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

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

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.

Study Overview

• Status: Terminated
• Conditions: Acute Lymphoblastic Leukemia; Myelodysplastic Syndrome; Acute Myelogenous Leukemia; Healthy Donors; Related Donors Donating PBSC to a Family Member
• Intervention / Treatment: Biological: MGTA-145; Biological: 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.

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope National Medical Center
    • Stanford, California, United States, 94305
      • Stanford Health Care
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University Hospital
  • Minnesota
    • Rochester, Minnesota, United States, 55902
      • Mayo Clinic Rochester
  • New York
    • Buffalo, New York, United States, 14203
      • Roswell Park Cancer Institute
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State Medical Center, James Cancer Center
  • Texas
    • Houston, Texas, United States, 77030
      • M.D. Anderson Cancer Center
  • Washington
    • Seattle, Washington, United States, 98101
      • Be The Match Collection Center Seattle

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HSC Yield in Apheresis Product	Number of subjects with adequate number of hematopoietic stem cells (≥ 2.0 x 10^6 CD34+ cells/kg) 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
Graft Durability	The proportion of participants with primary and secondary graft failure after transplantation of hematopoietic cells mobilized with MGTA-145 + plerixafor	Day 28
Graft-versus Host Disease (GVHD)	To determine the incidence of acute and chronic graft versus host disease (GVHD) after transplantation of hematopoietic cells mobilized with MGTA-145 + plerixafor	Day 100
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 100
Overall Survival	To determine the probability of overall survival after transplantation of hematopoietic cells mobilized with MGTA-145 + plerixafor	Day 100

Collaborators and Investigators

• Sponsor: Ensoma
• Collaborators: National Marrow Donor Program
• Investigators: Study Chair: Steven Devine, MD, National Marrow Donor Program

Study record dates

Study Major Dates

• Study Start (Actual): June 16, 2021
• Primary Completion (Actual): September 14, 2021
• Study Completion (Actual): March 14, 2022

Study Registration Dates

• First Submitted: February 12, 2021
• First Submitted That Met QC Criteria: February 16, 2021
• First Posted (Actual): February 21, 2021

Study Record Updates

• Last Update Posted (Actual): November 6, 2024
• Last Update Submitted That Met QC Criteria: October 15, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Bone Marrow Diseases; Leukemia, Lymphoid; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Myelodysplastic Syndromes; Anti-Infective Agents; Antiviral Agents; Anti-HIV Agents; Anti-Retroviral Agents; Plerixafor
• Other Study ID Numbers: 145-ADS-202

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No