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

NCT ID: NCT03248479

Last Updated: 2025-01-17

Study Results

Results available

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1

Total Enrollment

258 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-09-08

Study Completion Date

2023-09-05

Brief Summary

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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

Detailed Description

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Conditions

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Hematological Malignancies

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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TN MDS Cohort Higher Risk QW 30 mg/kg

Participants who are treatment-naive (TN) with higher risk myelodysplastic syndrome (MDS) 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 Days 11, 15, 22, and then weekly (QW) starting Cycle 2 up to end of the study. Participants will receive azacitidine 75 mg/m\^2 on Days 1 to 7 of each cycle (each cycle was of 28 days). Maximum treatment duration was up to 4 years.

Group Type EXPERIMENTAL

Magrolimab

Intervention Type DRUG

Administered intravenously

Azacitidine

Intervention Type DRUG

Administered according to region-specific drug labeling either subcutaneously or intravenously

TN MDS Cohort Higher Risk Q2W 30 mg/kg

Participants who are TN with higher risk MDS 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 Days 11, 15, 22, and then weekly starting Cycle 2 and given every 2 weeks (Q2W) from Cycle 3 up to end of the study. Participants will receive azacitidine 75 mg/m\^2 on Days 1 to 7 of each cycle (each cycle was of 28 days). Maximum treatment duration was up to 4 years.

Group Type EXPERIMENTAL

Magrolimab

Intervention Type DRUG

Administered intravenously

Azacitidine

Intervention Type DRUG

Administered according to region-specific drug labeling either subcutaneously or intravenously

TN/U AML Cohort: Magrolimab + Azacitidine

Participants who are treatment-naive or unfit (TN/U) with acute myeloid leukemia (AML) 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 Days 11, 15, 22, and then QW starting Cycle 2 and then given QW and Q2W from Cycle 3 up to end of the study. Participants will receive azacitidine 75 mg/m\^2 on Days 1 to 7 of each cycle (each cycle was of 28 days). Maximum treatment duration was up to 4 years.

Group Type EXPERIMENTAL

Magrolimab

Intervention Type DRUG

Administered intravenously

Azacitidine

Intervention Type DRUG

Administered according to region-specific drug labeling either subcutaneously or intravenously

R/R AML Cohort: Magrolimab + Azacitidine

Participants with relapsed/refractory (r/r) AML will receive magrolimab 1 mg/kg for Cycle 1 Week 1 (Days 1, 4); 15 mg/kg on Cycle 1 Day 8, 30 mg/kg on Cycle 1 Days 11, 15 and 22 through end of Cycle 2 and then 30 mg/kg QW in Cycle 2 and then 30 mg/kg QW and Q2W starting Cycle 3 and thereafter (each cycle was of 28 days). Participants will receive azacitidine 75 mg/m\^2 on Days 1 to 7 of each cycle (each cycle was of 28 days). Maximum treatment duration was up to 4 years.

Group Type EXPERIMENTAL

Magrolimab

Intervention Type DRUG

Administered intravenously

Azacitidine

Intervention Type DRUG

Administered according to region-specific drug labeling either subcutaneously or intravenously

R/R AML Cohort: Magrolimab

Participants with r/r AML will receive magrolimab 1 mg/kg for Cycle 1 Week 1 (Days 1, Day 4); 15 mg/kg on Cycle 1 Day 8, 30 mg/kg on Cycle 1 Day 11 and Day 15, 30 mg/kg weekly on Cycle 1 Day 22 through end of Cycle 2, and 30 mg/kg Q2W starting Cycle 3 and thereafter (each cycle was of 28 days). Maximum treatment duration was up to 4 years.

Group Type EXPERIMENTAL

Magrolimab

Intervention Type DRUG

Administered intravenously

Rollover AML Cohort: Magrolimab

Participants may receive the same dose level and schedule (30 mg/kg) (i.e., twice weekly) of magrolimab monotherapy in each cycle (each cycle was of 28 days) as previously received on the Phase 1 AML study (SCI-CD47-002), or may transition to once-weekly dosing in this study at the discretion of the Investigator in each 28-day cycle and with Sponsor approval. Maximum treatment duration was up to 4 years.

Group Type EXPERIMENTAL

Magrolimab

Intervention Type DRUG

Administered intravenously

R/R MDS Cohort: Magrolimab + Azacitidine

Participants with r/r MDS will receive magrolimab 1 mg/kg for Cycle 1 Week 1 (Days 1, 4); 15 mg/kg on Cycle 1 Day 8, 30 mg/kg on Cycle 1 Days 11, 15 and 22 through end of Cycle 2 and then 30 mg/kg QW in Cycle 2 and then 30 mg/kg Q2W starting Cycle 3 and thereafter (each cycle was of 28 days). Participants will receive azacitidine 75 mg/m\^2 on Days 1 to 7 of each cycle (each cycle was of 28 days). Maximum treatment duration was up to 4 years.

Group Type EXPERIMENTAL

Magrolimab

Intervention Type DRUG

Administered intravenously

Azacitidine

Intervention Type DRUG

Administered according to region-specific drug labeling either subcutaneously or intravenously

R/R MDS Cohort: Magrolimab to Magrolimab + Azacitidine

Participants with r/r MDS will receive magrolimab 1 mg/kg for Cycle 1 Week 1 (Days 1, 4); 15 mg/kg on Cycle 1 Day 8, 30 mg/kg on Cycle 1 Days 11, 15 and 22 through end of Cycle 2 and then 30 mg/kg QW in Cycle 2 and then 30 mg/kg Q2W starting Cycle 3 and thereafter (each cycle was of 28 days). Participants will receive azacitidine 75 mg/m\^2 on Days 1 to 7 of each cycle (each cycle was of 28 days). Maximum treatment duration was up to 4 years.

Participants with r/r MDS who do not have an objective response with magrolimab at the first protocol response assessment can have azacitidine added to magrolimab for subsequent cycles.

Group Type EXPERIMENTAL

Magrolimab

Intervention Type DRUG

Administered intravenously

Azacitidine

Intervention Type DRUG

Administered according to region-specific drug labeling either subcutaneously or intravenously

R/R MDS Cohort: Magrolimab

Participants with r/r MDS will receive 1 mg/kg magrolimab on Cycle 1 Week 1 (Days 1, 4); 15 mg/kg on Cycle 1 Day 8; 30 mg/kg on Cycle 1 Days 11, 15, 22, through end of Cycle 2 and then 30 mg/kg QW in Cycle 2 and then 30 mg/kg Q2W starting Cycle 3 and thereafter (each cycle was of 28 days). Maximum treatment duration was up to 4 years.

Group Type EXPERIMENTAL

Magrolimab

Intervention Type DRUG

Administered intravenously

Low Risk MDS Cohort: Magrolimab + Azacitidine

Participants with low risk MDS will receive 1 mg/kg magrolimab on Cycle 1 Week 1 Day 1; 30 mg/kg on Cycle 1 Days 8, 15 and 22; 60 mg/kg on Day 1 of Cycle 2 and subsequent cycles (each cycle was of 28 days) (each cycle was of 28 days) up to the end of the study. Participants will receive azacitidine 75 mg/m\^2 on Days 1 to 5 of each cycle. For participants who could not tolerate 60 mg/kg dose, the dose of magrolimab was reduced to 45 mg/kg. Maximum treatment duration was up to 4 years.

Group Type EXPERIMENTAL

Magrolimab

Intervention Type DRUG

Administered intravenously

Azacitidine

Intervention Type DRUG

Administered according to region-specific drug labeling either subcutaneously or intravenously

Low Risk MDS Cohort: Magrolimab to Magrolimab + Azacitidine

Participants with low risk MDS will receive 1 mg/kg magrolimab on Cycle 1 Week 1 Day 1; 30 mg/kg on Cycle 1 Days 8, 15 and 22; 60 mg/kg on Day 1 of Cycle 2 and subsequent cycles (each cycle was of 28 days) (each cycle was of 28 days) up to the end of the study. Participants will receive azacitidine 75 mg/m\^2 on Days 1 to 5 of each cycle. For participants who could not tolerate 60 mg/kg dose, the dose of magrolimab was reduced to 45 mg/kg. Maximum treatment duration was up to 4 years.

Participants with r/r MDS who do not have an objective response with magrolimab at the first protocol response assessment can have azacitidine added to magrolimab for subsequent cycles.

Group Type EXPERIMENTAL

Magrolimab

Intervention Type DRUG

Administered intravenously

Azacitidine

Intervention Type DRUG

Administered according to region-specific drug labeling either subcutaneously or intravenously

Low Risk MDS Cohort: Magrolimab

Participants with low risk MDS will receive 1 mg/kg magrolimab on Cycle 1 Week 1 Day 1; 30 mg/kg on Cycle 1 Days 8, 15 and 22; 60 mg/kg on Day 1 of Cycle 2 and subsequent cycles (each cycle was of 28 days) (each cycle was of 28 days) up to the end of the study. Maximum treatment duration was up to 4 years.

Group Type EXPERIMENTAL

Magrolimab

Intervention Type DRUG

Administered intravenously

Interventions

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Magrolimab

Administered intravenously

Intervention Type DRUG

Azacitidine

Administered according to region-specific drug labeling either subcutaneously or intravenously

Intervention Type DRUG

Other Intervention Names

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Hu5F9-G4 VIDAZA

Eligibility Criteria

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Inclusion Criteria

* Meets the criteria below for the appropriate cohort:

* Relapsed/Refractory Cohorts: Pathologically confirmed relapsed or refractory (primary refractory and/or relapsed refractory) acute myeloid leukemia (AML) or confirmed intermediate, high, or very high risk myelodysplastic syndromes (MDS) that is relapsed, refractory or intolerant to conventional therapy.
* 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.
* 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.
* RBC transfusion dependent low risk MDS cohort: Transfusion-dependent MDS individuals who are very low or low risk by Revised International Prognostic Scoring System (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.

Exclusion Criteria

* Prior treatment with cluster of differentiation 47 (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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Gilead Sciences

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Gilead Study Director

Role: STUDY_DIRECTOR

Gilead Sciences

Locations

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City of Hope National Medical Center

Duarte, California, United States

Site Status

University of California San Diego (UCSD)

La Jolla, California, United States

Site Status

UCLA Clinical and Translational Research Center (CTRC)

Los Angeles, California, United States

Site Status

Chao Family Comprehensive Cancer Center - UC Irvine Medical Center

Orange, California, United States

Site Status

University of California Davis Comprehensive Cancer Center

Sacramento, California, United States

Site Status

Stanford University Medical Center

Stanford, California, United States

Site Status

University of Colorado Cancer Center

Aurora, Colorado, United States

Site Status

University Of Miami - Miller School Of Medicine, Sylvester Comprehensive Cancer Center

Miami, Florida, United States

Site Status

H. Lee Moffitt Cancer Center & Research Institute

Tampa, Florida, United States

Site Status

The University of Chicago

Chicago, Illinois, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Dana Farber Cancer Institute/ Boston Children's Hospital

Boston, Massachusetts, United States

Site Status

Mid America Division, Inc.

Kansas City, Missouri, United States

Site Status

Roswell Park Cancer Institute

Buffalo, New York, United States

Site Status

Weill Cornell Medical College - New York-Presbyterian Hospital

New York, New York, United States

Site Status

Icahn School of Medicine at Mount Sinai

New York, New York, United States

Site Status

Herbert Irving Comprehensive Cancer Center-Columbia University Medical Center

New York, New York, United States

Site Status

Montefiore Medical Center

The Bronx, New York, United States

Site Status

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Site Status

Duke University Medical Center

Durham, North Carolina, United States

Site Status

Ohio State University Medical Center

Columbus, Ohio, United States

Site Status

Stephenson Cancer Center

Oklahoma City, Oklahoma, United States

Site Status

Tennesssee Oncology - Centennial Clinic Location

Nashville, Tennessee, United States

Site Status

Texas Oncology - Baylor Charles A. Simmons Cancer Center

Dallas, Texas, United States

Site Status

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Medical College of WI Froedtert Hospital

Milwaukee, Wisconsin, United States

Site Status

Oxford Centre for Respiratory Medicine Churchill Hospital, Oxford University Hospitals NHS Trust

Oxford, , United Kingdom

Site Status

Countries

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United States United Kingdom

References

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Daver NG, Vyas P, Kambhampati S, Al Malki MM, Larson RA, Asch AS, Mannis G, Chai-Ho W, Tanaka TN, Bradley TJ, Jeyakumar D, Wang ES, Sweet K, Kantarjian HM, Garcia-Manero G, Komrokji R, Xing G, Ramsingh G, Renard C, Zeidner JF, Sallman DA. Tolerability and Efficacy of the Anticluster of Differentiation 47 Antibody Magrolimab Combined With Azacitidine in Patients With Previously Untreated AML: Phase Ib Results. J Clin Oncol. 2023 Nov 1;41(31):4893-4904. doi: 10.1200/JCO.22.02604. Epub 2023 Sep 13.

Reference Type BACKGROUND
PMID: 37703506 (View on PubMed)

Sallman DA, Asch AS, Kambhampati S, et al. The first-in-class anti-CD47 antibody magrolimab combined with azacitidine is well tolerated and effective in AML patients: phase 1b results. American Society of Hematology (ASH); 2020 05-08 December. Annual Meeting Virtual.

Reference Type BACKGROUND

Sallman DA, Asch AS, Al Malki MM, et al. The first-in-class anti-CD47 antibody magrolimab (5F9) in combination with azacitidine is effective in MDS and AML patients: ongoing phase 1b results [Abstract]. American Society of Hematology (ASH); 2019 07-10 December. Orlando, FL.

Reference Type BACKGROUND

Sallman DA, Al Malki MM, Asch AS, Wang ES, Jurcic JG, Bradley TJ, Flinn IW, Pollyea DA, Kambhampati S, Tanaka TN, Zeidner JF, Garcia-Manero G, Jeyakumar D, Komrokji R, Lancet J, Kantarjian HM, Gu L, Zhang Y, Tan A, Chao M, O'Hear C, Ramsingh G, Lal I, Vyas P, Daver NG. Magrolimab in Combination With Azacitidine in Patients With Higher-Risk Myelodysplastic Syndromes: Final Results of a Phase Ib Study. J Clin Oncol. 2023 May 20;41(15):2815-2826. doi: 10.1200/JCO.22.01794. Epub 2023 Mar 8.

Reference Type DERIVED
PMID: 36888930 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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Other Identifiers

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2017-000678-12

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

5F9005

Identifier Type: -

Identifier Source: org_study_id

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