Magrolimab Monotherapy or Magrolimab in Combination With Azacitidine in Participants With Hematological Malignancies

A Phase 1b Trial of Magrolimab Monotherapy or Magrolimab in Combination With Azacitidine in Patients With Hematological Malignancies

The primary objectives of this study are:

• To confirm the safety and tolerability of magrolimab monotherapy in a relapsed/refractory (R/R) acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) population, and of magrolimab in combination with azacitidine in previously untreated participants with AML or MDS and participants with R/R AML and MDS
• To evaluate the efficacy of magrolimab monotherapy in R/R AML/MDS, and of magrolimab in combination with azacitidine in previously untreated participants with AML/MDS, or R/R AML/MDS as measured by complete remission (CR) rate for participants with AML and higher-risk MDS, and duration of complete response for participants with AML and higher-risk MDS, and duration of CR for participants with AML and higher-risk MDS
• To evaluate the safety, tolerability, and efficacy of magrolimab monotherapy or combination with azacitidine in low-risk MDS participants as measured by red blood cell (RBC) transfusion independence rate

Study Overview

• Status: Terminated
• Conditions: Hematological Malignancies
• Intervention / Treatment: Drug: Magrolimab; Drug: Azacitidine

• Study Type: Interventional
• Enrollment (Actual): 258
• Phase: Phase 1

Expanded Access

Temporarily not available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• United Kingdom
  • Oxford, United Kingdom, OX3 7LE
    • Oxford Centre for Respiratory Medicine Churchill Hospital, Oxford University Hospitals NHS Trust
• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope National Medical Center
    • La Jolla, California, United States, 92093
      • University of California San Diego (UCSD)
    • Los Angeles, California, United States, 90095
      • UCLA Clinical and Translational Research Center (CTRC)
    • Orange, California, United States, 92868
      • Chao Family Comprehensive Cancer Center - UC Irvine Medical Center
    • Sacramento, California, United States, 95817
      • University of California Davis Comprehensive Cancer Center
    • Stanford, California, United States, 94305
      • Stanford University Medical Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Cancer Center
  • Florida
    • Miami, Florida, United States, 33136
      • University Of Miami - Miller School Of Medicine, Sylvester Comprehensive Cancer Center
    • Tampa, Florida, United States, 33612
      • H. Lee Moffitt Cancer Center & Research Institute
  • Illinois
    • Chicago, Illinois, United States, 60637
      • The University Of Chicago
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute/ Boston Children's Hospital
  • Missouri
    • Kansas City, Missouri, United States, 64132
      • Mid America Division, Inc.
  • New York
    • Bronx, New York, United States, 10467
      • Montefiore Medical Center
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai
    • New York, New York, United States, 10021
      • Weill Cornell Medical College - New York-Presbyterian Hospital
    • New York, New York, United States, 10032
      • Herbert Irving Comprehensive Cancer Center-Columbia University Medical Center
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina at Chapel Hill
    • Durham, North Carolina, United States, 27705
      • Duke University Medical Center
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State University Medical Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Stephenson Cancer Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Tennesssee Oncology - Centennial Clinic Location
  • Texas
    • Dallas, Texas, United States, 75246
      • Texas Oncology - Baylor Charles A. Simmons Cancer Center
    • Houston, Texas, United States, 77030
      • The University of Texas MD Anderson Cancer Center
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of WI Froedtert Hospital

Participation Criteria

Eligibility Criteria

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

Description

Key Inclusion Criteria:

• Meets the criteria below for the appropriate cohort:

  1. Relapsed/Refractory Cohorts: Pathologically confirmed relapsed or refractory (primary refractory and/or relapsed refractory) AML or confirmed intermediate, high, or very high risk MDS that is relapsed, refractory or intolerant to conventional therapy
  2. Treatment-naive/ Unfit Cohorts: Previously untreated individuals with histological confirmation of AML who are ineligible for treatment with a standard cytarabine and anthracycline induction regimen; or previously untreated individuals with intermediate, high, or very high risk MDS. Prior and concurrent therapy with hydroxyurea, oral etoposide, erythroid and/or myeloid growth factors is allowed.
  3. Rollover Cohort: Individuals on active magrolimab therapy on the Phase 1 AML (SCI-CD47-002; NCT02678338) trial who are deriving clinical benefit by Investigator assessment
  4. RBC transfusion dependent low risk MDS cohort: Transfusion-dependent MDS individuals who are very low or low risk by IPSS-R with previous treatment with an erythroid stimulating agent or lenalidomide.
• White blood cell (WBC) count ≤ 20 x 10^3/mcL
• Adequate performance status and hematological, liver, and kidney function

Key Exclusion Criteria:

• Prior treatment with CD47 or signal regulatory protein alpha (SIRPα) targeting agents (with exception of magrolimab for individuals in the Rollover cohort).
• Treatment-naive/Unfit Cohorts Only: Any prior anti-leukemic therapy (excluding hydroxyurea or oral etoposide), prior treatment with hypomethylating agents and/or low dose cytarabine.
• Acute promyelocytic leukemia.
• Known inherited or acquired bleeding disorders.
• Previous allogeneic hematopoietic stem cell transplant within 6 months prior to enrollment, active graft versus host disease (GVHD), or requiring transplant-related immunosuppression.
• Clinical suspicion of active central nervous system (CNS) involvement by leukemia
• Known active or chronic hepatitis B or C infection or HIV
• Pregnancy or active breastfeeding

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: R/R Safety Cohort; Participants will receive 1 mg/kg magrolimab twice weekly for Cycle 1 Week 1 (Day 1 and 4); 15 mg/kg on Cycle 1 Day 8; 30 mg/kg on Cycle 1 Days 11 and 15; and 30 mg/kg weekly thereafter starting Cycle 3 up to end of the study.	Drug: Magrolimab; Administered intravenously; Other Names: Hu5F9-G4
Experimental: R/R Expansion Cohort: Participants will receive 1 mg/kg magrolimab twice weekly for Cycle 1 Week 1 (Day 1 and Day 4); 15 mg/kg on Cycle 1 Day 8; 30 mg/kg on Cycle 1 Days 11 and 15; 30 mg/kg weekly on Cycle 1 Day 22 through end of Cycle 2, then 30 mg/kg every 2 weeks starting Cycle 3 up to end of the study + azacitidine 75 mg/m^2 on Days 1 to 7 of each cycle.	Drug: Magrolimab; Administered intravenously; Other Names: Hu5F9-G4; Drug: Azacitidine; Administered according to region-specific drug labeling either subcutaneously or intravenously; Other Names: VIDAZA
Experimental: R/R MDS Magrolimab Monotherapy Cohort; Participants will receive 1 mg/kg magrolimab on Cycle 1 (Days 1, 4); 15 mg/kg on Cycle 1 Day 8; 30 mg/kg on Cycle 1 Day 11, 15, 22, weekly on Cycle 2, and then biweekly starting Cycle 3 up to end of the study.	Drug: Magrolimab; Administered intravenously; Other Names: Hu5F9-G4
Experimental: Treatment-naive Unfit (TNU) Dose Evaluation Cohort; Participants will receive 1 mg/kg magrolimab on Cycle 1 (Days 1, 4); 15 mg/kg on Cycle 1 Day 8; 30 mg/kg on Cycle 1 Day 11, 15, 22, and then weekly starting Cycle 2 up to end of the study + azacitidine 75 mg/m^2 on Days 1 to 7 of each cycle.	Drug: Magrolimab; Administered intravenously; Other Names: Hu5F9-G4; Drug: Azacitidine; Administered according to region-specific drug labeling either subcutaneously or intravenously; Other Names: VIDAZA
Experimental: Treatment-naive Unfit (TNU) Dose Expansion Cohort; Participants will receive 1 mg/kg magrolimab twice weekly for Cycle 1; 15 mg/kg weekly for Cycle 1 Day 8; 30 mg/kg weekly through end of cycle 2; and then 30 mg/kg every 2 weeks starting Cycle 3 up to end of the study + azacitidine 75 mg/m^2 on Days 1 to 7 of each cycle.	Drug: Magrolimab; Administered intravenously; Other Names: Hu5F9-G4; Drug: Azacitidine; Administered according to region-specific drug labeling either subcutaneously or intravenously; Other Names: VIDAZA
Experimental: RBC transfusion-dependent low-risk MDS, Safety Run-in Phase; Participants will receive 1 mg/kg magrolimab on Cycle 1 Day 1; 30 mg/kg on Cycle 1 Days 8, 15, and 22; and 60 mg/kg every 4 weeks starting on Cycle 2 Day 1 and thereafter up to end of the study. For participants who do not respond after Cycle 2, azacitidine 75 mg/m^2 may be added on subsequent cycles (ie starting at Cycle 3) on Days 1 to 5 of each cycle.	Drug: Magrolimab; Administered intravenously; Other Names: Hu5F9-G4; Drug: Azacitidine; Administered according to region-specific drug labeling either subcutaneously or intravenously; Other Names: VIDAZA
Experimental: RBC transfusion-dependent low-risk MDS, Expansion Phase; Participants will receive 1 mg/kg magrolimab on Cycle 1 Day 1; at 30 mg/kg on Cycle 1 Days 8, 15, and 22; and 60 mg/kg every 4 starting on Cycle 2 Day 1 and thereafter up to end of the study + azacitidine 75 mg/m^2 on Days 1 to 5 of each cycle.	Drug: Magrolimab; Administered intravenously; Other Names: Hu5F9-G4; Drug: Azacitidine; Administered according to region-specific drug labeling either subcutaneously or intravenously; Other Names: VIDAZA
Experimental: Rollover; Participants on a previous AML Phase 1 trial (SCI-CD47-002; NCT02678338) with clinical benefit on magrolimab treatment will receive the same dose level (0.1 mg/kg up to 30.0mg/kg based on the cohort to which the participant was assigned) twice weekly or may transition to once weekly dosing at the discretion of the Investigator and approval from Gilead.	Drug: Magrolimab; Administered intravenously; Other Names: Hu5F9-G4

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participant Experiencing Adverse Events		First dose date up to 4 years
Complete Remission (CR) Rate For Participants With AML	The CR rate is the proportion of participants who achieved CR, as defined by the Investigator based on European Leukemia Net (ELN) AML recommendations.	Up to 4 years
RBC Transfusion Independence Rate for Participants with Low-Risk MDS	RBC transfusion independence rate is defined by the lack of RBC transfusions for at least an 8 week consecutive period at any time after starting therapy.	Up to 8 weeks
Complete Remission Rate for Participants with MDS	The CR rate is the proportion of MDS participants who reach morphologic CR while on study per International Working Group (IWG) 2006 criteria	Up to 4 years
Duration of Complete Remission (DCR) in Participants with AML and MDS	For AML participants: The DCR will be measured from the time measurement criteria are first met for CR (including morphologic CR, complete remission without minimal residual disease (CRMRD-), cytogenetic complete remission (cCR), and molecular complete remission (mCR) until the first date that recurrent disease or death within 8 weeks of the last response assessment with evidence of no disease recurrence is objectively documented. For MDS participants: The DCR will be measured from the time measurement criteria are first met for CR until the first date that recurrent disease or death within 8 weeks of the last response assessment with evidence of no disease recurrence is objectively documented	Up to 4 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum Concentration for Magrolimab	R/R and TN/U Cohorts: Pre-magrolimab infusion: Cycle 1 Days 1, 8, 15 & 22, Cycle 2 Days 1 & 8, every other cycle beginning with Cycle 3-Cycle 13 Day 1, End of Treatment (EOT) (after last dose of magrolimab or within 7 days of EOT decision), Safety Follow up Visit (SFU) (30 days after last dose of magrolimab); 1 hour (± 15 minutes) post magrolimab infusion: Cycle 1 Days 1 & 8, Cycle 2 Day 1, every other cycle Cycle 3-Cycle 13 Day 1; RBC MDS Cohort: Pre-magrolimab infusion: Cycle 1 Days 1, 8 & 15, Cycle 2 Days 1 & 15, every other cycle Day 1 beginning with Cycle 3 through Cycle 7 and then every third cycle through Cycle 13 Day 1; EOT; SFU; 15 minutes (± 15 minutes) post magrolimab infusion: Cycle 2 Day 1; Cycle length is 28 days; Infusion Duration: 3 hours (± 30 minutes) for 1mg/kg; 2 hours for 15 mg/kg, 30 mg/kg and 60 mg/kg	Up to 6 years
Percentage of Participants who Developed Anti-Magrolimab Antibodies	R/R, TN/U Expansion, R/R MDS Cohorts: Before study drug (magrolimab or azacitidine), within 72 hours for initial dose and within 24 hours for subsequent doses Cycle 1 Days 1 and 8, Cycle 2 Day 1, Cycle 3-13 every 2 cycles Day 1, EOT (after last dose or within 7 days of EOT decision), SFU (30 days after last dose of magrolimab) RBC MDS Cohort: Before study drug (magrolimab or azacitidine), within 72 hours for initial dose and within 24 hours for subsequent doses Cycle 1 Days 1 and 8, Cycle 2 Day 1, beginning with Cycle 3 through Cycle 7 and then every third cycle through Cycle 13 Day 1, EOT, & SFU	Up to 6 years
Percentage of AML Participants With Objective Response Based on ELN AML Recommendations		Up to 6 years
Percentage of AML Participants With Objective Response Based on IWG AML Response Criteria		Up to 6 years
Objective Response Rate (ORR) in MDS as Defined by IWG 2006 MDS Response Criteria	The ORR is the proportion of patients who reach CR (including morphologic CR, CRMRD-, cCR, and mCR), CRi, CRh, PR, marrow CR, or MLFS while on study.	Up to 6 years
Duration of Response (DOR) for Participants with AML	The duration of response will be measured from the time measurement criteria are met for complete remission (CR) (including morphologic CR, complete remission without minimal residual disease (CRMRD-), cytogenetic complete remission (cCR), and molecular complete remission (mCR), incomplete blood count recovery (CRi), partial hematologic recovery (CRh), partial remission (PR), marrow CR, or morphologic leukemia-free state (MLFS), whichever is first recorded, until the first date that recurrent or progressive disease, or death within 8 weeks of the last response assessment with evidence of no disease magrolimab progression is objectively documented.	Up to 6 years
Duration of Response for Participants with MDS	The DOR will be measured from the time measurement criteria are first met for objective response as assessed by IWG MDS criteria until the first date that recurrent disease or death within 8 weeks of the last response assessment with evidence of no disease recurrence is objectively documented.	Up to 6 years
RBC Transfusion Independence (no RBC transfusions for at least an 8-week consecutive period)		Up to 8 weeks
12-week RBC Transfusion Independence Rates	RBC transfusion independence rate is defined by the lack of RBC transfusions for at least an 12 week consecutive period at any time after starting therapy.	Up to 12 Weeks
Mean Hemoglobin Increase on Therapy		Up to 6 years
Progression Free Survival (PFS) for Participants with AML or MDS	The length of PFS is defined as the time from the date of study treatment initiation until the date of documented disease progression or death from any cause, whichever occurs first.	Up to 6 years
Relapse Free Survival (RFS) for Participants with AML or MDS	The length of RFS is defined from the first date of attaining a CR (including morphologic CR, CRMRD-, cCR, and mCR) until the date of AML relapse or death from any cause, whichever occurs first.	Up to 6 years
Event Free Survival (EFS) for Participants with AML or MDS	The length of EFS is defined as the time from the date of study treatment initiation until the date of documented disease progression, death from any cause, or treatment failure (defined as permanent treatment discontinuation from any cause), whichever occurs first.	Up to 6 years
Overall Survival (OS) for Participants with AML or MDS	The length of overall survival will be measured from the date of study treatment initiation until the date of death from any cause.	Up to 6 years
Level of minimal residual disease (MRD) Negativity Using a Multiparameter Flow Cytometry-Based Assay for Participants on Treatment		Up to 6 years
Complete Remission with Partial Hematologic Recovery (CRh)		Up to 6 years

Collaborators and Investigators

• Sponsor: Gilead Sciences
• Investigators: Study Director: Gilead Study Director, Gilead Sciences

Publications and helpful links

Helpful Links

• Gilead Clinical Trials Website

Study record dates

Study Major Dates

• Study Start (Actual): September 8, 2017
• Primary Completion (Actual): September 5, 2023
• Study Completion (Actual): September 5, 2023

Study Registration Dates

• First Submitted: August 10, 2017
• First Submitted That Met QC Criteria: August 10, 2017
• First Posted (Actual): August 14, 2017

Study Record Updates

• Last Update Posted (Actual): October 3, 2023
• Last Update Submitted That Met QC Criteria: September 29, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: CD47
• Additional Relevant MeSH Terms: Neoplasms by Site; Hematologic Diseases; Neoplasms; Hematologic Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Antineoplastic Agents, Immunological; Azacitidine; Magrolimab
• Other Study ID Numbers: 5F9005; 2017-000678-12 (EudraCT Number)

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
• product manufactured in and exported from the U.S.: No