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

Phase 2

Terminated

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

Interventions: Biological: MGTA-145
Biological: Plerixafor

Registration Number: NCT04762875

Lead Sponsor: Ensoma

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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 7

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Single dose MGTA-145 plus plerixafor followed by apheresis	MGTA-145	MGTA-145 in combination with plerixafor followed by apheresis on one or two consecutive days
Single dose MGTA-145 plus plerixafor followed by apheresis	Plerixafor	MGTA-145 in combination with plerixafor followed by apheresis on one or two consecutive days

Primary Outcome Measures

Name	Time	Method
HSC Yield in Apheresis Product	Up to 2 days	Number of subjects with adequate number of hematopoietic stem cells (≥ 2.0 x 10\^6 CD34+ cells/kg) in one apheresis setting.

Secondary Outcome Measures

Name	Time	Method
Overall Survival	Day 100	To determine the probability of overall survival after transplantation of hematopoietic cells mobilized with MGTA-145 + plerixafor
HSC Yield in Apheresis Product	Up to 2 days	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
Adverse Events Experienced by Donors	Baseline though day 180	To ascertain the incidence of adverse events (AEs) before and during apheresis experienced by donors receiving MGTA-145 + plerixafor
Graft Durability	Day 28	The proportion of participants with primary and secondary graft failure after transplantation of hematopoietic cells mobilized with MGTA-145 + plerixafor
Graft-versus Host Disease (GVHD)	Day 100	To determine the incidence of acute and chronic graft versus host disease (GVHD) after transplantation of hematopoietic cells mobilized with MGTA-145 + plerixafor
Treatment-related Mortality	Day 100	To determine the proportion of treatment-related mortality and disease relapse/progression after transplantation of hematopoietic cells mobilized with MGTA-145 + plerixafor

Trial Locations

Locations (8): City of Hope National Medical Center
🇺🇸
Duarte, California, United States
Stanford Health Care
🇺🇸
Stanford, California, United States
Mayo Clinic Rochester
🇺🇸
Rochester, Minnesota, United States
Roswell Park Cancer Institute
🇺🇸
Buffalo, New York, United States
Ohio State Medical Center, James Cancer Center
🇺🇸
Columbus, Ohio, United States
M.D. Anderson Cancer Center
🇺🇸
Houston, Texas, United States
Be The Match Collection Center Seattle
🇺🇸
Seattle, Washington, United States
Emory University Hospital
🇺🇸
Atlanta, Georgia, United States