MGTA-145 + Plerixafor in the Mobilization of HSCs for Allogeneic Transplant in Hematologic Malignancies

Study Overview
=================
Brief Summary
-----------------
This research study tests a new medicine for mobilizing stem cells so they can be collected and used for allogeneic stem cell transplant for treatment of hematological malignancies. MGTA-145, the new medicine, will be given with plerixafor.

Detailed Description
-----------------
This is a Phase II, open-label, multicenter, prospective study of MGTA-145 + plerixafor mobilized HLA-matched sibling and matched unrelated donor allografts for myeloablative hematopoietic stem cell transplantation (HSCT) in recipients with hematological malignancies. Donors will undergo 1 or 2 days of mobilization and apheresis.

Official Title
-----------------
A Phase II Study Evaluating the Safety and Efficacy of MGTA-145 in Combination With Plerixafor for the Mobilization and Transplantation of HLA-Matched Donor Hematopoietic Stem Cells in Recipients With Hematological Malignancies

Conditions
-----------------
Related Donors Donating PBSC to a Family Member, Healthy Donors, Acute Myelogenous Leukemia, Acute Lymphoblastic Leukemia, Myelodysplastic Syndrome

Intervention / Treatment
-----------------
* Biological: MGTA-145
* Biological: Plerixafor


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Donor Inclusion Criteria: Donor medical suitability and eligibility will be determined following Institution or NMDP/Be The Match standards Age 18-65 years old at the time of signing informed consent 8/8 (HLA- A, B, C, and DRB1) HLA-matched sibling or volunteer unrelated donor Fulfill Institution or NMDP/Be The Match criteria to serve as a mobilized blood cell donor Serum creatinine < 1.5 x institution upper limit of normal (ULN) or estimated creatinine clearance (CRCL) > 50 mL/min using the Modification of Diet in Renal Disease Study (MDRD) equation or similar method Recipient Inclusion Criteria: At least 18 years old at the time of signing informed consent Has an available 8/8 (HLA- A, B, C, and DRB1) HLA-matched sibling or volunteer unrelated donor willing to donate peripheral blood stem cells (PBSC) for transplant Fulfill additional individual Transplant Center Criteria for transplant beyond NMDP/Be The Match criteria One of the following diagnoses: Acute myelogenous leukemia (AML) in 1st remission or beyond with ≤ 5% marrow blasts and no circulating blasts. Documentation of bone marrow assessment will be accepted within 45 days prior to the date of consent. Acute lymphoblastic leukemia (ALL) in 1st remission or beyond with ≤ 5% marrow blasts and no circulating blasts. Documentation of bone marrow assessment will be accepted within 45 days prior to the date of consent. Patients with myelodysplasia (MDS) with no circulating blasts and with less than 10% blasts in the bone marrow (higher blast percentage allowed in MDS due to lack of differences in outcomes with < 5% or 5-10% blasts in MDS). Documentation of bone marrow assessment will be accepted within 45 days prior to the date of consent. Cardiac function: Left ventricular ejection fraction at least 45% based on most recent echocardiogram or MUGA results obtained via standard of care Estimated creatinine clearance acceptable per local institutional guidelines Pulmonary function: diffusing capacity of the lungs for carbon monoxide (DLCO) corrected for hemoglobin at least 50% and forced expiratory volume in first second (FEV1) predicted at least 50% based on most recent DLCO results obtained via standard of care Liver function acceptable per local institutional guidelines Karnofsky performance status (KPS) of 70% or greater Hematopoietic Cell Transplantation-Comorbidity Index (HCT-CI) score of 4 or less Exclusion Criteria: Donor Exclusion Criteria: Donor unwilling or unable to give informed consent, or unable to comply with the protocol including required follow-up and testing Donor already enrolled on another investigational agent study Pregnant or breastfeeding females, sexually active female and male donors not willing or able to use adequate contraception, or males who do not agree to refrain from donating sperm, from the time of consent through 3 months after treatment with MGTA-145 + plerixafor Recipient Exclusion Criteria: Subject unwilling or unable to give informed consent, or unable to comply with the protocol including required follow-up and testing Subject whose donor does not meet the eligibility criteria and is a screen fail Subjects with a prior allogeneic transplant Subjects with active, uncontrolled infection at the time of the transplant preparative regimen Pregnant or breastfeeding females, sexually active female or male subjects not willing or able to use adequate contraception, or males who do not agree to refrain from donating sperm, from the time of consent through 3 months after PBSC infusion Subjects with clinical evidence of active Central Nervous System (CNS) tumor involvement as evidenced by documented disease on examination of spinal fluid or MRI within 45 days of start of conditioning A condition, which, in the opinion of the clinical investigator, would interfere with the evaluation of primary and secondary endpoints Planned treatment with a new investigational agent from the time of transplant through 30 days post-transplant

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single dose MGTA-145 plus plerixafor followed by apheresis<br>MGTA-145 in combination with plerixafor followed by apheresis on one or two consecutive days | Biological: MGTA-145<br>* MGTA-145 will be be administered as an IV infusion<br>Biological: Plerixafor<br>* 240 µg/kg subcutaneously<br>* Other names: Mozobil;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HSC Yield in apheresis product | To assess the efficacy of MGTA-145 in combination with plerixafor in mobilizing adequate number of hematopoietic stem cells (≥ 2.0 x 10^6 CD34+ cells/kg) in healthy donors in one apheresis setting. | Up to 2 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HSC Yield in apheresis product | To determine the proportion of donors whose cells can be successfully mobilized and collected with a target CD34+ cell dose of at least 4.0 x 10^6 CD34+ cells/kg actual recipient weight in one apheresis collection | Up to 2 days | 
| Adverse events experienced by donors | To ascertain the incidence of adverse events (AEs) before and during apheresis experienced by donors receiving MGTA-145 + plerixafor | Baseline though day 180 | 
| Infusion related toxicities | To ascertain the severity of adverse events (AEs) before and during apheresis experienced by donors receiving MGTA-145 + plerixafor | Baseline though 72 hours post donation | 
| Neutrophil and platelet engraftment | To determine the incidence of and kinetics of neutrophil and platelet recovery after transplantation of hematopoietic cells mobilized with MGTA-145 + plerixafor | Day 28, 56, 100, 180, 365 | 
| Graft Durability | The proportion of participants with primary and secondary graft failure after transplantation of hematopoietic cells mobilized with MGTA-145 + plerixafor | Day 28, 56, 100, 180, 365 | 
| Graft-versus host disease (GVHD) | To determine the incidence and severity of acute and chronic graft versus host disease (GVHD) after transplantation of hematopoietic cells mobilized with MGTA-145 + plerixafor | Day 21, 28, 56, 100, 180, and 365 | 
| Treatment-related mortality | To determine the proportion of treatment-related mortality and disease relapse/progression after transplantation of hematopoietic cells mobilized with MGTA-145 + plerixafor | Day 21, 28, 56, 100, 180, and 365 | 
| Progression-free survival | To determine the probability of progression-free survival after transplantation of hematopoietic cells mobilized with MGTA-145 + plerixafor | Day 21, 28, 56, 100, 180, and 365 | 
| Overall survival | To determine the probability of overall survival after transplantation of hematopoietic cells mobilized with MGTA-145 + plerixafor | Day 21, 28, 56, 100, 180, and 365 | 
| Adverse Events related to Allograft | To characterize the adverse effects experienced by recipients receiving grafts mobilized by MGTA-145 + plerixafor | Day 0 through 365 |