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

• ClinicalTrials.gov Identifier: NCT04762875
• Recruitment Status: Recruiting
• First Posted: February 21, 2021
• Last Update Posted: June 14, 2021
• Sponsor: Magenta Therapeutics, Inc.
• Collaborator: National Marrow Donor Program
• Information provided by (Responsible Party): Magenta Therapeutics, Inc.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Related Donors Donating PBSC to a Family Member; Healthy Donors; Acute Myelogenous Leukemia; Acute Lymphoblastic Leukemia; Myelodysplastic Syndrome	Biological: MGTA-145; Biological: Plerixafor	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 56 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Estimated Study Start Date: June 14, 2021
• Estimated Primary Completion Date: August 1, 2022
• Estimated Study Completion Date: August 1, 2023

Arms and Interventions

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 Name: Mozobil

Outcome Measures

Primary Outcome Measures :

1. HSC Yield in apheresis product [ Time Frame: Up to 2 days ]
   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.

Secondary Outcome Measures :

1. HSC Yield in apheresis product [ Time Frame: 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
2. Adverse events experienced by donors [ Time Frame: Baseline though day 180 ]
   To ascertain the incidence of adverse events (AEs) before and during apheresis experienced by donors receiving MGTA-145 + plerixafor
3. Infusion related toxicities [ Time Frame: Baseline though 72 hours post donation ]
   To ascertain the severity of adverse events (AEs) before and during apheresis experienced by donors receiving MGTA-145 + plerixafor
4. Neutrophil and platelet engraftment [ Time Frame: Day 28, 56, 100, 180, 365 ]
   To determine the incidence of and kinetics of neutrophil and platelet recovery after transplantation of hematopoietic cells mobilized with MGTA-145 + plerixafor
5. Graft Durability [ Time Frame: Day 28, 56, 100, 180, 365 ]
   The proportion of participants with primary and secondary graft failure after transplantation of hematopoietic cells mobilized with MGTA-145 + plerixafor
6. Graft-versus host disease (GVHD) [ Time Frame: Day 21, 28, 56, 100, 180, and 365 ]
   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
7. Treatment-related mortality [ Time Frame: Day 21, 28, 56, 100, 180, and 365 ]
   To determine the proportion of treatment-related mortality and disease relapse/progression after transplantation of hematopoietic cells mobilized with MGTA-145 + plerixafor
8. Progression-free survival [ Time Frame: Day 21, 28, 56, 100, 180, and 365 ]
   To determine the probability of progression-free survival after transplantation of hematopoietic cells mobilized with MGTA-145 + plerixafor
9. Overall survival [ Time Frame: Day 21, 28, 56, 100, 180, and 365 ]
   To determine the probability of overall survival after transplantation of hematopoietic cells mobilized with MGTA-145 + plerixafor
10. Adverse Events related to Allograft [ Time Frame: Day 0 through 365 ]
    To characterize the adverse effects experienced by recipients receiving grafts mobilized by MGTA-145 + plerixafor

Eligibility Criteria

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

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

Contacts and Locations

Contacts

Contact: Alisha Mussetter, BS; 763-406-4863; amussett@nmdp.org

Locations

United States, California

City of Hope National Medical Center; Recruiting

Duarte, California, United States, 91010

Contact: Monzr M. Al Malki, MD

Stanford Health Care; Recruiting

Stanford, California, United States, 94305

Contact: Sally Arai, MD

United States, Massachusetts

Massachusetts General Hospital; Recruiting

Boston, Massachusetts, United States, 02114

Contact: Yi-Bin Chen, MD

United States, Minnesota

Mayo Clinic Rochester; Not yet recruiting

Rochester, Minnesota, United States, 55902

Contact: Mark Litzow, MD

United States, Missouri

Washington University/St. Louis Children's Hospital; Not yet recruiting

Saint Louis, Missouri, United States, 63110

Contact: Peter Westervelt, MD, PhD

United States, New York

Roswell Park Cancer Institute; Recruiting

Buffalo, New York, United States, 14203

Contact: Philip McCarthy, MD

United States, Ohio

Ohio State Medical Center, James Cancer Center; Not yet recruiting

Columbus, Ohio, United States, 43210

Contact: Ayman Saad, MD

United States, Texas

M.D. Anderson Cancer Center; Recruiting

Houston, Texas, United States, 77030

Contact: Chitra Hosing, MD

United States, Washington

Be The Match Collection Center Seattle; Recruiting

Seattle, Washington, United States, 98101

Contact: Huy Pham, MD

Sponsors and Collaborators

Magenta Therapeutics, Inc.

National Marrow Donor Program

Investigators

• Study Chair: Steven Devine, MD; National Marrow Donor Program

More Information

• Responsible Party: Magenta Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT04762875
• Other Study ID Numbers: 145-ADS-202
• First Posted: February 21, 2021
• Last Update Posted: June 14, 2021
• Last Verified: May 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Neoplasms by Histologic Type; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Plerixafor octahydrochloride; Anti-HIV Agents; Anti-Retroviral Agents; Antiviral Agents; Anti-Infective Agents