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

NCT05823480 | Withdrawn Phase 1 FDA Drug

• 3 other identifiers: 22618NCI-2023-02417P30CA033572
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Acute Myeloid Leukemia; Myelodysplastic Syndrome

Outcome Measures

Primary Outcomes (2)

• Incidence of dose-limiting toxicities

  Dose limiting toxicities (DLT) are defined as any of the following events that are attributed at least possibly due to study regimen and occur from start of magrolimab (day +1) to the end of the first cycle of magrolimab maintenance (day +85 +/-7): Death, grade 3-4 non-hematological toxicities per National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE 5.0), grade 4 hematological toxicities per NCI CTCAE 5.0 that last for more than 21 days. Will utilize the revised National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 for adverse events reporting.

  The evaluation period of DLT is from starting study regimen (day + 1) to the first observation of DLT, or the end of the first cycle of Magrolimab maintenance (day +85) with a grace period of ±7days, whichever comes first. (Each cycle is 28 days)

• Maximum tolerated dose (MTD) and recommended phase 2 dose (RPD) of magrolimab

  Will use the time-to-event Bayesian optimal interval (TITE-BOIN) design \[1\] to find the maximum tolerated dose/recommended phase 2 dose (MTD/RP2D).

  The evaluation period of DLT is from starting study regimen (day + 1) to the first observation of DLT, or the end of the first cycle of Magrolimab maintenance (day +85) with a grace period of ±7days, whichever comes first. (Each cycle is 28 days)

Secondary Outcomes (8)

• Overall survival

  Time period from start of protocol therapy to death regardless of cause, assessed up to 6 years

• Progression free survival

  Time from start of protocol therapy to relapse/progression, or death, whichever comes first, assessed up to 6 years

• Cumulative incidence of relapse/progression (CIR)

  Time of start of treatment to time of relapse/progression, assessed up to 6 years

• Cumulative incidence of on-relapse mortality (NRM)

  Time of start of treatment to non-disease related death, assessed up to 6 years

• Cumulative incidence of acute graft versus host disease (aGvHD) of grades 2-4 and 3-4

  Time of start of treatment to first documented/biopsy proven acute GVHD onset date, at 180 days post transplant

Study Arms (1)

Treatment (magrolimab, azacitidine)

EXPERIMENTAL

Patients undergo allo HCT per standard of care. Patients then receive magrolimab IV and azacitidine IV on study. Patients undergo ECHO or MUGA during screening and blood sample collection and bone marrow biopsy and aspirate throughout the study.

Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Drug: Azacitidine; Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspirate; Procedure: Bone Marrow Biopsy; Procedure: Echocardiography; Biological: Magrolimab; Procedure: Multigated Acquisition Scan; Other: Questionnaire Administration

Interventions

Allogeneic Hematopoietic Stem Cell Transplantation PROCEDURE

Undergo allo HCT per standard of care

Also known as: Allogeneic, Allogeneic Hematopoietic Cell Transplantation, Allogeneic Stem Cell Transplantation, HSC, HSCT, Stem Cell Transplantation, Allogeneic

Treatment (magrolimab, azacitidine)

Azacitidine DRUG

Given IV

Also known as: 5 AZC, 5-AC, 5-Azacytidine, 5-AZC, Azacytidine, Azacytidine, 5-, Ladakamycin, Mylosar, Onureg, U-18496, Vidaza

Treatment (magrolimab, azacitidine)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (magrolimab, azacitidine)

Bone Marrow Aspirate PROCEDURE

Undergo bone marrow biopsy and aspirate

Also known as: Human Bone Marrow Aspirate

Treatment (magrolimab, azacitidine)

Bone Marrow Biopsy PROCEDURE

Undergo bone marrow biopsy and aspirate

Also known as: Biopsy of Bone Marrow, Biopsy, Bone Marrow

Treatment (magrolimab, azacitidine)

Echocardiography PROCEDURE

Undergo ECHO

Also known as: EC

Treatment (magrolimab, azacitidine)

Magrolimab BIOLOGICAL

Given IV

Also known as: Hu5F9-G4

Treatment (magrolimab, azacitidine)

Multigated Acquisition Scan PROCEDURE

Undergo MUGA

Also known as: Blood Pool Scan, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, MUGA, MUGA Scan, Multi-Gated Acquisition Scan, Radionuclide Ventriculogram Scan, Radionuclide Ventriculography, RNVG, SYMA Scanning, Synchronized Multigated Acquisition Scanning

Treatment (magrolimab, azacitidine)

Questionnaire Administration OTHER

Ancillary studies

Treatment (magrolimab, azacitidine)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Documented informed consent of the patient and/or legally authorized representative (done within 30 days of HCT day 0).
• Agreement to allow the use of archival tissue from diagnostic tumor biopsies.
• If unavailable, exceptions may be granted with study principal investigator (PI) approval.
• Age: 18-75 years old.
• Eastern Cooperative Oncology Group =\< 2.
• Patients who are scheduled to undergo allogeneic HCT for AML with high-risk cytogenetics per European Leukemia Net (ELN) or MDS with International Prognostic Scoring System (IPSS) of intermediate 2 with poor risk cytogenetics or molecular markers. OR patients with MRD+ disease OR active disease with \< 10% blast at the time of HCT.
• Patients who are scheduled to undergo their first or second HCT with reduced intensity conditioning regimen (any reduced intensity conditioning regimen per institutional standards is allowed), and regardless of GVHD prophylactic regimen.
• Allogeneic transplant regardless of donor type (matched, mismatched, haploidentical, etc.) or graft source (bone marrow or mobilized peripheral blood stem cells) are included.
• Pre-HCT exposure to anti-CD47 of hypomethylating agent (HMA) is allowed if no progression on therapy has been documented.
• Absolute neutrophil count (ANC) \>= 1.5 (without the use of granulocyte-colony stimulating factor \[GCSF\] for last 2 weeks) (To be performed within 45 days prior to transplant unless otherwise stated).
• NOTE: Transfusion (Red blood cells \[RBC\] or platelet) to achieve the above-mentioned counts is allowed.
• Platelet count \>= 50K (To be performed within 45 days prior to transplant unless otherwise stated).
• NOTE: Transfusion (RBC or platelet) to achieve the above-mentioned counts is allowed.
• NOTE: Complete blood count (CBC) should be done within 2 weeks of day 1 of the protocol.
• Total bilirubin =\< 1.5 X upper limit of normal (ULN) (unless has Gilbert's disease) (To be performed within 45 days prior to transplant unless otherwise stated).

You may not qualify if:

• Patient who underwent more than 2 allogeneic HCTs.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agents (azacitidine or magrolimab).
• Females only: Pregnant or breastfeeding.
• Any other condition that would, in the Investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures.
• Known inherited or acquired bleeding disorders.
• Clinical suspicion of active central nervous system (CNS) involvement by MDS.
• Significant medical diseases or conditions, including but not limited to, acute myocardial infarction within the last 6 months, unstable angina, uncontrolled diabetes, significant active infection and congestive heart failure (CHF) New York Heart Association (NYHA) class 3-4.
• Known or active hepatitis B or C infection or human immunodeficiency virus (HIV) infection in medical history.
• Prospective patients who, in the opinion of the principal investigator (PI), may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics).

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes

Interventions

Stem Cell Transplantation; Azacitidine; Specimen Handling; Biopsy; magrolimab

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Cytodiagnosis; Cytological Techniques; Diagnostic Techniques, Surgical

Study Officials

• Monzr M Al Malki, MD

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 29, 2023
• First Posted: April 21, 2023
• Study Start: October 9, 2024
• Primary Completion: February 14, 2026
• Study Completion: February 14, 2026
• Last Updated: September 19, 2024

Record last verified: 2024-09