administered at 60 
mg/kg/day for two days (Day -7 to -6) and total body irradiation (TBI) at 165 cGy given twice 
daily for four days (Day -4 to -1). The study initially enrolled adult patients who were 
administered a DUCBT - one unit consisting of unmanipulated cells and the other of the 
expanded MGTA-456 product. After the first planned interim analysis at which five evaluable 
patients demonstrated that administration of MGTA-456 showed no unexpected infusional 
toxicity and resulted in hematopoietic reconstitution within the expected time frame, the 
protocol was amended to include pediatric patients (≥ 10 years) into the study. A subsequent 
interim review of the data for the first nine adult patients showed that the safety findings were 
consistent with the published findings for DUCBT [12]. The expanded cord blood product led 
to sustained, long-term hematopoietic engraftment in an accelerated fashion that correlated 
with the CD34+ cell dose. Furthermore, patients in whom MGTA-456 predominated recovered 
their neutrophils faster than patients in whom the unmanipulated CBU predominated. 
Following this, the protocol was amended such that adult patients were transplanted with a 
SUCBT with MGTA-456. Once safety data of SUCBT in adults and of DUCBT in the pediatric 
population were available, the protocol was amended such that pediatric patients were 
transplanted with SUCBT. A total of 31 patients were enrolled in this study; 27 of whom were 
transplanted during the study and 16 of whom completed the study. 
In the initial analysis of the trial identified by CHSC835X2201, 18 patients were treated with 
MGTA-456 along with a second unmanipulated UCB unit, in case the MGTA-456 did not 
engraft.  All 18 patients engrafted at a median of 14.5 days (range, 7-23 days), substantially 
better than identically treated historical controls (n=151) in whom the incidence of engraftment 
was 89% (95% CI 83-93) at a median of 23 days (range, 19-31 days) (p<0.01).  
In two Phase 2 clinical trials using MGTA-456 as a stand-alone graft, 18 patients with high-risk 
hematologic malignancy and a partially HLA matched UCB unit were treated.  Patients 
received the CD34-positive fraction along with the CD34-negative fraction of the expanded 
UCB unit which was separated prior to initiating the expansion culture. It is known that CD34-
negative cells contain CD3+ T lymphocytes and have been shown to be important in unit 
predominance long term and therefore may have a protective effect.    Nine were treated with 
myeloablative (MA) conditioning consisting of CY 120 mg/kg, FLU 75 mg/m2 and TBI 1320 
cGy, which was an extension of CHSC835X2201 and 9 were treated with non-myeloablative 
(NMA) conditioning consisting of CY 50 mg/kg, FLU 200 mg/m2 and TBI 200 cGy, identified 
by CHSC835X2202 with all receiving CsA and MMF immunoprophylaxis.  
The AHR antagonist expansion culture yielded a median of 1,227 x 106 CD34+ cells (range, 
201-8969) as compared to the input number of 4.2 x 106 (range, 1.4-16.3) after CD34 
selection – a 324-fold (range, 42-1643) expansion of CD34+ cells. As transplant results vary 
by intensity of the conditioning regimen, patient outcomes were compared to similarly treated 
historical cohorts (n=151 MA conditioning; 32 NMA conditioning). For both groups, 
demographics were similar except for more recent year of transplant for recipients receiving 
MGTA-456. For recipients of MA, MGTA-456 engrafted in 100% of patients at a median of 14 
days (range, 7-32 days) as compared to 89% engraftment at a median of 23 days in historical 
cohort (range, 19-31 days) (p<0.01). Similar to the historical cohort, complete chimerism was 

MT2018-06                                                          Phase II Trial of MGTA-456 for Hematologic Malignancies 
 
 
 
April 23, 2021 
Page 24 of 68 
CPRC #2018LS051 
rapid for both myeloid and T cells with no late graft failures in recipients of MGTA-456.  For 
recipients of NMA conditioning, MGTA-456 also engrafted in 100% of patients but at a median 
of 7 days (range, 6-14 days) as compared to 95% of patients at a median of 15 days (range, 
7-22 days) in the   historical cohort. In contrast to MA conditioning, chimerism was often mixed 
for the first month in both myeloid and T cells after NMA conditioning.  Compared to the 
historical cohort, recipients of MGTA-456 had more rapid chimerism after NMA conditioning. 
CD34 cell dose correlated with speed of recovery but only in recipients with MA conditioning; 
in recipients of non-MA conditioning, recovery was uniformly rapid regardless of CD34 cell 
dose. With regard to other transplant outcomes, results are encouraging. For recipients of 
MGTA-456 compared to the historical cohort after MA conditioning, incidence of AGVHD 3-4 
was 22% vs 24%; CGVHD, 11% vs 21%; TRM, 11% vs 34%; and OS, 67% vs 55%). After 
NMA conditioning, results are similar between cohorts, specifically, incidences of acute GVHD 
3-4 were 56% vs 15%; CGVHD, 0% vs 19%; TRM, 22% vs 20%; and OS, 44% vs 49%).   
2.3 Human Pharmacokinetic Data 
 
Patients enrolled onto Novartis study CHSC835X2201 were evaluated for the presence of the 
AHR antagonists, LFU835 or LHD221, infused with the washed cells of MGTA-456.  
Pharmacokinetic (PK) data from patients receiving MGTA-456 expanded with LFU835, 
showed an exposure to LFU835 slightly lower than predicted from animal data. Safety 
margins were very large (based on one-fifth of NOAEL in female monkeys) and maximum 
observed concentration (Cmax) and area under the plasma concentration-time curve (AUC) 
ranged from 9.9 to >10,000 ng/mL and from 68 to 2734 h × ng/mL in individual patients who 
received total cell doses between 4 and 114 million cells/kg body weight. 
For LHD221, which will be used in the present study, Table 1 shows the available results. The 
amount of co-infused LHD221 remaining on the washed cells ranged from 55 to 693 μg 
(predicted based on in vitro measurements of 0.044 pg/cell). The highest measured 
concentration in a plasma sample was 1.36 ng/mL and in many samples no LHD221 could be 
detected (lower limit of quantification [LLOQ]: 0.1 ng/mL). No pharmacokinetic parameters 
(AUC, Cmax) were derived, but compared to the exposure in female monkeys at the no 
observed adverse effect level (NOAEL) (0.5 mg/kg of LHD221; AUC=637 h × ng/mL, 
Cmax=1112 ng/mL) it can be assumed that the safety margins are very large. 
Table 1: 
LHD221 Plasma Concentrations in Patients Receiving MGTA-456 
Study ID 
Patient No. 
Calculated 
LHD221 Dose 
(μg) 
Scheduled Time (hours) 
1.0 
5.0 
12.0 
Concentration (ng/mL) 
CHSC835X2201 
0001-05123 
226 
NA 
0.00 
NA 
0001-05124 
125 
1.09 
0.17 
0.00 
0001-05126 
55 
0.00 
0.00 
0.00 
0001-05127 
203 
0.34 
0.00 
0.00 
CHSC835X2202 
1001-25101 
76 
0.00 
0.00 
0.00 

MT2018-06                                                          Phase II Trial of MGTA-456 for Hematologic Malignancies 
 
 
 
April 23, 2021 
Page 25 of 68 
CPRC #2018LS051 
Study ID 
Patient No. 
Calculated 
LHD221 Dose 
(μg) 
Scheduled Time (hours) 
1.0 
5.0 
12.0 
Concentration (ng/mL) 
1001-25102 
693 
0.14 
0.00 
0.00 
1001-25103 
169 
1.36 
0.34 
0.00 
1001-25104 
95 
0.00 
0.00 
0.00 
1001-25105 
592 
0.28 
0.00 
0.00 
For LFU835 the calculated safety margins are very large. As the LHD221 concentrations were 
very low and no PK parameters could be derived, it can be assumed that the safety margins 
are also very large for LHD221 as well.  For additional information, please refer to the IND 
Master File. 
2.4 Cryopreserved MGTA-456 
 
A manufacturing process was developed to allow the formulation of the expanded CD34+ 
fraction as a cryopreserved product. The cryopreserved product improves on the quality of key 
manufacturing reagents and results in a final product with a pre-defined volume and DMSO 
content. DMSO content in the cryopreserved product is lower in concentration than the 
amount present in the FDA-approved, cryopreserved unmanipulated UCB units. The total 
amount of administered DMSO is expected to be generally well tolerated with some risk of 
infusional toxicities. Such infusional toxicities may include but are not limited to fever, nausea, 
vomiting, excessive sweating (diaphoresis), labored breathing (dyspnea), chest discomfort, 
desaturation (reduced oxygen saturation), hypotension, hypertension, headache, and 
bradycardia (slow heart rate). If thawed product units are washed prior to infusion, the amount 
of DMSO will be significantly reduced and expected to be very well tolerated. 
2.5 Summary and Rationale for the Proposed Study 
MGTA-456 is an allogeneic UCB cell therapy product that consists of 2 cell fractions derived 
from the same UCB unit. The manufacturing process consists of expanding the CD34-positive 
(CD34+) cells derived from the UCB in vitro in the presence of cytokines and a low molecular 
weight (LMW) compound (AHR antagonist) and the resulting product is provided to the patient 
directly after the manufacturing process. The other cell fraction consists of CD34-depleted 
cells from the same UCB unit.  Results with MGTA-456 in 38 patients with hematological 
malignancies support additional evaluation. 
Therefore, we propose a phase II trial evaluating the effectiveness of MGTA-456 in children 
and adults with selected hematological malignancies eligible to receive MA conditioning. 
Eligible patients will undergo single UCBT consisting of the investigational therapy of MGTA-
456. In addition to the conventional endpoints of neutrophil and platelet engraftment, acute 
and chronic GVHD, TRM, relapse and survival, other functional endpoints, such as non-
catheter associated bacterial infections by day 100, risk of opportunistic infections, number of 
red cell and platelet transfusions will be evaluated.  Surrogate endpoints, such as number of 
hospital days and treatment costs over the first 100 days will also be evaluated.  With regard 

MT2018-06                                                          Phase II Trial of MGTA-456 for Hematologic Malignancies 
 
 
 
April 23, 2021 
Page 26 of 68 
CPRC #2018LS051 
to the primary endpoint, this trial is powered to verify the effectiveness of MGTA-456 as 
measured by the proportion of patients engrafting by day 14 after transplantation.   
This trial is supported by an NCI Program Project Grant and other local support.   Magenta 
Therapeutics will provide LHD221 (StemRegenin-1) for the proposed trial and permit use of 
the manufacturing SOPs previously developed at the University of Minnesota under 
Novartis/Magenta sponsorship as well as provide support for the manufacture of MGTA-456.   
2.6  Immune Reconstitution Sub-study 
Immunity is impaired after hematopoietic stem cell transplant (HSCT), and the recovery of cell 
counts can take years. The innate immune system is comprised of neutrophils, monocytes, 
macrophages, dendritic cells, and natural killer (NK) cells.  These cells are able to recognize 
and eradicate pathogens without the need for antigen presentation.  In contrast, the adaptive 
immune system is comprised of T and B cells.  These cells require priming by the antigen, 
leading to long-term specific responses using unique receptor sequences. The desired 
outcome of HSCT is the reestablishment of an effective immune system that accurately 
delineates self from non-self. If adequate antigen-specific immune function is present, 
functional immune reconstitution has the potential to decrease leukemic relapse and TRM. 
Clear understanding of the functional immune recovery is needed for successful HSCT. Also, 
understanding the different time courses of functional recovery of each immune cell subset 
can help to predict the course of disease in individual patients after HSCT.   
Recent work has been done to understand immune reconstitution.  In a recent study by Park 
et al (2015) 95 patients with hematologic malignancies who underwent allogeneic HSCT were 
evaluated [45].  Patients received different conditioning regimens depending on donor type 
which included sibling matched, unrelated matched or haploidentical HSCT. Lymphocyte 
subsets showed different sequential patterns according to HSCT type but no differences were 
seen according to primary diagnosis or conditioning regimen.  Specifically they found that the 
number of white blood cells (WBCs) recovered within 1 month of HSCT and T and B 
lymphocyte numbers recovered at 2 months after HSCT. Interestingly, the CD4/CD8 ratio was 
reversed during all periods after HSCT. Among T cell subpopulations, NK-T cells, and effector 
memory T cells recovered within 1–2 months after HSCT, but central memory T cells were not 
detected in peripheral blood throughout the study period.  There were low levels of naïve 
thymic T cells after HSCT, while the number of naive central T cells peaked immediately after 
HSCT. The percentage of Tregs started to increase at 3 months after HSCT, but maintained 
at a relatively low level during the entire study period.   
B cell reconstitution is less studied and understood after HSCT.  Recent work form Abdel-
Azim et al (2017) evaluated 71 pediatric patients undergoing HSCT from 2004-2011 [46].  
They found that tetanus toxoid antibody levels were normal at 1 year after HSCT whereas 
antipolysaccharide carbohydrate antibodies remained persistently low for up to 5 years. While 
naive B cell counts normalized by 6 months, IgM memory B cell deficiency persisted for up to 
2 years.  Moreover, switched memory B cell deficiency normalized by 1 year after HSCT. 
CD4+ T cell play a large part in humoral immunity; data showed the CD4 cell immune 
reconstitution correlated with that of switched memory B cells as early as 6 months after 

MT2018-06                                                          Phase II Trial of MGTA-456 for Hematologic Malignancies 
 
 
 
April 23, 2021 
Page 27 of 68 
CPRC #2018LS051 
HSCT but did not correlate with IgM memory B cells at any time point after HSCT. Taken 
together, this data suggests that antibody immune reconstitution is impaired mainly due to IgM 
memory B cell maturation block.  They also found that the use of naïve UCB was associated 
with better naive and IgM [47] memory B cell immune reconstitution at 6 months after HSCT, 
compared with the use of bone marrow and peripheral blood stem cells. Moreover, the use of 
UCB was also associated with better switched memory B cell immune reconstitution at 6 
months after HSCT, compared with the use of PBSC. As there is currently an unmet need in 
regards to understanding both B and T cell immune reconstitution as well as functional 
responses post expanded UCB HSCT this sub-study aims to prospectively assess both 
subsets of immune cells and determine functional immune responses at certain time points.   
3 Study Design 
This is a prospective single-arm, open label, interventional phase II clinical trial evaluating MGTA-
456 in children and adults with selected hematopoietic malignancies to elucidate its effect on 
reducing the duration of neutropenia and thrombocytopenia, and consequently reducing risks of 
bacterial infections and numbers of platelet transfusions, and risks of infections.  Success will be 
measured by 33% of patients achieving neutrophil recovery by day 14.  
4 Patient Selection 
Study entry is open to persons aged <55 years regardless of gender or ethnic background.  While 
there will be every effort to seek out and include females and minority patients, the patient 
population is expected to reflect those with high risk leukemia and MDS referred to the institution.  
4.1 Age, Weight, Unit Cell Dose and HLA Match Criteria 
• 
Subjects must be ≤55 years of age. 
• 
Subjects must weigh >11 kg 
• 
Subjects must have a partially HLA matched UCB unit with a pre-cryopreserved TNC 
dose >1.0 x 107 per kilogram recipient weight.  HLA matching is initially based on a 
minimum of 5 of 8 HLA alleles at high resolution A, B, C, DRB1 typing; searches will 
be performed according to the current Magenta Cord Blood Search Algorithm. 
4.2 Eligible Diseases 
• 
Acute myelogenous leukemia (AML) in morphological complete remission with: 
o Minimal residual disease (MRD) by flow cytometry, or 
o Intermediate to high risk leukemia in first (CR1) based on institutional criteria, eg. not 
favorable risk AML which is defined as having one of the following: 
- 
t(8,21) without cKIT mutation 
- 
inv(16) or t(16;16) without cKIT mutation  
- 
Normal karyotype with mutated NPM1 but FLT3-ITD wild type 
- 
Normal karyotype with double mutated CEBPA 

MT2018-06                                                          Phase II Trial of MGTA-456 for Hematologic Malignancies 
 
 
 
April 23, 2021 
Page 28 of 68 
CPRC #2018LS051 
- 
Acute promyelocytic leukemia (APL) in first molecular remission at the end of 
consolidation 
o Any second or subsequent CR, or 
o Secondary AML with prior malignancy that has been in remission for at least 12 
months. 
• 
Acute lymphocytic leukemia (ALL) at the following stages:  
o High risk first morphological, cytogenetic and molecular CR with:  
- MRD by flow cytometry, or 
- Diagnosis of Philadelphia chromosome (Ph)+ ALL, or 
- MLL rearrangement at diagnosis with slow early response at Day 14, or 
- Hypodiploidy (< 44 chromosomes or DNA index < 0.81) at diagnosis, or 
- End of induction M3 bone marrow, or 
- End of induction M2 with M2-3 at Day 42. 
o High risk second CR based on institutional criteria (eg, for children, bone marrow 
relapse <36 months from induction or T-lineage bone marrow relapse or very early 
isolated central nervous system (CNS) relapse <6 months from diagnosis, or slow 
re-induction (stage M2-3 at day 28 after induction) regardless of length remission.  
All patients with MRD by flow cytometry. 
o Any third or subsequent CR. 
• 
Secondary ALL 
• 
Biphenotypic/undifferentiated leukemia in morphological, cytogenetic and molecular CR . 
• 
Chronic Myelogenous Leukemia (CML) in high risk first chronic phase (failure of two 
tyrosine kinase inhibitors (TKI) or TKI intolerance), accelerated phase or second chronic 
phase. 
• 
Myelodysplasia (MDS) IPSS Int-2 or High risk (i.e. RAEB, RAEBt <5% blasts) or other 
high risk features, including multiple cytopenias, high risk cytogenetics or lack of 
response to standard therapy. 
• 
Relapsed large-cell lymphoma, mantle-cell lymphoma and Hodgkin lymphoma that is 
chemotherapy sensitive and ineligible for an autologous transplant.  
• 
Burkitt’s lymphoma in CR2 or subsequent CR. 
• 
Relapsed T-cell lymphoma that is chemotherapy sensitive in CR/PR that is ineligible for 
an autologous transplant. 
4.3 Organ Specific Inclusion Criteria 
• 
Karnofsky score ≥70 (16 years and older), Lansky play score >50 (children 2-16 years, 
or ‘adequate’ score for children <2 years, as detailed in Appendix I. 
• 
Adequate organ function defined as: 
o Renal: Serum creatinine within normal range for age, or if serum creatinine outside 
normal range for age, then creatinine clearance >40 ml/min or GFR normal for age 
o Hepatic: Bilirubin <3x upper limit of normal (ULN) and AST, ALT and alkaline 
phosphatase <5x ULN.  

MT2018-06                                                          Phase II Trial of MGTA-456 for Hematologic Malignancies 
 
 
 
April 23, 2021 
Page 29 of 68 
CPRC #2018LS051 
o Pulmonary function:  DLCO, FEV1, FEC (diffusion capacity) >50% of predicted 
(corrected for hemoglobin); if unable to perform pulmonary function tests, then O2 
saturation >95% on room air.  
o Cardiac:  No uncontrolled arrhythmia and left ventricular ejection fraction at rest 
must be >45%. 
• 
Available ‘back-up’ HSPC graft (e.g, second UCB unit, haploidentical related donor). 
• 
Females of child bearing potential and sexually active males must agree to use 
adequate birth control during study treatment. 
• 
Voluntary written consent signed (adult or parental) before performance of any study-
related procedure not part of normal medical care. 
4.4 Exclusion Criteria 
• 
Patients with a HLA matched sibling donor or a HLA matched unrelated donor who is 
available for marrow or peripheral blood stem cell collection at the desired time of 
transplant.  
• 
Pregnant or breast feeding. The agents used in this study may be teratogenic to a fetus 
and there is no information on the excretion of agents into breast milk.  Females of 
childbearing potential must have a blood test or urine study within 14 days prior to study 
enrollment to rule out pregnancy. 
• 
Evidence of human immunodeficiency virus (HIV) infection or known HIV positive 
serology. 
• 
Active bacterial, viral or fungal infection (currently taking medication and persistence of 
clinical signs and symptoms) with a minimum of 4 weeks of anti-fungal treatment 
• 
Prior autologous or allogeneic transplant. 
• 
Other active malignancy. 
• 
Subjects >3 years of age unable to receive TBI 1320 cGy due to extensive prior therapy 
including >12 months alkylator therapy or >6 months alkylator therapy with extensive 
radiation, or prior Y-90 ibritumomab (Zevalin) or I-131 tostumomab (Bexxar), as part of 
their salvage therapy. 
5 Patient Registration 
Registration will occur after the patient or patient’s guardian has signed the subject consent but 
before any treatment has been administered.  To be eligible for registration to this study, the 
patient must meet each criterion listed on the eligibility checklist  based on the eligibility 
assessment documented in the patient’s medical record.  A copy of the eligibility checklist is under 
attachments within the study in OnCore. 
5.1 Registration with the Masonic Cancer Center Clinical Trials Office 
Any patient who has been consented is to be registered in OnCore by the Primary Clinical 
Research Coordinator (PCRC) or designee. If a patient is consented, but not enrolled, the 
patient’s record is updated in OnCore as a screen failure and reason for exclusion 
recorded 

MT2018-06                                                          Phase II Trial of MGTA-456 for Hematologic Malignancies 
 
 
 
April 23, 2021 
Page 30 of 68 
CPRC #2018LS051 
5.2 .Study Enrollment with the Masonic Cancer Center Clinical Trials Office 
To be eligible for study enrollment, the patient must sign the treatment consent and meet 
each of the inclusion criteria and none of the exclusion on the eligibility checklist based on 
the eligibility assessment documented in the patient’s medical record. 
The Primary Clinical Research Coordinator (PCRC) or designee will assign the study 
treatment arm and add the on-treatment date to complete enrollment. 
5.3 Patients Who Are Enrolled But Do Not Receive Study Treatment 
If a patient is enrolled onto the study and is later found not able to begin the planned study 
treatment for whatever reason, the patient will be removed from study and treated at the 
physician’s discretion.  The study coordinator or designee will update OnCore of the 
patient’s non-treatment status and notify the Principal Investigator. The reason for removal 
from study prior to starting study treatment will be clearly indicated in OnCore.  The patient 
may be replaced. 
 
6 Treatment Plan 
In order to provide optimal patient care and to account for individual medical conditions, 
investigator discretion may be used in the prescribing of all supportive care drug therapy (i.e. 
acetaminophen, diphenhydramine, antimicrobials, etc.). 
 
All patients aged 3-55 years inclusive will receive the same conditioning and immunoprophylaxis 
for the prevention of acute and chronic GVHD, previously demonstrated to offer the best 
outcomes in recipients of partially HLA matched UCB.  Patients 0-3 years will receive a non-TBI 
containing conditioning regimen which is standard of care.  
 
TBI-Containing Regimen 
All patients aged 3-55 years will receive CY 120 mg/kg total dose, FLU 75 m/m2 total dose 
and TBI 1320 cGy total dose. Standard supportive care, including the use of G-CSF and 
prophylactic anti-bacterial, protozoal, viral and fungal agents, will also be prescribed.  
Supportive care will be modified throughout the transplant course at the treating physician’s 
judgement. 
Day 
Conditioning Regimen 
Immunoprophylaxis 
Hematopoietic Growth Factor 
-8 
FLU 25 mg/m2 IV over 1 hour 
(<10 kg: 0.83 mg/kg IV over 1 hour) 
 
-7 
FLU 25 mg/m2 IV over 1 hour 
(<10 kg: 0.83 mg/kg IV over 1 hour) 
CY 60 mg/kg IV over 2 hours 
 
-6 
FLU 25 mg/m2 IV over 1 hour 
(<10 kg: 0.83 mg/kg IV over 1 hour)  
CY 60 mg/kg IV over 2 hours 
 
-5 
Rest 
 

MT2018-06                                                          Phase II Trial of MGTA-456 for Hematologic Malignancies 
 
 
 
April 23, 2021 
Page 31 of 68 
CPRC #2018LS051 
Day 
Conditioning Regimen 
Immunoprophylaxis 
Hematopoietic Growth Factor 
-4 
TBI 165 cGy twice daily 
 
-3 
TBI 165 cGy twice daily 
Begin Tac / MMF (section 6.2) 
-2 
TBI 165 cGy twice daily 
 
-1 
TBI 165 cGy twice daily 
 
0 
MGTA-456 infusion 
 
+1 
 
Begin G-CSF 5 ug/kg/d until the absolute 
neutrophil count (ANC) is >2500/uL for 2 
consecutive days (section 6.4) 
 
Non-TBI-Containing Regimen 
For children <3 years of age will be conditioned with BU, FLU and MEL, as detailed below: 
Day 
Conditioning Regimen 
Immunoprophylaxis 
Hematopoietic Growth Factor 
-8 
BU IV once daily with dose based on PK 
calculator over 3 hours 
 
-7 
Bu IV once daily adjusted based on PK 
results over 3 hours 
 
-6 
Bu IV once daily adjusted based on PK 
results over 3 hours 
 
-5 
Bu IV once daily adjusted based on PK 
results over 3 hours 
 
-4 
FLU 25 mg/m2/day (0.83 mg/kg/day if < 10 
kg*) IV over 60 min 
MEL 50 mg/m2/day (1.7 mg/kg/day if < 10 
kg*) IV over 30 min 
 
-3 
FLU 25 mg/m2/day (0.83 mg/kg/day if < 10 
kg*) IV over 60 min 
MEL 50 mg/m2/day (1.7 mg/kg/day if < 10 
kg*) IV over 30 min 
Begin Tac / MMF (section 6.2) 
-2 
FLU 25 mg/m2/day (0.83 mg/kg/day if < 10 
kg*) IV over 60 min 
MEL 50 mg/m2/day (1.7 mg/kg/day if < 10 
kg*) IV over 30 min 
 
-1 
Rest 
 
 0 
MGTA-456 Infusion 
 
+1 
 
Begin G-CSF 5 ug/kg/d until the 
absolute neutrophil count (ANC) is 
>2500/uL for 2 consecutive days 
(section 6.4) 

MT2018-06                                                          Phase II Trial of MGTA-456 for Hematologic Malignancies 
 
 
 
April 23, 2021 
Page 32 of 68 
CPRC #2018LS051 
*Patients <11kg are currently ineligible because of the expected volume of DMSO in thawed 
products.  Once the washed product has been validated and approved by the FDA, patients <11 
kg may be eligible. 
6.1 Conditioning Regimen (day – 8 through day -1) 
Conditioning will be administered according to institutional guidelines.  Potential toxicities 
for each agent are detailed in section 7.1. 
 
6.1.1 TBI-Containing Regimen   
6.1.1.1 Fludarabine 
FLU will be administered at dose of 25 mg/m2 once a day as a 1 hour IV infusion 
on days -8, -7 and -6; total dose: 75 mg/m2. The dose is calculated based on actual 
body weight (ABW); however, if < 10 kg dosing will be 0.83 mg/kg/dose once a day 
as a 1 hour IV infusion). The dose will be adjusted if the GFR is ≤ 70.  There are no 
special precautions. 
6.1.1.2 Cyclophosphamide 
CY will be administered at a dose of 60mg/kg once a day as a 2 hour IV infusion 
on days -7 and -6; total dose: 120 mg/kg. The dose will be administered after a 
high volume fluid flush and mesna administration per institutional guidelines.  
Cyclophosphamide dosing is calculated based on actual weight (ABW) unless 
ABW >150% above Ideal Body Weight (IBW). Then the dose should be computed 
using adjusted body weight. The adjusted body weight = IBW + 0.5(ABW - IBW).  
For patients 1-18 years of age, the ideal body weight is calculated using the Traub 
and Johnson formulas: i.e,  <60 inches = ((height in cm)2 x 1.65)/1000;  >/= 60 
inches = 39 +[2.27 x (height in inches - 60)] for males and 42.2 + [2.27 x (height in 
inches – 60)] for females.  For patients >18 years of age, the ideal body weight is 
calculated using Devine's formula: i.e., 50 kg + (2.3 kg x (height in inches - 60)) for 
men; 45.5 kg + (2.3 kg x (height in inches - 60)) for women. 
6.1.1.3 
Total Body Irradiation 
TBI at a dose of 165 cGy will be administered twice a day on days -4, -3, -2 and -1; 
total dose 1320 cGy.  TBI administration procedure is described in Appendix II. 
6.1.2 Non-TBI-Containing Regimen   
6.1.2.1 Busulfan 
BU compounding, administration and monitoring should be performed per 
institutional guidelines and infused over 3 hours. The initial BU dose will be 
determined based on the weight of the patient upon admission and per our 
institutional BU standard of practice dose calculator. The first BU dose will be 
determined by a weight-based dosing nomogram. Refer to institutional guidelines 
for dosing of BU (Appendix III).   

MT2018-06                                                          Phase II Trial of MGTA-456 for Hematologic Malignancies 
 
 
 
April 23, 2021 
Page 33 of 68 
CPRC #2018LS051 
Seizure and VOD prophylaxis are prescribed according to institutional guidelines. 
Concomitant administration of azole anti-fungal agents (except fluconazole) and 
acetaminophen should be avoided within 72 hours before and after BU 
administration. 
6.1.2.2 Fludarabine 
FLU will be administered at dose of 25 mg/m2 once a day (<10 kg, dosing will be 
weight based: 0.83 mg/kg/day IV) as a 1 hour IV infusion on days -4, -3 and -2; 
total dose: 75 mg/m2. The dose is calculated based on ABW.  The dose will be 
adjusted if the GFR is ≤ 70.  There are no special precautions. 
6.1.2.3 
Melphalan 
MEL 50 mg/m2 IV will be administered over 30 minutes, 12 hours after FLU on 
days -4 to -2 (total of 150 mg/m2). For children <10 kg dosing will be weight based, 
with MEL 1.7 mg/kg (total of 5.1 mg/kg). Maintenance hydration of >1500 
ml/m2/day will be administered with MEL and for 24 hours following infusion.  
6.2 Immunoprophylaxis 
GVHD immunoprophylaxis will consist of Tacrolimus and MMF and will be administered 
according to institutional guidelines.  Potential toxicities for each agent are detailed in section 
7.2. 
6.2.1 Tacrolimus 
Tacrolimus will start day -3 and will be administered as a continuous IV infusion at 
a starting dose of 0.03 mg/kg/day.  Goal trough levels will be 10-15 ng/mL for the first 14 
days post-transplant and then decreased to a goal of 5-10 ng/ml thereafter. Tacrolimus 
dosing will be monitored and altered as clinically appropriate per institutional pharmacy 
guidelines.  Dose adjustments will be made on the basis of toxicity and/or tacrolimus levels 
outside of goal range.  Conversion from IV to oral tacrolimus will be done per 
institutional pharmacy guidelines as the patient tolerates and prior to discharge.  Potential 
toxicities are detailed in section 7.2. 
Patients will receive tacrolimus until day +100.  If no GVHD, the dose will be tapered 10% 
per week beginning on day 101, to discontinue at approximately day +180. 
In the presence of severe tacrolimus toxicities, other alternative agents may be used after 
review and approval by the co-PIs.  
6.2.2 Mycophenolate Mofetil 
MMF 3 gram/day IV/PO for adult patients divided in 2 or 3 doses. Pediatric patients will 
receive MMF at the dose of 15 mg/kg/dose (max 1 gram per dose) every 8 hours 
beginning day -3.  MMF dosing will be monitored and altered as clinically appropriate 
based on institutional guidelines.  Patients will be eligible for MMF dosing and 
pharmacokinetics studies. 

MT2018-06                                                          Phase II Trial of MGTA-456 for Hematologic Malignancies 
 
 
 
April 23, 2021 
Page 34 of 68 
CPRC #2018LS051 
Stop MMF at day +30 or 7 days after the ANC is >0.5 x 109 /L, whichever day is later.  
However, if there is acute GVHD, MMF should be continued for an additional 7 days after 
initiation of systemic therapy for acute GVHD.  Afterward, use of MMF is at the discretion 
of the attending physician. 
6.3 
MGTA-456 Infusion 
All cell products will be handled by the Cell Therapy Laboratory in the Molecular and 
Cellular Therapeutics (MCT) facility using validated standard operating procedures 
(SOPs).  The cell product will be released for human use to the inpatient unit after 
assessing the identity, sterility, purity and viability of the product.   
 
The target cell dose is >10 x 106 CD34/kg.  However, if the cell dose is < the target of 10 x 
106 CD34/kg, it may be infused as long as it exceeds 1 x 106 CD34/kg.  With regard to 
TNC, the maximum cell dose is 2.7 x 108/kg for children (<18 years) and 8.1 × 108 cells/kg 
for adults [expanded product only] based on the highest cell dose windows evaluated in 
prior studies. There is no lower limit for TNC dose, only a lower limit for CD34 dose. 
 
The infusion will be performed according to FACT accredited institutional policies.  The 
pre-medication and hydration regimen will be given following institutional guidelines (refer 
to section 6.4).  No steroids will be given prior to infusion. 
Under no circumstances will MGTA-456 (both the expanded product and its CD34 
negative fraction) be irradiated.  There must be no in-line leukocyte filter used with product 
infusion nor any medications or fluids infused in the same line with MGTA-456.  
Vital signs will be checked before and every 15 minutes during the infusion, at the 
completion of the infusion, and one hour post infusion per institutional guidelines.  More 
frequent vital signs may be required depending on reactions to the product infusion.  
Potential toxicities are detailed in section 7.3. 
The infusion will be around 30 minutes for all patients at a rate per institutional guidelines.    
Emergency drugs for hypersensitivity reactions should be available and administered 
according to institutional guidelines.  Oxygen with nasal prongs for standby use should be 
present in the room. 
Recipients of MGTA-456 will receive the associated CD34 negative fraction 1 hour after 
the infusion of the expanded product.  However, if the expanded product results in a 
reaction that necessitates intervention, the CD34 negative fraction infusion may be 
delayed but should be given within 24 hours after the infusion of the expanded product.   
6.4 Hematopoietic Growth Factor and Other Supportive Care 
All patients will receive G-CSF 5 mcg/kg/day IV (maximum dose 480 mcg) based on the 
actual body weight IV beginning on day +1 after MGTA-456 infusion.  G-CSF will be 
administered daily until the ANC is >2.5 x 109/L for two consecutive days and then 

MT2018-06                                                          Phase II Trial of MGTA-456 for Hematologic Malignancies 
 
 
 
April 23, 2021 
Page 35 of 68 
CPRC #2018LS051 
discontinued.  If the ANC decreases to <1.0 x 109/L, G-CSF should be reinstituted as 
needed to maintain an ANC >1.0 x 109/L.  Potential toxicities are detailed in section 7.2. 
Patients will receive transfusions, infection prophylaxis and nutritional support according to 
institutional guidelines. Infection prophylaxis should include, but is not limited to, agents or 
strategies (e.g., PCR screening and preemptive therapy) to prevent herpes simplex, 
cytomegalovirus (CMV), Pneumocystis carinii, and fungal infections. Transfusion 
thresholds for blood product are based on standard institutional guidelines. All blood 
products other than MGTA-456 will be irradiated. 
IVIG infusions (500 mg/kg/dose) is recommended for immunoprophylaxis for total serum 
IgG levels <400.  IgG levels will be monitored monthly for first 3 months and then as 
directed by the care team. 
6.5 Immunizations (Immune Reconstitution Sub-study) 
  To evaluate the pace of ‘functional’ immune recovery, Pediarix and Pneumovax will be 
administered at day 60, day 120, day 180 unless there is active acute or chronic GVHD.  
We will test for serologies for Hepatitis B, polio, pertussis, diphtheria, tetanus and 
pneumococcus pre-transplant, day 60, day 100, day 180 and one year post transplant. 
Other standard immunizations will be given at 12 months and two years unless there is 
active acute or chronic GVHD or other evidence of poor immunologic recovery.  
6.6 Duration of Study Participation 
Patients will be followed for 2 years after transplant. 
Follow-up after 2 years will be institutional standard of care follow up for all patients 
treated by HSCT at the institution.   
7 Expected Treatment Related Toxicities 
7.1 Potential Toxicities of the Conditioning Regimen 
 

MT2018-06                                                          Phase II Trial of MGTA-456 for Hematologic Malignancies 
 
 
 
April 23, 2021 
Page 36 of 68 
CPRC #2018LS051 
Cyclophosphamide 
Common 
Less Common 
Rare 
• low white blood cell count 
with increased risk of 
infection  
• hair loss or thinning, 
including face and body 
hair (usually grows back 
after treatment)  
• nausea  
• vomiting  
• loss of appetite  
• sores in mouth or on lips  
• bleeding from bladder, 
with blood in urine  
• diarrhea 
• long-term or short-term 
infertility in women and 
men 
• low platelet count 
(mild) with 
increased risk of 
bleeding  
• darkening of nail 
beds  
• acne  
• tiredness  
• infection 
• fetal changes if 
pregnancy occurs 
while taking 
cyclophosphamide  
 
• heart problems with high doses, with 
chest pain, shortness of breath, or 
swollen feet 
• severe allergic reactions 
• skin rash  
• scarring of bladder 
• kidney damage (renal tubular 
necrosis) which can lead to kidney 
failure 
• heart damage, with trouble getting 
your breath, swelling of feet, rapid 
weight gain 
• scarring of lung tissue, with cough 
and shortness of breath 
• second cancer, which can happen 
years after taking this drug 
• death from infection, bleeding, heart 
failure, allergic reaction, or other 
causes 
 
Busulfan 
Common 
Less Common 
Rare 
• Nausea/vomiting 
• Mucositis 
• Rash 
• Severe suppression of 
blood counts 
• Diarrhea 
• Fluid weight gain/edema 
• Alopecia 
• Hyperpigmentation 
• Veno-occlusive 
disease 
• Alveolar 
hemorrhage 
• Pulmonary fibrosis 
• Interstitial 
pneumonitis 
• Seizures (low frequency with anti-
seizure prophylaxis) 
• Hepatic fibrosis/liver failure 
 
 

MT2018-06                                                          Phase II Trial of MGTA-456 for Hematologic Malignancies 
 
 
 
April 23, 2021 
Page 37 of 68 
CPRC #2018LS051 
Fludarabine 
Common 
Less Common 
Rare 
• low white blood cell count 
with increased risk of 
infection  
• low platelet count with 
increased risk of bleeding  
• low red blood cell count 
(anemia) with tiredness 
and weakness 
• tiredness (fatigue)  
• nausea  
• vomiting  
• fever and chills 
• infection 
 
• pneumonia  
• diarrhea  
• loss of appetite 
• weakness 
• pain 
 
• numbness and tingling in hands 
and/or feet related to irritation of 
nerves  
• changes in vision  
• agitation  
• confusion 
• clumsiness 
• seizures 
• coma  
• cough  
• trouble breathing  
• intestinal bleeding 
• weakness  
• death due to effects on the brain, 
infection, bleeding, severe anemia, 
skin blistering, or other causes 
 
Melphalan 
Common 
Less Common 
Rare 
• Hypotension 
• Nausea and vomiting 
• Diarrhea 
• Hives/allergic reaction 
 
• Veno-occlusive 
disease 
 
• Dyspnea 
• Lung scarring 
 
 
Total Body Irradiation (TBI) 
Common 
Less Common 
Rare 
• nausea and vomiting 
• diarrhea 
• cataracts 
• sterility 
• endocrinopathies 
• growth failure 
• intestinal cramps 
• mucositis 
• parotitis 
• interstitial 
pneumonitis 
• generalized mild 
erythema 
• veno-occlusive 
disease 
• dysphagia 
• vertebral deformities 
• nephropathy 
• risk of 2nd malignancy years later 
(when given along with 
chemotherapy) 
 
 
 

MT2018-06                                                          Phase II Trial of MGTA-456 for Hematologic Malignancies 
 
 
 
April 23, 2021 
Page 38 of 68 
CPRC #2018LS051 
7.2 Potential Toxicities of GVHD Immunoprophylaxis and G-CSF 
 
GVHD Immunoprophylaxis  
Tacrolimus (Tac) 
Mycophenolate mofetil (MMF) 
• high blood pressure 
• abnormalities in blood chemicals 
• seizures 
• headaches 
• renal dysfunction to renal failure requiring 
dialysis 
 
• nausea and vomiting 
• diarrhea 
• constipation 
• lowering of blood counts 
• leg cramps 
• skin rash 
• difficulty sleeping 
• chemical 
imbalances 
including 
high 
blood sugar 
• headaches 
• dizziness 
• high blood pressure 
 
G-CSF Hematopoietic Growth Factor 
• bone pain 
• headaches 
• body aches 
• fatigue 
 
• nausea/vomiting 
• insomnia 
• dyspnea 
• rash 
• edema 
7.3 Potential Side effects of Immunizations 
Pediarix 
• injection site reactions 
• fever 
• joint pain 
• body aches, 
• loss of appetite 
• nausea 
• vomiting 
• diarrhea 
 
Pneumovax 
• injection site reactions  
• muscle or joint aches or pain 
• fever 
• chills 
• headache 
• nausea 
• vomiting 

MT2018-06                                                          Phase II Trial of MGTA-456 for Hematologic Malignancies 
 
 
 
April 23, 2021 
Page 39 of 68 
CPRC #2018LS051 
• stiffness of the arm or the leg where the vaccine was injected 
• weakness 
• fatigue 
• skin rash 
 
7.4 Potential Adverse Events (AE) associated with the Infusion of Cryopreserved 
HSPC Products (including MGTA-456) 
 
Cryopreserved HSPC Products / MGTA-456 
Infusional Toxicities within 48 Hours 
• nausea and vomiting  
• possible allergic reaction (including itching, hives, flushing [red face], shortness of breath, 
wheezing, chest tightness, skin rash, fever, chills, stiff muscles, or trouble breathing) 
• acute hemolytic reactions in setting of ABO incompatibility 
• febrile nonhemolytic reactions 
• anaphylactoid or anaphylactic reactions 
• transfusion-related acute lung injury (TRALI) 
• DMSO toxicities (eg headache, hypertension, cardiac toxicity, nausea and vomiting) 
• transmission of occult bacterial, viral or protozoal infections 
• transfusion-associated circulatory overload (TACO) 
• hypothermia 
• non-immunologic hemolysis 
Later AEs after the Initial 48 Hours 
• Failure to engraft 
• GVHD – acute and chronic 
• Slow immune recovery and high risks of opportunistic infection 
• Diminished graft-versus-leukemia effect and greater risk of relapse 
 
7.5 Recommended Treatment of Adverse Events 
The clinical management of the complications discussed below will be per institutional 
guidelines. The following text is considered general guidance only. 
7.5.1 Slow Engraftment/Graft Failure 
The clinical management of slow engraftment/graft failure will be per institutional 
guidelines. Management of slow engraftment is triggered by the assessment of peripheral 
blood and bone marrow on Day 21. If at Day 21, the ANC is ≤0.5 × 109/L and bone 
marrow cellularity is ≤5%, G-CSF dose may be doubled or granulocyte macrophage-
colony stimulating factor (GM-CSF) may be added at 250 mcg/m2/d, the availability of the 
back-up UCB unit(s) that was put on hold at the time of patient enrolment is confirmed and 
a Day 28 bone marrow biopsy is scheduled. 

MT2018-06                                                          Phase II Trial of MGTA-456 for Hematologic Malignancies 
 
 
 
April 23, 2021 
Page 40 of 68 
CPRC #2018LS051 
If on Day 28 ANC remains ≤0.5 × 109/L and bone marrow cellularity is ≤5%, consideration 
will be given to performing a second HSC infusion using the previously identified back up 
source after some form of preconditioning per institutional standard of care.  
7.5.2 Anemia 
Transfusions of packed red blood cells are indicated for symptomatic management of 
anemia. An attempt should be made to maintain the hematocrit >24% and hemoglobin >8 
g/dL. Irradiated (1500 to 3000 cGy) blood products will be used in accordance with the 
institutional standard of care. 
7.5.3 Thrombocytopenia 
Prophylactic platelet transfusions should be given to maintain the platelet count >10 × 
109/L or above the level at which signs of bleeding are known to occur, whichever is 
greater. All aspirin containing drugs are to be avoided. The patients should receive no 
intramuscular injections while thrombocytopenic. Irradiated (1500 to 3000 cGy) blood 
products will be used in accordance with the institutional standard of care. 
7.5.4 Nutrition 
All patients will be candidates for total parenteral nutrition; length of use is per institutional 
guidelines. 
7.5.5 Acute GVHD 
Patients will be considered evaluable for acute GVHD unless they are known to have 
autologous recovery or die before Day 21 without GVHD. Organ involvement will be 
staged using the criteria outlined in the Appendix IV. Biopsy of each organ site at 
diagnosis or major change in disease activity will be performed unless clinical 
circumstances make it impossible. 
7.5.6 Infusional Reaction 
MGTA-456 expanded cell product, like other blood products, may cause infusional 
reactions, including hemodynamic effects or acute hypersensitivity. Furthermore, the co-
infusion of residual components of the expansion culture carries theoretical attendant 
risks. These time-limited events are expected to occur within the first 24 hours [38, 39], 
and may range from mild to moderate in severity and may include gastrointestinal 
(nausea, vomiting, diarrhea and abdominal cramps), respiratory (cough, dyspnea), 
cardiovascular (hypotension, hypertension, bradycardia), neurological, or dermatological 
(skin flushing, rash) events, infection, and anaphylaxis [40].  
Emergency drugs should be available and administered per institutional guidelines. 
Oxygen with nasal prongs for standby use should be present in the room. 

MT2018-06                                                          Phase II Trial of MGTA-456 for Hematologic Malignancies 
 
 
 
April 23, 2021 
Page 41 of 68 
CPRC #2018LS051 
7.5.7 Engraftment Syndrome/Transfusion Related Acute Lung Injury (TRALI) 
Engraftment syndrome is a syndrome characterized by fever, fluid retention, rash and 
pulmonary infiltrates proximal to the time of neutrophil recovery after high dose 
conditioning and HSCT, likely mediated by activated leukocytes and proinflammatory 
cytokines. Treatment is supportive, including antipyretics, oxygen and diuretics, and 
systemic corticosteroids or therapies directed to specific proinflammatory cytokines (eg, 
IL6). 
TRALI is a rare but serious syndrome characterized by sudden acute respiratory distress 
following transfusion. It is defined as new, acute lung injury during or within six hours after 
blood product administration in the absence of other risk factors for acute lung injury.  
TRALI is thought to be caused by activation of recipient neutrophils by donor-derived 
antibodies targeting HLA or human neutrophil antigen, in most cases. Non-antibody-
mediated cases occur and may be mediated by biologic response modifiers present in the 
transfused blood product, along with recipient factors. Treatment is supportive and 
consists of oxygen, ventilator support and management of fluid balance. 
8 
Schedule of Patient Activities 
Scheduled evaluations after screening and until engraftment may be performed +/-3 days from 
the targeted date; assessments performed after engraftment and through day 100 may be 
done +/-7 days of the targeted date.  After day 100 assessments may be done +/- 30 days of 
the targeted date.  In addition, targeted days may be altered as clinically appropriate (e.g., 
intercurrent illness, maximum blood volume for clinical care preventing research lab testing, 
patient refusal).     

MT2018-06                                                          Phase II Trial of MGTA-456 for Hematologic Malignancies 
 
 
 
April 23, 2021 
Page 42 of 68 
CPRC #2018LS051 
Schedule of Assessments – Standard of Care 
Study Phase 
Screening 
Conditioning
24 
MGTA-
456 
Follow up 
Study Day(s) 
-60 to -10 
-8 to -1 
0 
7 
±3 
14 
±3 
21 
±3 
28 
±3 
35 
±3 
42 
±3 
60 
±3 
100 
±10 
180 
±30 
360±30 
and 
720±30 
Informed 
Consent 
X 
SCRF 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnancy test1 
X 
SCRF 
 
 
 
 
 
 
 
 
 
 
 
X          
(at 360 
only) 
Medical 
history/current 
medical 
conditions 
OCRF 
At every visit with a medical provider 
Concomitant 
therapies 
Reviewed at every visit with a medical provider 
Body height 
X 
SCRF 
 
 
 
 
 
 
 
 
 
 
 
 
Vital signs2 
X 
SCRF 
 
X 
ICRF 
 
 
 
 
 
 
 
 
 
 
Physical               
examination 
X 
OCRF  
At every visit with a medical provider 
Karnofsky / 
Lansky 
Performance 
status 
X 
SCRF 
 
 
 
 
 
 
 
 
X 
OCRF  
X 
OCRF 
X 
OCRF 
X 
OCRF 
Echocardiogra
m ECHO or 
MUGA 
X 
SCRF 
 
 
 
 
 
 
 
 
 
 
 
X 
OCRF 
 Adults: chest x-
ray/ chest CT 
Peds: chest CT 
X 
SCRF 
 
 
 
 
 
 
 
 
 
 
 
 
PFT (if capable) 
otherwise S02 
X 
SCRF 
 
 
 
 
 
 
 
 
 
 
 
X 
OCRF 
GFR or 
creatinine 
clearance 
X 
SCRF 
 
 
 
 
 
 
 
 
 
 
 
 
Hematology3 
X 
SCRF 
X 
Daily 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
Blood 
chemistries 
X 
SCRF 
 
X 
 
 
 
 
 
 
 
 
 
 

MT2018-06                                                          Phase II Trial of MGTA-456 for Hematologic Malignancies 
 
 
 
April 23, 2021 
Page 43 of 68 
CPRC #2018LS051 
Study Phase 
Screening 
Conditioning
24 
MGTA-
456 
Follow up 
Study Day(s) 
-60 to -10 
-8 to -1 
0 
7 
±3 
14 
±3 
21 
±3 
28 
±3 
35 
±3 
42 
±3 
60 
±3 
100 
±10 
180 
±30 
360±30 
and 
720±30 
Immunoglobulin 
levels 
X 
OCRF 
 
 
 
 
 
X 
OCRF 
 
 
X 
OCRF 
X 
OCRF 
X 
OCRF 
X 
OCRF 
Viral screen4 
X 
SCRF 
 
 
 
 
 
 
 
 
 
 
 
 
CMV and EBV 
surveillance  
X 
SCRF 
 
 
X 
OCRF 
X 
OCRF 
X 
OCRF 
X 
OCRF 
X 
OCRF 
X 
OCRF 
X 
OCRF 
X 
OCRF 
 
 
HHV6 
surveillance 
(pcr) 
X 
SCRF 
 
 
X 
OCRF 
X 
OCRF 
X 
OCRF 
X 
OCRF 
X 
OCRF 
X 
OCRF 
 
 
 
 
Anti-HLA 
antibody 
X 
SCRF 
 
 
 
 
 
 
 
 
 
 
 
 
GVHD score5 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
OCRF 
X 
OCRF 
X 
OCRF 
Adverse 
events6 
 
SAEs only 
X 
Disease Status 
Assessments 
X 
SCRF 
 
 
 
 
 
 
 
 
 
X 
OCRF 
X 
OCRF 
X 
OCRF 
Chimerism7 
(CD3, 
CD33/66) 
 
 
 
 
 
X 
OCRF 
 
 
 
X 
OCRF 
X 
OCRF 
X 
OCRF 
X 
OCRF 
T-cell subsets 
 
 
 
 
 
 
X 
OCRF 
 
 
X 
OCRF 
X 
OCRF 
X 
OCRF 
X 
OCRF 
 
Abbreviations: LTFU=long term follow-up; ECHO=echocardiogram; MUGA=multigated acquisition; PFT=pulmonary function tests; GFR=glomerular filtration rate; 
CMV=cytomegalovirus;HHV6=human herpes virus 6; GVHD=graft-versus-host disease; SAE=severe adverse event; SCRF=result recorded in a screening case 
report form; OCRF=result recorded in outcomes case report form; ICRF=result recorded in infusion case report form; x=result retained in electronic medical record 
with specific results eg days to ANC and platelet recovery, retained in the BMT database.  Dates of transfusions, resource utilization and costs will be obtained 
from the electronic medical record and Fairview Health System after day 100 with summary files maintained in the BMT database.  
 
1 For females of child bearing potential (post-menarche), serum pregnancy testing is required at screening and 1 year visits. If not done within 7 days of Day -9, 
pregnancy test must be repeated prior to initiating conditioning. 
2 Vital signs include body weight, body temperature, blood pressure, pulse, and pulse oximetry. Vital signs will be checked before and every 15 minutes during the 
infusion, at the completion of the infusion, and one hour post infusion per institutional guidelines.  More frequent vital signs may be required depending on 
reactions to the product infusion.   Weight will be collected at pre-infusion only. The highest temperature recorded within 24 hr period will be reported. 
3 Hematology will need to be repeated daily during inpatient hospitalization, then at every scheduled visit. The patient will remain hospitalized until neutrophil 
engraftment is achieved. 
4 All patients will be screened for hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), hepatitis C virus (HCV), herpes simplex virus (HSV), 
cytomegalovirus, (CMV), Epstein-Barr virus (EBV), and human T cell lymphotropic virus 1/2 (HTLV1/2). After Screening, infection surveillance will include human 
herpesvirus 6 (HHV-6) (to be tested weekly through Day 42), and CMV and EBV (to be tested weekly through Day 100). 

MT2018-06                                                          Phase II Trial of MGTA-456 for Hematologic Malignancies 
 
 
 
April 23, 2021 
Page 44 of 68 
CPRC #2018LS051 
5 Weekly assessments for GVHD is collected starting at Day 7 until hospital discharge, and then at every scheduled visit. aGVHD will be collected until Day 100 
and cGVHD will be collected starting at Day 100 and then at Day 180 and 360/EOS 
6 AEs must be reported starting from the day of transplant Day 0 and per the timeline specified in Section 9. SAEs will be collected from the time conditioning is 
initiated at Day -9 and per the timeframe specified in Section 9. 
7 Chimerism will be assessed by sorting for 4 subsets - CD3 T cells, CD33/66 myeloid cells, CD19 B cells and CD56 NK cells.  Evaluation of CD3 and CD33/66 
subsets is considered SOC assessments on days 21, 28, 35, 42, 60, 100, 180, 360 and 720. Blood volume limits will be monitored for all patients; if the blood 
volume for SOC blood work exceeds the maximum allowable, research blood samples will either be cancelled or delayed until a date and time it is considered 
appropriate based on institutional criteria.  
 

MT2018-06                                                          Phase II Trial of MGTA-456 for Hematologic Malignancies 
 
 
 
April 23, 2021 
Page 45 of 68 
CPRC #2018LS051 
Schedule of Assessments – Research Only   
Study Phase 
Screening 
Conditioning 
MGTA-
456 
Follow up 
Study Day(s) 
-60 to -10 
-8 to -1 
0 
7 
±3 
14 
±3 
21 
±3 
28 
±3 
35 
±3 
42 
±3 
60 
±3 
100 
±10 
1206 
±10 
 
180 
±30 
360±30 
and 
720±30 
MGTA-456 
Infusion1,2  
 
 
X 
OCRF 
 
 
 
 
 
 
 
 
 
 
 
Chimerism3, 8 
(CD19/20) 
(CD16/56) 
 
 
 
X 
OCRF 
X 
OCRF 
X 
OCRF 
X 
OCRF 
 
 
X 
OCRF 
X 
OCRF 
 
X 
OCRF 
X 
OCRF 
Chimerism3, 8 
(CD3, CD33/66) 
 
 
 
X 
OCRF 
X 
OCRF 
 
X 
OCRF 
X 
OCRF 
X 
OCRF 
 
 
 
 
 
Cellular immune 
reconstitution4 
X 
OCRF 
 
 
 
 
 
X 
OCRF 
 
X 
OCRF 
X 
OCRF 
X 
OCRF 
 
X 
OCRF 
X 
OCRF 
T cell repertoire4 
X 
OCRF3 
 
 
 
 
 
X 
OCRF 
 
X 
OCRF 
X 
OCRF 
X 
OCRF 
 
X 
OCRF 
X 
OCRF 
TREC5 
 
 
 
 
 
 
X 
OCRF 
 
X 
OCRF 
X 
OCRF 
X 
OCRF 
 
X 
OCRF 
X 
OCRF 
Serologies: Hep B, 
polio, pertussis, 
diphtheria,  
tetanus, 
pneumococcal 
X 
OCRF 
 
 
 
 
 
 
 
 
X 
OCRF 
X 
OCRF 
 
X 
OCRF 
X 
Pediarix and 
Pneumovax 
vaccines9 
 
 
 
 
 
 
 
 
 
X  
OCRF 
 
X  
OCRF 
X  
OCRF 
 
 
Abbreviations: OCRF=result recorded in outcomes case report form 
 
1 Two therapeutic cell preparations will be infused sequentially in the following order. First= a target cell dose is >10 x 106 CD34/kg.  However, if the cell dose is < 
the target of 10 x 106 CD34/kg, it may be infused as long as it exceeds 1x106 CD34+/kg BW cells will be administered.  With regard to TNC, the maximum cell 
dose is 2.7 x 108/kg for children (<18 years) and 8.1 × 108 cells/kg for adults [expanded product only] based on the highest cell dose windows evaluated in prior 
studies. There is no lower limit for TNC dose, only a lower limit for CD34 dose.. The exact dose level achieved after stem cell expansion should be recorded. 
Second = CD34- negative fraction from the same UCB unit. All available CD34-negative cells will be administered. 

MT2018-06                                                          Phase II Trial of MGTA-456 for Hematologic Malignancies 
 
 
 
April 23, 2021 
Page 46 of 68 
CPRC #2018LS051 
2.Graft Evaluation.  The total number of CD3+ and CD34+ cells and methylcellulose colony-forming cells will be enumerated for all UCB grafts beinfused into the 
patient regardless prior processing (standard of care).  Proportions of CD34+CD133+CD90+ cells and T cell subsets will also be determined (research). 
3.Chimerism will be assessed by sorting for 4 subsets - CD3 T cells, CD33/66 myeloid cells, CD19 B cells and CD56 NK cells.  Evaluation of CD19 and CD56 is 
research at all time points; evaluation of CD3 and CD33/66 subsets is research on days 7 and 14 but not for other time points, as this would be considered SOC 
assessments on days 21, 28, 35, 42, 60, 100, 180, 360 and 720. Blood volume limits will be monitored for all patients; if the blood volume for SOC blood work 
exceeds the maximum allowable, research blood samples will either be cancelled or delayed until a date and time it is considered appropriate based on 
institutional criteria.  
4 Immune Reconstitution. Patients will also have an extensive evaluation of immune reconstitution, including NK and B cell subset but particular emphasis on T 
cell subsets, ie TCR rearrangement excision circles (TREC) and naïve (CD45RA+/CD27+), central memory (CD45RA+CD27-), effector memory (CD45RA-
CD27-) and stem/memory (Tsm, CD8/45RA/62L/95/CCR7+) populations, as well as TCR repertoire diversity. In addition, Quantitative recovery of 
immunoglobulin synthesis and functional T and B cell generation and antigen driven responses in response to immunizations will be evaluated.  For adult 
patients, six 10 mL green heparin tubes and one 10 mL red top tube at each time point. For pediatric patients, two 10 mL green heparin tubes and one 5 mL red 
top tube (not to exceed 2 mL/kg in patients ≤ 40kg ) per time point 
5 Frozen cells (no extra blood) 
6 At subject’s home clinic/provider 
7  Diphtheria and tetanus ab panel(lab 792) 0.8 ml-2 ml red top; polio antibody  (lab 653) 0.6 ml-2.0 ml red top; hepatitis B surface antibody (lab 6383) 1.2 ml-2 ml 
red top; B. pertussis lab 6759 0.8-2 ml red top; pneumo 7 (lab 5896) 0.7-3 ml red top.  
8 If at any time point WBC < 500, do not draw sample for chimerism 
9 Unless there is active acute or chronic GVHD. Missed immunizations will not be considered study deviations.

MT2018-06                                                          Phase II Trial of MGTA-456 for Hematologic Malignancies 
 
 
 
April 23, 2021 
Page 47 of 68 
CPRC #2018LS051 
9 Adverse Event Monitoring, Recording and Reporting 
Toxicity and adverse events will be classified according to NCI's Common Terminology 
Criteria for Adverse Events V 5.0 (CTCAE) and reported on the schedule below. A copy of the 
CTCAE events can be downloaded from 
http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm#ctc_50  
9.1 Definitions 
The following definitions are based on the Code of Federal Regulations Title 21 Part 312.32 
(21CFR312.32(a)). 
Adverse Event:  Any untoward medical occurrence associated with the use of a drug in 
humans, whether or not considered drug related.  
Suspected Adverse Reaction:  Any adverse event for which there is a reasonable possibility 
that the drug caused the adverse event.  
Treatment-Emergent Adverse Event:  Any event not present prior to the initiation of the 
treatment or any event already present that worsens in either intensity or frequency following 
exposure to the treatment.  A treatment emergent AE refers to an event temporally related to 
the study treatment regardless of the causality assessment by the investigator. 
Life-Threatening Adverse Event Or Life-Threatening Suspected Adverse Reaction: An 
adverse event or suspected adverse reaction is considered “life-threatening” if, in the view of 
either the investigator or sponsor, its occurrence places the patient or subject at immediate 
risk of death.  Note:  a life-threatening event does not necessarily equate to a CTCAE grade 4. 
Serious Adverse Event Or Serious Suspected Adverse Reaction:  An adverse event or 
suspected adverse reaction is considered “serious” if, in the view of either the investigator or 
sponsor, it results in any of the following outcomes:  
• 
Death 
• 
A life-threatening adverse event 
• 
Inpatient hospitalization or prolongation of existing hospitalization 
• 
A persistent or significant incapacity or substantial disruption of the ability to 
conduct normal life functions 
• 
A congenital anomaly/birth defect.  
 
Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered serious when, based upon appropriate medical judgment, 
they may jeopardize the patient or subject and may require medical or surgical intervention to 
prevent one of the outcomes listed in this definition.  
Unexpected adverse event or unexpected suspected adverse reaction: An adverse event 
or suspected adverse reaction is considered "unexpected" if it is not listed in the investigator 
brochure or is not listed at the specificity or severity that has been observed; or, if an 
investigator brochure is not required or available, is not consistent with the risk information 
described in the general investigational plan or elsewhere in the current application, as 

MT2018-06                                                          Phase II Trial of MGTA-456 for Hematologic Malignancies 
 
 
 
April 23, 2021 
Page 48 of 68 
CPRC #2018LS051 
amended.  Thus, as defined by the FDA adverse events that occur as part of the disease 
process or underlying medical conditions are considered unexpected; however, for the 
purposes of this study they will not be documented or reported. 
9.2 Adverse Event Monitoring, Recording and Reporting 
9.2.1 Event Monitoring  
Monitoring for adverse events will begin with MGTA infusion and continue through 2 year 
post-transplant anniversary visit.    
9.2.2 Event Recording/Documentation 
Due to the intentional use of chemotherapy and radiation to eliminate residual leukemia 
and provide adequate immune suppression to reduce the risk of graft rejection, numerous 
toxicities are anticipated in this patient population as detailed in section 7.  Therefore, 
adverse event documentation in OnCore for the purposes of this study will focus on: 
• 
All grade 4 or 5 non-hematologic adverse events through neutrophil 
engraftment or Day 42, whichever is shorter 
• 
All serious unexpected suspected adverse reactions after Day 42 (or 
engraftment) through 2 years post-transplant upon knowledge  
• 
Targeted toxicities (appendix V) for all patients at the following time points: 
o Prior to the MGTA infusion 
o 4 hours (+/- 1 hour) post UCB infusion  
o 24 hours (+/- 1 hour) post UCB infusion 
o 48 hours (+/- 1 hour) post UCB infusion 
Transplant related outcomes will be collected as routine by the BMT Database. 
9.2.3 Event Reporting to the IRB, FDA and Cancer Center 
Certain events will require prompt reporting according to the table below: 
Agency 
Criteria for reporting 
Timeframe 
Form to 
Use 
Submission 
information 
Copy to: 
IRB 
 
Events requiring prompt reporting 
including, but not limited to 
unanticipated death of a locally enrolled 
subject(s); new or increased risk; any 
adverse event  that require a change to 
the protocol or consent form or any 
protocol deviation that resulting in harm 
refer to  
http://www.research.umn.edu/irb/forms.
html 
within 5 
business 
days of 
discovery 
Report 
Form 
irb@ 
umn.edu 
SAE 
Coordinator 
mcc-
saes@umn.
edu 
Masonic Cancer
Center 
SAE 
Coordinator 
Events that meet the definition of dose 
limiting toxicity or an early study stopping 
rule 
At time of 
reporting 
Event Form 
mccsaes@u
mn.edu 

MT2018-06                                                          Phase II Trial of MGTA-456 for Hematologic Malignancies 
 
 
 
April 23, 2021 
Page 49 of 68 
CPRC #2018LS051 
 
At the time of continuing review/IND annual report, relevant events recorded in OnCore 
will be reported in summary format by those persons responsible for such reporting.  
9.3 Monitoring for Stopping Rule Events 
In addition to the event monitoring and reporting described in the previous section, the 
following events will be considered excess toxicity and be reported using the Event Form 
found in OnCore: 
• 
Excess graft failure at day 42 
• 
Excess TRM at day 100 
• 
Excess grade III-IV acute GVHD 
A copy of the completed Event Form must be sent to the SAE Coordinator (mcc-
saes@umn.edu) at the time it is submitted to the study statistician.   
As these events are outcomes of the treatment, not toxicity as found in CTCAE, they should 
only be recorded/reported as an AE, if they meet the criteria found in section 9.2      
10 Study Data Collection and Monitoring 
10.1 Data Management 
This study will collect regulatory and clinical data using University of Minnesota CTSI’s 
instance of OnCore® (Online Enterprise Research Management Environment). 
The Oncore database resides on dedicated secure and PHI compliant hardware 
consisting of 3 physical servers: dev, DR, and production. The dev server is located in 
the University of Minnesota (UMN) datacenter (WBOB) and houses six database 
FDA 
 
 
Unexpected  fatal or unexpected life 
threatening suspected adverse reaction 
 
 
As soon as 
possible but 
no later than 
7 calendar-
days 
Institution
al SAE 
form  
Submit as an 
amendment 
to IND 
 
1) Serious and unexpected suspected 
adverse reaction or 
2)  increased occurrence of serious 
suspected adverse reactions over that 
listed in the protocol or investigator 
brochure or 
3) findings from other sources (other 
studies, animal or in vitro testing) 
As soon as 
possible but 
no later than 
15 calendar-
days 
Note:  Events due to the disease under treatment or an preexisting medical condition will not 
require expedited reporting to the FDA for the purposes of this study 
Magenta 
1)  Product manufacturing failures 
2)  Failure of hematopoietic engraftment 

MT2018-06                                                          Phase II Trial of MGTA-456 for Hematologic Malignancies 
 
 
 
April 23, 2021 
Page 50 of 68 
CPRC #2018LS051 
instances (test, train, sandbox, mcc reports, oncdm, and vendor) that are backed up 
locally because the data is refreshed from Oncore production data. The production 
server is located in the UMN datacenter (WBOB). All the data servers are managed by 
the Academic Health Center – Information Systems (AHC-IS) virtual servers which utilize 
clustered infrastructure to provide real-time failover of virtual servers. This real-time 
clustering is physically limited to the UMN data center. All relevant AHC IS procedures 
related for PHI compliant servers (as required by the Center of Excellence for HIPAA 
Data) apply to Oncore databases. 
The integrated data will be stored in PHI compliant servers managed by AHC IS with 
access given to those authorized users in the Clinical and Translation Science Institute 
Informatics team (CTSI BPIC and MCC CISS). The data will be integrated and extracted 
to researchers through the CTSI Informatics team and will be delivered through secure 
and compliant mechanisms (e.g. AHC IE data shelter, BOX, sftp, etc). If data de-
identification is needed, then compliant AHC IE data de-identification tools will be used. 
The informatics team will grant the IRB approved study team members access to data. 
Additional data about correlative laboratory samples generated by the Masonic Cancer 
Center Translational Therapy Laboratory (TTL) from the protocol-directed correlative 
research samples is stored in their Laboratory Information Management System 
(LIMS).The LIMS database application is also stored on a production server located in 
the UMN datacenter (WBOB) and is managed by the Academic Health Center 
Key study personnel are trained on the use of OnCore and will comply with protocol 
specific instructions embedded within the OnCore. 
10.2 Case Report Forms 
Participant data will be collected using protocol specific CRFs developed within OnCore, 
based on its library of standardized forms.  The CRFs will be approved by the study’s 
Principal Investigator and the Biostatistician prior to release for use.  There is a 
screening case report form (SCRF) which the Study Coordinator or designee will use to 
register the patient into OnCore at time of study entry.  An infusion case report form 
(ICRF) will be used to document adverse events during the infusion of MGTA-456 
(expanded product and CD34 depleted product) and outcomes case report form (OCRF) 
will record specific outcomes data for submission to the BMT Database.  As 
medications, blood product administration, provider examinations and 
laboratory/radiographic data are accessible to the BMT Database through a Data 
Sharing Agreement, CRFs will only be needed for specific data collection.   
10.3 Data and Safety Monitoring Plan 
The study’s Data and Safety Monitoring Plan will be in compliance with the University of 
Minnesota Masonic Cancer Center's Data & Safety Monitoring Plan (DSMP), which can 
be accessed at http://z.umn.edu/dmsp  
For the purposes of data and safety monitoring, this study is classified as high risk 
(under a locally held IND).  Therefore the following requirements will be fulfilled: 

MT2018-06                                                          Phase II Trial of MGTA-456 for Hematologic Malignancies 
 
 
 
April 23, 2021 
Page 51 of 68 
CPRC #2018LS051 
 The Masonic Cancer Center Data and Safety Monitoring Council (DSMC) will review 
the study’s progress at least quarterly with the understanding the Cancer Protocol 
Review Committee (CPRC) may require more frequent reporting. 
 The PI will comply with at least twice yearly monitoring of the project by the Masonic 
Cancer Center monitoring services. 
 The PI will oversee the submission of all reportable adverse events per the definition 
of reportable in section 9.2.3 to the Masonic Cancer Center’s SAE Coordinator, the 
University of Minnesota IRB, and the FDA.   
 
In addition, at the time of the continuing review with the University of Minnesota IRB, a 
copy of the report with any attachments will be submitted to the CPRC. 
10.4 IND Annual Reports 
In accordance with regulation 21 CFR § 312.33, the sponsor-investigator with assistance 
from the MCC Clinical Trials Office (CTO) will submit a progress report annually.  The 
report will be submitted within 60 days of the anniversary date that the IND went into 
effect.    
10.5 Data Sharing with Magenta 
Only data related to MGTA-456 product manufacturing data and product failures (lot 
release, failure to engraft) will be shared with Magenta.   
10.6 Monitoring 
The investigator will permit study-related monitoring, audits, and inspections by the IRB, 
government regulatory bodies, and University of Minnesota compliance groups.  The 
investigator will make available all study related documents (e.g. source documents, 
regulatory documents, data collection instruments, study data, etc.).  The investigator will 
ensure the capability for inspections of applicable study-related facilities (e.g. pharmacy, 
diagnostic laboratory, etc.) will be available for trial related monitoring, audits, or regulatory 
inspections. 
10.7 Study Record Retention 
The investigator will retain study records including source data, copies of case report form, 
consent forms, HIPAA authorizations, and all study correspondence in a secured facility 
for at 6 years after the study file is closed with the IRB and FDA.   
In addition, the CTO will keep a master log of all patients participating in the study with 
sufficient information to allow retrieval of the medical records for that patient.  
Please contact the CTO before destroying any study related records. 
 
 

MT2018-06                                                          Phase II Trial of MGTA-456 for Hematologic Malignancies 
 
 
 
April 23, 2021 
Page 52 of 68 
CPRC #2018LS051 
11 Definition of Study Endpoints 
11.1 Neutrophil Recovery 
All patients will have daily complete blood counts beginning on day +1 with white blood 
cell differential assessments beginning when the total WBC ≥0.5 x 109/L. The day of 
neutrophil recovery will be the first of three consecutive days when the ANC is ≥0.5 x 
109/L. 
11.2 Platelet Recovery 
The frequency of platelet count assessments will vary over the course of the transplant 
period. During the firsts 100 days after transplant, all patients will have at least weekly 
platelet counts. The day of platelet recovery will be the first of three consecutive 
measurements when the platelet count is ≥20,000 x 109/L without a platelet transfusion in 
the prior 7 days. 
11.3 Engraftment 
Engraftment is determined by neutrophil recovery with hematopoietic cells of donor origin 
(chimerism).  Complete chimerism is defined as 90-100% of marrow cells or CD33/66+ 
peripheral blood cells of donor origin.  Partial chimerism is defined as 10-90% donor cells 
and autologous recovery is defined as 0-10% donor cells. 
11.4 Graft Failure 
Graft failure is the absence of neutrophil recovery or lack of chimerism from any etiology.   
• Primary Graft Failure is defined by the absence of neutrophil recovery by day 42 after 
UCBT or absence of chimerism before day 42.  Note: Patients surviving ≥14 days will 
be considered evaluable and patients receiving a ‘back-up’ unmanipulated graft within 
5 days of the transplant, as a result of bioassays outside the specification limits for 
MGTA-456, will not be considered evaluable 
• Secondary Graft Failure is defined by a recurrence of neutropenia (ANC <0.5 x 109/L 
lasting >7 days) or autologous recovery after prior engraftment. 
11.5 Graft-versus-Host Disease 
GVHD is the immune response of donor cells directed against host tissues.  There are two 
distinct forms – acute and chronic. 
• 
Acute GVHD is syndrome that typically occurs in the first 100 days after transplant 
and is characterized by abdominal pain or cramps, nausea, vomiting, and diarrhea, 
jaundice or other liver function abnormalities, and skin rash.  The diagnosis is based 
on the presence of one or more of these symptoms without other etiology and often 
supported by tissue biopsy.  Patients will be assigned an overall GVHD score based 
on extent of skin rash, volume of diarrhea and maximum bilirubin level.  At day 100, 
the maximum severity will be determined using the NIH Consensus Criteria. 
• 
Chronic GVHD is a syndrome that typically occurs 3 months or more after transplant 
and is characterized by dry eyes or vision changes, dry mouth with increased 
sensitivity to foods, fatigue, muscle weakness, arthralgias, arthritis, contractures, skin 

MT2018-06                                                          Phase II Trial of MGTA-456 for Hematologic Malignancies 
 
 
 
April 23, 2021 
Page 53 of 68 
CPRC #2018LS051 
rash, hyper and hypopigmentation, scleroderma, obliterative bronchiolitis, steatorrhea, 
weight loss.  The diagnosis is based on the presence of one or more of these 
symptoms without other etiology and often supported by tissue biopsy. 
11.6 Transplant-Related Mortality  
TRM is a death in continuous complete remission.  
11.7 Relapse  
Relapse is the recurrence of the underlying disease for which the transplant was 
performed.  The diagnosis of relapse is based on morphological evidence supported by 
cytogenetic and/or molecular testing consistent with disease characteristics noted at 
diagnosis or a relapse prior to transplant. 
11.8 Non-Catheter Associated Bacterial Infection  
All blood or invasive bacterial infections (i.e. excluding surveillance cultures of the nose, 
throat, stool and urine; catheter infections) which are not considered to be a central line-
associated infection (CLABSI) based on published criteria from the U.S. Centers for 
Disease Control, will be considered an event.  A second positive bacterial culture with the 
same organism from the same site will not be considered a new event unless symptoms 
resolved after treatment and negative cultures were documented for at least one week. 
11.9 Event Free Survival (EFS)  
EFS is the patient’s status of being alive with sustained engraftment and in continuous 
complete remission. 
12 Statistical Considerations 
12.1 Study Design, Objectives and Endpoints 
The principal objective of this phase II trial is to determine if transplantation of MGTA-
456 significantly reduces the expected duration of neutropenia relative to that estimated 
in recipients of an unmanipulated single UCB unit transplantation receiving the same 
conditioning and GVHD immunoprophylaxis for hematological malignancy.  The primary 
endpoint of engraftment will be evaluated using a two stage enrollment procedure, while 
TRM, graft failure, and excessive acute GVHD will be monitored using continual 
stopping boundaries. Stage 1 will enroll 18 patients. If 4 or more demonstrate 
engraftment by day 14, an additional 22 patients will be enrolled in stage 2 for a 
maximum total of 40 enrolled patients. If 9 or more demonstrate engraftment in both 
stages combined, the treatment will be considered a success. 
The aim is to evaluate the impact of MGTA-456 containing >10 x 106 CD34 cells/kg. 
Patients may still receive MGTA-456 at lower cell doses (<10 x 106 CD34 cells/kg but >2 
x 106 CD34 cells/kg) but endpoints and stopping rules will be evaluated separately by 
study design.  

MT2018-06                                                          Phase II Trial of MGTA-456 for Hematologic Malignancies 
 
 
 
April 23, 2021 
Page 54 of 68 
CPRC #2018LS051 
12.1.1 Primary Endpoint  
• 
Incidence of neutrophil recovery by day 14 after transplantation 
12.1.2 Secondary and Transplant Related Secondary Endpoints 
• 
Number of days alive without hospitalization between days 0 and 100 after 
transplantation 
• 
Incidence of secondary graft failure 
• 
Incidence of platelet recovery at day 60 
• 
Incidence of TRM at 6 months 
• 
Incidence of grades II-IV and III-IV acute GVHD at day 100 
• 
Incidence of chronic GVHD at 1 year 
• 
Incidence of relapse at 2 years 
• 
Incidence of non-catheter associated bacterial infections by day 100 
• 
Probability of overall survival and event-free survival at 2 years 
12.1.3 Exploratory Endpoints 
• 
Description of immunological recovery 
• 
Incidence of absolute CD4 T cell ≥0.2 x 109/L by day 100 
• 
Incidence of opportunistic infection (viral / fungal) by day 100 
• 
Description of hospital costs by day 100 
• 
Description of number of red cell and platelet transfusions by day 100. 
• 
Assess B and T cell immune reconstitution as well as functional responses 
at day 100 and day 180. 
12.2 Statistical Analysis 
Our primary hypothesis is that subjects transplanted with MGTA-456 will demonstrate 
neutrophil recovery by day 14 at a substantially higher frequency relative to the historical 
estimate for identically treated patients transplanted with unmanipulated UCB.  
Neutrophil engraftment by day 14 will be estimated with simple proportions. Given our 
experience from historical data as well as the pilot data for MGTA-456, it is unlikely that 
there will be any deaths without engraftment prior to day 14. If such a scenario arises, 
however, neutrophil engraftment will be estimated by cumulative incidence, treating non-
event death as a competing risk [41]. Cumulative incidence will also be used to estimate 
platelet recovery, TRM, GVHD, relapse and infection treating non-event deaths or 
relapse in the case of TRM as a competing risk. Simple proportions will be used to 
estimate secondary graft failure among engrafted patients only. Overall survival and 
EFS will be estimated with Kaplan-Meier curves [43]. If assumptions are satisfied, a 
sample mean along with a 95% confidence interval will be used to assess the number of 
surviving discharged days from the hospital prior to day 100 post-transplant. In addition, 
a one-sample t-test will be run to compare the study group average to a null hypothesis 
estimate of 60 days. If assumptions are not satisfied, descriptive statistics such as 
medians, ranges and interquartile ranges will be used. These will similarly be used for 
the endpoints of immune reconstitution and hospital costs. Descriptive endpoints may 
also be summarized with boxplots and dot plots. No specific hypothesis tests will be 

MT2018-06                                                          Phase II Trial of MGTA-456 for Hematologic Malignancies 
 
 
 
April 23, 2021 
Page 55 of 68 
CPRC #2018LS051 
used to investigate B and T cell immune reconstitution or functional response. 
Descriptive statistics such as medians and ranges at days 100 and 180 along with 
descriptive plots will be used to assess these parameters. 
12.3 Rationale for Sample Size 
Although the primary endpoint is the incidence of patients reaching neutrophil recovery 
by day 14, the sample size is based on the more restrictive test for the number of 
surviving hospital-free days prior to day 100. We want to detect a minimum 10 day 
improvement in the average number of days surviving outside of the hospital. Based on 
the historical estimate of 60 days and using a standard deviation of 25.0 from pilot data, 
a sample size of 40 patients will provide 80% power to detect a minimum improvement 
of 10 days over the null hypothesis of 60 days. This power estimate uses a one-sided 
one-sample t-test. In the assessment of our primary endpoint, historical data show that 
the standard control populations have an estimated neutrophil engraftment of 13% by 
day 14 post-HSCT. Pilot data among patients receiving the expanded MGTA-456 unit 
potentially show engraftment of 60% by day 14. We want to detect a minimum 
improvement of 20% (from 13% to 33%). Based on a Simon’s optimal two stage design 
with a type I error of 5%, 40 patients will provide power of 87% [48]. 
12.4 Monitoring Guidelines 
Early stopping rules for excess graft failure, TRM and grade III-IV acute GVHD will be in 
place to monitor safety. In the event that a monitoring boundary is triggered, study 
enrollment will be suspended and the PI, IRB and the Cancer Center’s DSMC will be 
notified.  
The stopping rules were developed using an adaptation of Pocock stopping boundaries 
[44].  
• 
Graft Failure by day 42: We will construct a boundary such that the probability of 
early stopping is at most 5% if the graft failure rate is equal to 5%. The monitoring 
boundary for the MGTA-456 patients will be 2/4, 3/12, 4/21, 5/31 or 6 graft failures 
out of 40 patients. The probability of stopping early if the actual probability of graft 
failure is 20% is 88%. 
• 
TRM by 6 months: We will construct a boundary such that the probability of early 
stopping is at most 5% if the TRM rate is equal to 20%. The monitoring boundary for 
the MGTA-456 patients will be 3/3, 4/5, 5/8, 6/11, 7/14, 8/17, 9/21, 10/24, 11/28, 
12/31, 13/35, 14/38 or 15 deaths out of 40 patients. The probability of stopping early 
if the actual probability of TRM is 40% is 80%.  
• 
Grade III-IV Acute GVHD day 100: We will construct a boundary such that the 
probability of early stopping is at most 5% if the GVHD rate is equal to 15%. The 
monitoring boundary for the MGTA-456 patients will be 3/4, 4/7, 5/10, 6/14, 7/18, 
8/22, 9/27, 10/32, 11/36 or 12 events out 40 patients. The probability of stopping 
early if the actual probability of TRM is 30% is 66%. Operating characteristics are 
calculated using software available at www.bios.unc.edu/∼qaqish/software. 

MT2018-06                                                          Phase II Trial of MGTA-456 for Hematologic Malignancies 
 
 
 
April 23, 2021 
Page 56 of 68 
CPRC #2018LS051 
• 
We understand that inclusion of the stopping rules may slightly reduce the overall 
power of our study. 
12.5 Gender and Ethnicities Statement 
This study is open to both males and females and to all racial/ethnic groups. The patient 
enrollment pattern is expected to be similar to that of other hematological malignancy 
studies. It is not anticipated that the outcome will be affected by either race or gender.  
The study will not have separate accrual targets for different subgroups.  
13 Conduct of the Study 
13.1 Good Clinical Practice 
The study will be conducted in accordance with the appropriate regulatory 
requirement(s).  Essential clinical documents will be maintained to demonstrate the 
validity of the study and the integrity of the data collected.  Master files will be 
established at the beginning of the study, maintained for the duration of the study and 
retained in a centralized file within the Clinical Trials Office of the Masonic Cancer 
Center according to the appropriate regulations.   
13.2 Ethical Considerations 
The study will be conducted in accordance with ethical principles founded in the 
Declaration of Helsinki.  The IRB will review all appropriate study documentation in order 
to safeguard the rights, safety and well-being of the patients.  The study will only be 
conducted at sites where IRB approval has been obtained.  The protocol, consent, 
written information given to the patients, safety updates, annual progress reports, and 
any revisions to these documents will be provided to the IRB by the investigator.   
13.3 Informed Consent 
All potential study participants will be given a copy of the IRB-approved consent to 
review. The investigator or designee will explain all aspects of the study in lay language 
and answer all questions regarding the study. If the participant decides to participate in 
the study, he/she will be asked to sign and date the consent document. Patients who 
refuse to participate or who withdraw from the study will be treated without prejudice. 
 
 

MT2018-06                                                          Phase II Trial of MGTA-456 for Hematologic Malignancies 
 
 
 
April 23, 2021 
Page 57 of 68 
CPRC #2018LS051 
14 References 
 
1) Cheuk DKL. Optimal stem cell source for allogeneic stem cell transplantation for 
hematological malignancies. World. J. Transplant. 2013; 3 (4): 99-112. 
2) Eapen M, Rocha V.  Principles and analysis of hematopoietic stem cell transplantation 
outcomes: the physician’s perspective.  Lifetime Data Anal 2008; 14: 379-88. 
3) Gragert L, Eapen M, Williams E, Freeman J, Spellman S, Baitty R, Hartzman R, Rizzo JD, 
Horowitz M, Confer D, Maiers M. HLA match likelihoods for hematopoietic stem-cell grafts 
in the U.S. Registry.  New Engl J Med 2014;371: 339-348. 
4) Ballen KK, Gluckman E, Broxmeyer HE. Umbilical cord blood transplantation: the first 25 
years and beyond. Blood. 2013; 122 (4): 491-498. 
5) Smith AR, Wagner JE. Alternative hematopoietic stem cell sources for transplantation: 
place of umbilical cord blood. Br. J. Haematol. 2009; 147 (2): 246-61. 
6) Wagner JE, Kernan NA, Steinbuch M, Broxmeyer HE, Gluckman E. Allogeneic sibling 
umbilical-cord-blood transplantation in children with malignant and non-malignant disease. 
Lancet. 1995;346:214-219. 
7) Gluckman E, Rocha V, Boyer-Chammard A, et al. Outcome of cord-blood transplantation 
from related and unrelated donors. Eurocord Transplant Group and the European Blood 
and Marrow Transplantation Group. N Engl J Med. 1997;337:373-381. 
8) Rubinstein P, Adamson JW, Stevens C. The placental/umbilcal cord blood program of the 
New York BloodCenter: a progress report. Ann NY Acad Sci. 2006;872:328–35. 
9) Hackenberg P, Kögler G, Wernet P. NETCORD: a cord blood allocation network. Bone 
Marrow Transplant. 1998;22:S17– 8. 
10) Lazzari L, Corsini C, Curioni C, Lecchi L, Scalamogna M, Rebulla P, et al. The Milan Cord 
Blood Bank the Italian Cord Blood Network. J Hematother. 1996;5:117–22. 
11) Barker JN. Umbilical cord blood (UCB) transplantation: an alternative to the use of 
unrelated volunteer donors? Hematology (Am Soc Hematol Educ Program) 2007; 
2007:55-61 
12) Brunstein CG, Gutman JA, Weisdorf DJ, Woolfrey AE, Defor TE, Gooley TA, et al. 
Allogeneic hematopoietic cell transplantation for hematological malignancy:  Relative risks 
and benefits of double umbilical cord blood. Blood. 2010;116:4693-9 
13) Verneris MR, Brunstein CG, Barker J, et al. Relapse risk after umbilical cord blood 
transplantation: enhanced graft-versus-leukemia effect in recipients of 2 units. Blood. 
2009;114:4293-4299. 
14) Rocha V, Labopin M, Mohty M, et al. Outcomes after double unit unrelated cord blood 
transplantation compared to single UCBT in adults with acute leukemia in remission: An 
Eurocord ELWP Collaboration Study. Blood. 2010;116:401 
15) Showel M, Fuchs EJ.  Recent developments in HLA-haploidentical transplantations.  Best 
Pract Res Clin Haematol 2015; 28: 141-6. 
16) Kasamon YL, Bolaños-Meade J, Prince GT, et al.  Outcomes of nonmyeloablative HLA-
haploidentical blood or marrow transplantation with high-dose post-transplantation 
cyclophosphamide in older adults.  J Clin Oncol 2015; 33: 3152-61. 
17) Shaw BE.  Related haploidentical donors are a better choice than matched unrelated 
donors: Counterpoint.  Blood Advances 2017; 1: 401-406.  

MT2018-06                                                          Phase II Trial of MGTA-456 for Hematologic Malignancies 
 
 
 
April 23, 2021 
Page 58 of 68 
CPRC #2018LS051 
18) Wagner JE, Barker JN, DeFor TE, Baker KS, Blazar BR, Eide C, Goldman A, Kersey J, 
Krivit W, MacMillan ML, Orchard PJ, Peters C, Weisdorf DJ, Ramsay NK, Davies SM. 
Transplantation of unrelated donor umbilical cord blood in 102 patients with malignant and 
nonmalignant diseases: influence of CD34 cell dose and HLA disparity on treatment-
related mortality and survival. Blood 2002;100: 1611-8. 
19) Kurtzberg J, Prasad VK, Carter SL, Wagner JE, Baxter-Lowe LA, Wall D, et al. Results of 
the Cord Blood Transplantation Study (COBLT): clinical outcomes of unrelated donor 
umbilical cord blood transplantation in pediatric patients with hematologic malignancies. 
Blood. 2008;112:4318-27. 
20) Barker JN, Weisdorf DJ, DeFor TE, Blazar BR, Miller JS, Wagner JE. Transplantation of 
two partially HLA matched umbilical cord blood units to enhance engraftment in adults with 
hematological malignancy. Blood. 2005; 105 (3): 1343-7. 
21) Brunstein CG, Barker JN, Weisdorf DJ, DeFor TE, Miller JS, Blazar BR, McGlave PB, 
Wagner JE. Umbilical cord blood transplantation after nonmyeloablative conditioning: 
impact on transplantation outcomes in 110 adults with hematological disease. Blood. 
2007; 110 (8): 3064-70. 
22) Wagner JE, Jr., Eapen M, Carter S, Wang Y, Schultz KR, Wall DA, et al. One-unit versus 
two-unit cord-blood transplantation for hematologic cancers. N Engl J Med. 2014; 371: 
1685-94. 
23) Eapen M, Kurtzberg J, Zhang M-J, Hattersely G, Fei M, Mendizabal A, Chan KW, De 
Oliveira S, Schultz KR, Wall D, Horowitz MM, Wagner JE.  Umbilical Cord Blood 
Transplantation in Children with Acute Leukemia: Impact of Conditioning on 
Transplantation Outcomes.  Biol Blood Marrow Transplant 2017; 23: 1714–1721. 
24) Wagner JE, Brunstein CG, Boitano AE, DeFor TE, McKenna D, Sumstad D, Blazar BR, 
Tolar J, Le C, Jones J, Cooke CP, Bleul CC. Safety and efficacy of StemRegenin-1 
expanded umbilical cord blood hematopoietic cells after myeloablative conditioning.  Cell 
Stem Cell 2016;18:144-55. 
25) Boitano, A. E.,Wang, J.,Romeo, R.,Bouchez, L. C.,Parker, A. E.,Sutton, S. E.,Walker, J. 
R.,Flaveny, C. A.,Perdew, G. H.,Denison, M. S.,Schultz, P. G.,Cooke, M. P. Aryl 
hydrocarbon receptor antagonists promote the expansion of human hematopoietic stem 
cells. Science 2010, 329 (5997), 1345-8. 
26) de Lima M, McMannis J, Gee A, Komanduri K, Couriel D, Andersson BS, Hosing C, 
Khouri I, Jones R, Champlin R, et. al. Transplantation of ex vivo expanded cord blood cells 
using the copper chelator tetraethylenepentamine: a phase I/II clinical trial.  Bone Marrow 
Transplant. 2008; 41 (9): 771-8. 
27) Delaney C, Heimfeld S, Brashem-Stein C, Voorhies H, Manger RI, Bernstein ID.  Notch-
mediated expansion of human cord blood progenitor cells capable of rapid myeloid 
reconstitution.  Nat. Med. 2010; 16 (2): 232-6. 
28) de Lima M, McNiece I, Robinson SN, Munsell M, Eapen M, Horowitz M, Alousi A, Saliba 
R, McMannis JD, Kaur I, et.al. Cord-blood engraftment with ex vivo mesenchymal-cell 
culture.  New Engl. J. Med. 2012; 367 (24): 2305-15. 
29) Horwitz ME, Chao NJ, Rizzieri DA, Long GD, Sullivan KM, Gasparetto C, Chute JP, Morris 
A, McDonald C, Waters-Pick B, et. al. Umbilical cord blood expansion with nicotinamide 
provides long-term multi-lineage engraftment. J. Clin. Invest. 2014; 124 (4): 3121-8. 

MT2018-06                                                          Phase II Trial of MGTA-456 for Hematologic Malignancies 
 
 
 
April 23, 2021 
Page 59 of 68 
CPRC #2018LS051 
30) Radtke S, Gorgens A, Kordelas L, Schmidt M, Kimmig KR, Koninger A, Horn PA, Giebel 
B.  CD133 allows elaborated discrimination and quantification of haematopoietic 
progenitor subsets in human haematopoietic stem cell transplants.  Brit J Haematol 2015; 
169: 868-878. 
31) Wong WM, Sigvardsson M, Astrand-Grundstom I, Hogge D, Larsson J, Qian H, Ekblom M.  
Expression of integrin α2 receptor in human cord blood CD34+CD38-CD90+ stem cells 
engrafting long-term in NOD/SCID-IL2Rc null mice.  Stem Cells 2013; 31:360-371. 
32) Gutman JA, Turtle CJ, Manley TJ, Heimfeld S, Riddell SR, Delaney C.  Single-unit 
dominance after double-unit umbilical cord blood transplantation coincides with a specific 
CD8+ T-cell response against the nonengrafted unit.  Blood. 2010; 115 (4): 757-785. 
33) Ramirez P, Wagner JE, DeFor TE, Blazar BR, Verneris MR, Miller JS, McKenna DH, 
Weisdorf DJ, McGlave PB, Brunstein CG.  Factors predicting single-unit predominance 
after double umbilical cord blood transplantation.  Bone Marrow Transplant. 2012; 47 (6): 
799-803. 
34) Lund TC, Boitano AE, Delaney CS, Shpall EJ, Wagner JE.  Advances in umbilical cord 
blood manipulation-from niche to bedside. Nat Rev Clin Oncol. 2015;12:163-74. 
35) Yahata T, Ando K, Miyatake H, Uno T, Sato T, Ito M, Kato S, Hotta T.  Competitive 
repopulation assay of two gene-marked cord blood units in NOD/SCID/gammac(null) 
mice.  Mol Ther 2004; 10: 882-91. 
36) Shu Z, Heimfeld S, Gao D. Hematopoietic SCT with cryopreserved grafts:  adverse 
reactions after transplantion and cryoprotectant removal before infusion, Bone Marrow 
Transplant 2014; 49: 469-476. 
37) Konuma T,  Ooi J, Takahashi S, Tomonari A, Tsukada N, Kobayashi T, Sata A, Kato S, 
Kasahara S, Ebihara Y, Nagamura-Inoue T, Tsuji K, Tojo A, Asano S. Cardiovascular 
toxicity of cryopreserved cord blood cell infusion, Bone Marrow Transplant 2008; 41: 861-
865. 
38) Regan DM, Wofford JD, Wall DA. Comparison of cord blood thawing methods on cell 
recovery, potency, and infusion. Transfusion. 2010; 50:2670-75. 
39) Kharbanda S, Smith AR, Hutchinson SK, McKenna DH, Ball JB, Lamb LS, Agarwal R, 
Weinberg KI, Wagner JE. Unrelated donor allogeneic hematopoietic stem cell 
transplantation for patients with hemoglobinopathies using a reduced- intensity 
conditioning regimen and third-party mesenchymal stromal cells. Biol Blood Marrow 
Transplant.2014; 20:581-586. 
40) Martín-Henao GA, Resano PM, Villegas JM, Manero PP, Sánchez JM, Bosch MP, Codins 
AE, Bruguera MS, Infante LR, Oyarzabal AP, Soldevila RN, Caiz DC, Bosch LM, Barbeta 
EC, Ronda JR. Adverse reactions during transfusion of thawed haematopoietic progenitor 
cells from apheresis are closely related to the number of granulocyte cells in the 
leukapheresis product. Vox Sang. 2010; 99:267-73. 
41) Lin, DY. Non-parametric inference for cumulative incidence functions in competing risks 
studies. Statistics in Medicine 1997, 16 (8), 901-10. 
42) Gray RJ. A class of K-sample tests for comparing the cumulative incidence of a competing 
risk. Ann Stat. 1988;16:1141-54. 
43) Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J  Am Stat 
Assoc. 1958;53:457-81. 

MT2018-06                                                          Phase II Trial of MGTA-456 for Hematologic Malignancies 
 
 
 
April 23, 2021 
Page 60 of 68 
CPRC #2018LS051 
44) Ivanova A, Qaqish B, Schell M. Continuous toxicity monitoring in phase II trials in 
oncology. Biometrics. 2005 61:540-, 2005. 
45) Park BG, Park CJ, Jang S, et al. Reconstitution of lymphocyte subpopulations after 
hematopoietic stem cell transplantation: comparison of hematologic malignancies and 
donor types in event-free patients. Leuk Res. 2015;39(12):1334-1341. 
46) Abdel-Azim H, Elshoury A, Mahadeo KM, Parkman R, Kapoor N. Humoral Immune 
Reconstitution Kinetics after Allogeneic Hematopoietic Stem Cell Transplantation in 
Children: A Maturation Block of IgM Memory B Cells May Lead to Impaired Antibody 
Immune Reconstitution. Biol Blood Marrow Transplant. 2017;23(9):1437-1446. 
47) Wagner JE, Brunstein C, McKenna D, et al. StemRegenin-1 (SR1) Expansion Culture 
Abrogates the Engraftment Barrier Associated with Umbilical Cord Blood Transplantation 
(UCBT). Vol. 124; 2014. 
48) Simon R. Optimal two-stage designs for Phase II Clinical Trials. Controlled Clinical Trials 
1989;10:1-10. 
 

MT2018-06                                                          Phase II Trial of MGTA-456 for Hematologic Malignancies 
 
 
 
April 23, 2021 
Page 61 of 68 
CPRC #2018LS051 
Appendix I – Karnofsky and Lansky Scales 
 
Karnofsky Scale (recipient age ≥ 16 years)  
Lansky Scale (recipient age <16 years)  
Able to carry on normal activity; no special care is needed  Able to carry on normal activity; no special care 
is needed  
100 Normal, no complaints, no evidence of disease  
100 Fully active  
90 Able to carry on normal activity 
90 Minor restriction in physically strenuous play 
80 Normal activity with effort  
80 Restricted in strenuous play, tires more easily, 
otherwise active 
Unable to work, able to live at home cares for most 
personal needs, a varying amount of assistance is needed  Mild to moderate restriction 
70 Cares for self, unable to carry on normal activity or to do 
active work 
70 Both greater restrictions of, and less time spent in 
active play 
60 Requires occasional assistance but is able to care for most 
needs  
60 Ambulatory up to 50% of time, limited active play 
with assistance/supervision 
50 Requires considerable assistance and frequent medical 
care  
50 Considerable assistance required for any active 
play, fully able to engage in quiet play 
Unable to care for self, requires equivalent of institutional 
or hospital care, disease may be progressing rapidly  
Moderate to severe restriction 
40 Disabled, requires special care and assistance  
40 Able to initiate quite activities  
30 Severely disabled, hospitalization indicated, although death 
not imminent  
30 Needs considerable assistance for quiet activity 
20 Very sick, hospitalization necessary  
20 Limited to very passive activity initiated by others 
(e.g., TV) 
10 Moribund, fatal process progressing rapidly  
10 Completely disabled, not even passive play 
 
https://www.cibmtr.org/manuals/fim/1/en/topic/appendix-l-karnofsky-lansky-performance-status 
 
Lansky scale above will only be applied to children aged 2-15 years, inclusive.  For children <2 
years, scores will be severe, mild to moderate or no restrictions: 
Levels of Restriction: 
Severe  
 
All activities require more than any age appropriate assistance  
Mild to moderate 
Some activities require more than age appropriate assistance 
None  
 
All activities require assistance that is age appropriate 
 

MT2018-06                                                          Phase II Trial of MGTA-456 for Hematologic Malignancies 
 
 
 
April 23, 2021 
Page 62 of 68 
CPRC #2018LS051 
Appendix II - Recommended TBI Guidelines 
 
Fractionated Total Body Irradiation (In Lateral Position): 
 
1320 cGy administered in an 8 fractions of 165 cGy each with 2 fractions being given each day. 
 
Total body irradiation is given at a dose rate of 10-19 cGy/minute prescribed to the midplane of 
the patient at the level of the umbilicus. 
 
The total body irradiation will be delivered with right and left lateral fields, with the patient supine 
on a specially designed couch. 
 
Based on measurements of transverse thicknesses, aluminum compensators will be used to 
ensure that the dose homogeneity across the field is within 10 % of the prescribed dose.  Usually 
head/neck, leg and lung compensators are used (although based on calculated mid-mediastinal 
doses, lung compensators are often not needed). 
 
Total body irradiation will be delivered with a linear accelerator using 6, 10, and 18 MeV X-rays.  
The energy used will be based on the calculated dose to the midline at points up and down the 
patient's torso.  The lowest energy that gives 90-100% of the prescription point dose will be used. 
 
A beam "spoiler" will be used to ensure a full skin dose. 
 
Half value layer lung and kidney blocks will not be utilized. 
 
Testicular boosts should be used for all males with ALL (and according to institutional practice for 
other diseases).  The testicular boost is given in a single 400 cGy fraction with either electrons 
prescribed to Dmax or photons prescribed to the midplane of the scrotum.  If electrons are used, 
the energy for the testicular boost depends on the thickness of the testicles and is chosen so that 
the D90 corresponds > to the posterior surface of the scrotum.  
 
 

MT2018-06                                                          Phase II Trial of MGTA-456 for Hematologic Malignancies 
 
 
 
April 23, 2021 
Page 63 of 68 
CPRC #2018LS051 
Appendix III – Busulfan Dose Selection, AUC Monitoring and Algorithm 
for Dose Modification Using Once Daily IV Dosing 
This protocol will use once daily (every 24 hour) intravenous BU dosing. Four (4) total doses of 
BU will be given over 4 days in the preparative regimen.  AUC determination after each of the first 
3 doses will be performed (AUC1, AUC2, and AUC3 following Doses #1, #2 and #3, respectively). 
For all patients, each busulfan dose will be administered over 3 hours by central venous line per 
University of Minnesota BMT Program standard guidelines..  
 
THE TOTAL regimen busulfan AUC (AUCcum) targeted will be = 14,080-16,400 (µM·Min)/L [57.7-
67.2 (mg · h)/L] with ideal target AUCcum of 15,200 (µM·Min)/L [62 (mg · h)/L] in order to best 
optimize engraftment while minimizing toxicity. If at any time upon interim analysis and review of 
patients transplanted on this protocol with the principal investigators and pharmacy team, the 
subsequent busulfan levels (following doses #2 and #3) are deemed reasonable and consistent, 
the decision may be made to only do kinetics with the first dose for all remaining patients treated 
on this protocol. In that event, kinetics for a subsequent dose (i.e. AUC monitoring) may be 
performed whenever a dose change is required but will not be mandatory. These protocol 
changes (if enacted) will not require a treatment deviation or protocol amendment. 
 
Steady State Concentration (Css) equivalent to 14,080-16,400 (µM·Min)/L = 600-700 
ng/ml 
 
DETERMINATION OF FIRST BUSULFAN DOSE (DOSE #1)  
The initial empiric busulfan dosing (Dose #1) for ALL patients will be determined as follows:  
a. For patients weighing <12 kg: initial dose will be based on the formula according to the 
population PK model developed by Long-Boyle.  
b. For patients weighing ≥12kg and <66 kg: initial dose will be determined by the nomogram 
adapted from Bartelink.  
c. For patients weighing ≥66kg: initial busulfan dose = 3 mg/kg IV Once Daily 
 
1. For patients <12 kg: the first busulfan dose will be based on the population PK 
formula developed by Long-Boyle which calculates the first dose as a function of 
weight and age:  
• 
Use the Dosing Calculator (Long-Boyle Busulfan 1st Dose) on the BMT website 
to determine the precise dose for the patient;  
• 
Age: enter the age in years (to the hundredths place) by dividing the patient’s age in 
days by 365 
• 
Weight: enter the weight in kg (to the tenths place)  
• 
The Calculator is constructed using the following function:  
o Dose (mg) = AUC(target) x CLi  
o AUC(target) = 15.6 mg·hr·L-1 (equivalent to 3800 μM·min∙L-1)  
o CLi is a function of weight and age  
 
CLi = 2.3 L/h x (Matmag + (1- Matmag) x [1-e(-age x Kmat)]) x (weight/8 
kg)0.75 
 
Maturation magnitude (Matmag) = 0.46; Maturation rate constant 
(kmat) = 1.4 

MT2018-06                                                          Phase II Trial of MGTA-456 for Hematologic Malignancies 
 
 
 
April 23, 2021 
Page 64 of 68 
CPRC #2018LS051 
• 
See Table A-1 below for EXAMPLE first Busulfan doses for hypothetical children 
under 12 kg; this table can be used to ensure your patient's calculator output does not 
carry significant error. However, the patient's first dose should be determined directly 
from the calculator.  
 
 
Table A-1: Sample First Busulfan Doses for Various Ages and Weights Using the 
Long-Boyle Method for Determination of First Busulfan Dose for patients < 12 kg & 
for ideal target AUCcum of 15,200 (µM·Min)/L [62 (mg · h)/L. Use this table to check 
against error from the calculator. 
 
 
Sample Age 
 
Sample Weight (kg) 
 
1st Busulfan Dose Per  
Long-Boyle Method (mg) 
1 month 
(0.08 years) 
 
4 
11 
4.4 
11.9 
5 
13 
3 months 
(0.25 years) 
 
5.8 
17.4 
6.4 
18.7 
6.8 
19.6 
6 months 
(0.50 years) 
 
7.2 
24.1 
7.8 
25.5 
8.4 
27 
9 months 
(0.75 years) 
 
8.2 
29.4 
9 
31.6 
9.6 
33.1 
12 months 
(1 years) 
 
9.6 
35.4 
10.2 
37.1 
11 
39.2 
15 months 
(1.25 years) 
 
10.2 
38.8 
11 
41 
11.8 
43.3 
 
2. For patients >/= 12 kg to <66 kg: the first busulfan dose will be according to weight-
based dosing nomogram developed by Bartelink, which determines the first dose as a 
function of weight only.  
• 
Determine the first dose directly from the nomogram chart (no calculator is 
used)  
• 
Round the patient's weight to the nearest kg. For weights in kg ending in "x.5", 
round UP to the nearest kg. For instance, for a weight of 43.5 kg, use 44 kg to 
determine the first busulfan dose from the nomogram.  
• 
See Table A-2 for nomogram 
 
 
 
 
 
 
 
 
 
 

MT2018-06                                                          Phase II Trial of MGTA-456 for Hematologic Malignancies 
 
 
 
April 23, 2021 
Page 65 of 68 
CPRC #2018LS051 
Table A-2: Nomogram for the Determination of First Busulfan Dose for Patients ≥ 12 kg 
and < 66kg for ideal target AUCcum of 15,200 (µM·Min)/L [62 (mg · h)/L.  (Adapted from 
Bartelink).  
Round the patient's weight to the nearest kg in order to determine the first busulfan dose 
from this nomogram 
 
 
Weight 
(kg) 
Dose 
(mg) 
Weight 
(kg) 
Dose 
(mg) 
Weight 
(kg) 
Dose 
(mg) 
Weight 
(kg) 
Dose 
(mg) 
Weight 
(kg) 
Dose 
(mg) 
Weight 
(kg) 
Dose 
(mg) 
 
 
20 
64.7 
30 
86.3 
40 
 103.5 
50 
 117.8 
60 
130.5 
 
 
21 
67.1 
31 
88.2 
41 
105 
51 
119.1 
61 
131.6 
12 
41.8 
22 
69.5 
32 
90.2 
42 
106.5 
52 
120.5 
62 
132.6 
13 
45 
23 
71.9 
33 
92.1 
43 
108 
53 
 121.8 
63 
133.7 
14 
48.2 
24 
74.3 
34 
94.1 
44 
109.5 
54 
123.2 
64 
134.7 
15 
51.2 
25 
76.5 
35 
96 
45 
111 
55 
 124.5 
65 
135.8 
16 
54 
26 
78.5 
36 
97.5 
46 
112.4 
56 
125.7 
 
 
17 
56.8 
27 
80.4 
37 
99 
47 
113.7 
57 
126.9 
 
 
18 
59.5 
28 
82.4 
38 
100.5 
48 
115.1 
58 
128.1 
 
 
19 
62.2 
29 
84.3 
39 
102 
49 
116.4 
59 
129.3 
 
 
 
3.  For patients weighing ≥ 66kg: first busulfan dose = 3 mg/kg IV. 
 
 
BUSULFAN THERAPEUTIC DRUG MONITORING (TDM)  
 
Area under the curve (AUC) analyses will be calculated in-house per University of 
Minnesota BMT standard guidelines for all patients. The AUC will be calculated for each 
dose using serum busulfan concentrations (in ng/ml) performed by the University of 
Minnesota Medical Center Drug Analysis Lab and obtained at the following time-points:  
• Immediately prior to busulfan infusion (*ONLY to be drawn if obtaining 
levels with doses 2, 3 or 4)  
• Immediately after the end of the busulfan infusion  
• 15 minutes after the end of the busulfan infusion  
• 1 hour after the end of the busulfan infusion  
• 3 hours after the end of the busulfan infusion  
• 5 hours after the end of the busulfan infusion  
• 7 hours after the end of the busulfan infusion  
 
* “trough” or pre-dose serum busulfan level will only be obtained when performing 
AUC on 2nd or higher doses, as serum busulfan level prior to dose #1 is assumed 
to be zero.  
 
After determination of the patient's clearance and AUC, subsequent doses will be 
calculated linearly to achieve a goal cumulative AUC exposure.  
 
For patients receiving 4 total busulfan doses the goal AUCcum = 14,080-16,400 
(µM·Min)/L [57.7-67.7 (mg · h)/L] with ideal target AUCcum of 15,200 (µM·Min)/L [62 (mg 
· h)/L] 
 

MT2018-06                                                          Phase II Trial of MGTA-456 for Hematologic Malignancies 
 
 
 
April 23, 2021 
Page 66 of 68 
CPRC #2018LS051 
 
GUIDELINES FOR CHANGING SUBSEQUENT BUSULFAN DOSES BASED ON A 
PATIENT'S TDM RESULTS  
 
Subsequent busulfan dose changes will be made according to the following guidelines:  
 
1. The goal cumulative AUC range (AUCcum for the entire 4-dose course) will be 
14,080-16,400 (µM·Min)/L [57.7-67.7 (mg · h)/L] with ideal target AUCcum of 
15,200 (µM·Min)/L [62 (mg · h)/L] 
2. Cumulative AUC is defined as the sum of each individual dose AUC:  
AUCcum = AUC1 + AUC2 + AUC3 + AUC4  
3. Patients will undergo Dose #1 AUC analysis (AUC1), Dose #2 AUC analysis 
(AUC2) and Dose #3 AUC analysis (AUC3).  
4. Changes will be made to subsequent doses only if the projected AUCcum falls 
outside of the goal range  
a. After the first busulfan dose, projected AUCcum = AUC1 x 4  
b. After the second busulfan dose, projected AUCcum = AUC1 + [AUC2 x 
3]  
c. After the third busulfan dose, projected AUCcum = AUC1 + AUC2 + 
[AUC3 x 2]  
 
5. If dose adjustment is necessary, new doses will be calculated based on an 
ideal target AUCcum of exactly 15,200 μM·min∙L-1 [62 (mg · h)/L].  
 
REFERENCES 
1) Bartelink IH. Body weight-dependent pharmacokinetics of busulfan in paediatric 
haematopoietic stem cell transplantation patients: towards individualized dosing. Clin 
Pharmacokinet. 2012;51:331-45. 
2) Bartelink IH, van Kesteren C, Boelens JJ, Egberts TC, Bierings MB, Cuvelier GD, Wynn RF, 
Slatter MA, Chiesa R, Danhof M, Knibbe CA. Predictive performance of a busulfan 
pharmacokinetic model in children and young adults. Ther Drug Monit. 2012;34:574-83. 
3) Savic RM, Cowan MJ, Dvorak CC, Pai SY, Pereira L, Bartelink IH, Boelens JJ, Bredius RGM, 
Wynn RF, Cuvelier GDE, Shaw PJ, Slatter MA, Long-Boyle J.  Effect of weight and maturation 
on busulfan clearance in infants and small children undergoing hematopoietic cell 
transplantation.  Biol Blood Marrow Transplant. 2013;19:1608-1614. 
 
 

MT2018-06                                                          Phase II Trial of MGTA-456 for Hematologic Malignancies 
 
 
 
April 23, 2021 
Page 67 of 68 
CPRC #2018LS051 
Appendix IV - GVHD Scoring 
 
Organ involvement will be staged using the criteria outlined in the table below.  Biopsy of each 
organ site at diagnosis or major change in disease activity will be performed unless clinical 
circumstances make it impossible. 
Consensus Clinical Stage and Grade of Acute GVHD (Przepiorka et al, 1995) 
Stage 
Skin 
Liver 
Lower 
Gastrointestinal 
Tract 
Upper 
Gastrointestinal 
Tract 
1 
Maculopapular rash 
<25% of body 
surface 
Bilirubin 2.0 – 3.0 
mg/dl 
Diarrhea 500 – 1000 
mL/day or 280 – 555 
mL/m2 
No protracted 
nausea and 
vomiting 
2 
Maculopapular rash 
25-50% body 
surface 
Bilirubin 3.1 – 6.0 
mg/dl 
Diarrhea 1001 – 1500 
mL/day or 556 – 833 
mL/m2 
Persistent nausea, 
vomiting or anorexia 
3 
Generalized 
erythroderma 
Bilirubin 6.1 – 15.0 
mg/dl 
Diarrhea >1500 
mL/day or >833 mL/m2 
 
4 
Generalized 
erythroderma with 
bullous formation 
and desquamation 
Bilirubin > 15 mg/dl 
Severe abdominal 
pain, with or without 
ileus, or stool with 
frank blood or melena 
 
 
Grading for Treatment Criteria: 
Mild GVHD  
 
Skin stage I-II only (Equivalent to Seattle Grade I). 
Moderate GVHD 
Skin stage I-III and/or liver I-IV and/or Gastrointestinal tract (GI) I-III and/or
 
Upper GI (UGI).  (Equivalent to Seattle Grade II, III). 
Severe GVHD Any stage IV along with severe clinical illness. 
Late Acute and Chronic GVHD 
Late acute and chronic GVHD will be assessed using the National Institutes of Health (NIH) 
Consensus Criteria. 
 
 

MT2018-06                                                          Phase II Trial of MGTA-456 for Hematologic Malignancies 
 
 
 
April 23, 2021 
Page 68 of 68 
CPRC #2018LS051 
Appendix V – Targeted Toxicities 
MT2018-06  
 
  
 
 
 
 
Refer to section 9.2.2 for time points  
Patient Initials:  _______ 
Date of Assessment:  _________     Assessment Time Point:  _________  
Toxicity 
Grade 0 Grade 1 
Grade 2 
Grade 3 
Grade 4 
Infusion Related 
Reaction 
None 
Mild transient reaction; 
infusion interruption not 
indicated; intervention not 
indicated 
Therapy or infusion interruption 
indicated but responds promptly to 
symptomatic treatment (e.g., 
antihistamines, NSAIDS, narcotics, 
IV fluids); prophylactic medications 
indicated for < 24 hrs 
Prolonged (e.g., not rapidly responsive 
to symptomatic medication and/or brief 
interruption of infusion); recurrence of 
symptoms following initial 
improvement; prolongation of 
hospitalization for clinical sequelae 
Life-threatening 
consequences; urgent 
intervention indicated 
Bronchospasm 
None 
Mild symptoms; intervention 
not indicated 
Symptomatic; medical intervention 
indicated; limiting instrumental 
ADL 
Limiting self-care ADL; oxygen 
saturation decreased 
Life-threatening respiratory 
or hemodynamic 
compromise; intubation or 
urgent intervention indicated 
Dyspnea/ 
Wheezing 
None 
Shortness of breath with 
moderate exertion 
Shortness of breath with minimal 
exertion; limiting instrumental ADL 
Shortness of breath at rest; limiting 
self- care ADL 
Life-threatening 
consequences; urgent 
intervention indicated 
Hypoxia 
None 
Decreased oxygen 
saturation with exercise 
(e.g., pulse oximeter < 
88%); intermittent 
supplemental oxygen 
Decreased oxygen saturation at 
rest (e.g., pulse oximeter < 88% or 
PaO2 < =55 mm Hg) 
 
Life-threatening airway compromise; 
urgent intervention indicated (e.g., 
tracheotomy or intubation 
Life-threatening airway 
compromise; urgent 
intervention indicated (e.g., 
tracheotomy or intubation 
Fever 
None 
38.0 - 39.0 degrees C 
(100.4 - 102.2 degrees F) 
>39.0 - 40.0 degrees C (102.3 - 
104.0 degrees F) 
>40.0 degrees C (>104.0 degrees F) 
for < 24 hrs 
>40.0 degrees C (>104.0 
degrees F) for >24 hrs 
Chills 
None 
Mild sensation of cold; 
shivering; chattering of teeth 
Moderate tremor of the entire 
body; narcotics indicated 
Severe or prolonged, not responsive 
to narcotics 
Life Threatening 
Hypertension 
None 
Prehypertension (systolic 
BP 120 - 139 mm Hg or 
diastolic BP 80 - 89 mm Hg) 
Stage 1 hypertension (systolic BP 
140 - 159 mm Hg or diastolic BP 
90 -99 mm Hg); medical 
intervention indicated; recurrent or 
persistent (>24 hrs); symptomatic 
increase by >20 mm Hg (diastolic) 
or to >140/90 mm Hg if previously 
WNL; monotherapy indicated; 
Pediatric: recurrent or persistent 
(>24 hrs) BP >ULN; monotherapy 
indicated 
Stage 2 hypertension (systolic BP >= 
160 mm Hg or diastolic BP >=100 mm 
Hg); medical intervention indicated; 
more than one drug or more intensive 
therapy than previously used 
indicated; Pediatric: Same as adult 
Life-threatening 
consequences (e.g. 
malignant hypertension, 
transient or permanent 
neurologic deficit, 
hypertensive crisis); urgent 
intervention indicated; 
Pediatric: Same as adult 
Hypotension 
None 
Asymptomatic, intervention 
not indicated 
Non-urgent medical intervention 
indicated 
Medical intervention or hospitalization 
indicated 
Life-threatening and urgent 
intervention indicated 
Sinus 
Bradycardia 
None 
Asymptomatic, intervention 
not indicated 
Symptomatic, medical intervention 
indicated 
Severe, medically significant, medical 
intervention indicated 
Life-threatening 
consequences; urgent 
intervention indicated 
Sinus 
Tachycardia 
None 
Asymptomatic, intervention 
not indicated 
Symptomatic; non-urgent medical 
intervention indicated 
Urgent medical intervention indicated 
Life Threatening 
Vomiting 
None 
1 - 2 episodes (separated by 
5 minutes) in 24 hrs 
3 - 5 episodes (separated by 5 
minutes) in 24 hrs 
>6 episodes (separated by 5 minutes) 
in 24 hrs; tube feeding, TPN or 
hospitalization indicated 
Life-threatening 
consequences; urgent 
intervention indicated 
Creatinine 
Normal 
>1-1.5x baseline; >1.5 x LN 
>1.5 - 3.0x baseline; >1.5-3.0x LN 
>3.0 baseline; > 3.0 - 6.0 x ULN 
>6.0 x ULN 
Rash 
None 
Macules/papules covering < 
10% BSA with or without 
symptoms (e.g., pruritus, 
burning, tightness) 
Macules/papules covering 10-30% 
BSA with or without symptoms; 
limiting instrumental ADL 
Macules/papules covering >30% BSA 
with or without associated symptoms; 
limiting self-care ADL 
Life Threatening 
Chest Pain 
None 
Mild pain 
Moderate pain; limiting 
instrumental ADL 
Pain at rest; limiting self-care ADL 
Life Threatening 
Back/Flank Pain 
None 
Mild pain 
Moderate pain; limiting 
instrumental ADL 
Pain at rest; limiting self-care ADL 
Life Threatening 
Flushing 
None 
Asymptomatic; clinical or 
diagnostic observations 
only; intervention not 
indicated 
Moderate symptoms; medical 
intervention indicated; limiting 
instrumental ADL 
Symptomatic, associated with 
hypotension and/or tachycardia; 
limiting self-care ADL 
-------------------- 
Urticaria(Hives) 
None 
Urticarial lesions covering < 
10% BSA; topical 
intervention indicated 
Urticarial lesions covering 10 - 
30% BSA; oral intervention 
indicated 
Urticarial lesions covering >30% BSA; 
IV intervention indicated 
Life Threatening 
Neurologic-  
None 
Mild 
Moderate 
Severe 
Life Threatening  
Other-Specify  
None 
Mild 
Moderate 
Severe 
Life Threatening 
 
Person Completing Form:  
 
 
 
 
 
 
                                      ADL = activities of daily living 
All Events are Expected and Attributable Except: