NCT05823480

Magrolimab in Combination with Azacitidine After Allogeneic HCTin Treating Patients with High-Risk AML or MDS

A Multi-Center, Phase 1 Trial of Combining Anti-CD47 Antibody (Magrolimab) with Azacitidine As Post-Transplant Maintenance Therapy in Patients Who Underwent Allogeneic Hematopoietic Cell Transplantation for Treatment of High-Risk AML or MDS

• Status: Withdrawn
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: City of Hope Medical Center · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial studies how well the combination of magrolimab works with azacitidine after a donor stem cell transplant (allogeneic hematopoietic cell transplantation) in treating patients with high-risk acute myeloid leukemia or myelodysplastic syndrome. Magrolimab is a type of protein called an antibody. It is designed to target and block a protein called CD47. CD47 is present on cancer cells and is used by cancer cells to protect themselves from the body's immune system. Blocking CD47 with magrolimab may enable the body's immune system to find and destroy the cancer cells. Azacitidine is a chemotherapy drug that may prevent the return of acute myeloid leukemia or myelodysplastic syndrome by working in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Combining magrolimab and azacitidine may kill more cancer cells after allogeneic hematopoietic cell transplantation in patients with high-risk acute myeloid leukemia or myelodysplastic syndromes.

Detailed description

PRIMARY OBJECTIVE: I. Establish safety/feasibility and determine the recommended phase 2 dose (RP2D) of magrolimab in combination with a fixed dose of azacitidine when given as the maintenance therapy after reduced intensity conditioning allogeneic hematopoietic cell transplantation (HCT), in patients with high-risk acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). SECONDARY OBJECTIVES: I. Estimate overall survival (OS), progression-free survival (PFS), cumulative incidence (CI) of relapse/progression, non-relapse mortality (NRM) at +100 days and 1-year post- maintenance therapy. II. Estimate CI of acute graft-versus-host disease (GVHD) at 180 days post HCT, and chronic GVHD at one-year post-HCT. III. Longitudinally characterize minimal residual disease (MRD+) status in patients receiving maintenance therapy. IV. Feasibility of receiving magrolimab in combination with azacitidine as maintenance therapy in this patient population. EXPLORATORY OBJECTIVES: I. Characterize the presence and level of GVHD biomarkers and inflammatory cytokines in the first 100 days from the start of maintenance therapy. II. Assess the possible correlation between chimerism kinetics by AlloHeme assay (per next generation sequencing \[NGS\] assay) and post-HCT relapse. III. Describe kinetics of immune cell recovery and macrophage activation in the first-year post-HCT. IV. Assess health related quality of life (QoL) and symptoms on days 1, 60, 90 and 180 after starting maintenance therapy. OUTLINE: This is a dose-escalation study of magrolimab (MRD- patients only), followed by a dose-expansion study (MRD- and MRD+ patients). Patients undergo allo HCT per standard of care. Patients then receive magrolimab intravenously (IV) and azacitidine IV on study. Patients undergo echocardiogram (ECHO) or multi-gated acquisition scan (MUGA) during screening and blood sample collection and bone marrow biopsy and aspirate throughout the study.

Conditions

• Acute Myeloid Leukemia
• Myelodysplastic Syndrome

Interventions

Type	Name	Description
PROCEDURE	Allogeneic Hematopoietic Stem Cell Transplantation	Undergo allo HCT per standard of care
DRUG	Azacitidine	Given IV
PROCEDURE	Biospecimen Collection	Undergo blood sample collection
PROCEDURE	Bone Marrow Aspirate	Undergo bone marrow biopsy and aspirate
PROCEDURE	Bone Marrow Biopsy	Undergo bone marrow biopsy and aspirate
PROCEDURE	Echocardiography	Undergo ECHO
BIOLOGICAL	Magrolimab	Given IV
PROCEDURE	Multigated Acquisition Scan	Undergo MUGA
OTHER	Questionnaire Administration	Ancillary studies

Timeline

• Start date: 2024-10-09
• Primary completion: 2026-02-14
• Completion: 2026-02-14
• First posted: 2023-04-21
• Last updated: 2024-09-19

Regulatory

• FDA-regulated drug study