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

NCT03248479 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: 5F90052017-000678-12
• Study Type: interventional
• Target: 258
• Locations: 2 countries
• Sites: 27

Brief Summary

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

Conditions

Hematological Malignancies

Keywords

CD47

Outcome Measures

Primary Outcomes (4)

• Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)

  TEAEs were defined as any AEs with an onset date on or after the study drug start date and no later than 30 days after permanent discontinuation of study drug and before the first date of new anti-cancer therapy including stem-cell transplant (SCT) and/or any AEs leading to premature discontinuation of study drug.

  Up to 4 years

• Complete Remission (CR) Rate For Participants With AML

  The CR rate is the percentage of participants who achieved CR without minimal residual disease (CRMRD-), and CR as per European Leukemia Net (ELN) AML recommendations. CRMRD- per ELN was defined as neutrophils ≥1.0 × 10\^9/L; platelets ≥100 × 10\^9/L and \<5% bone marrow blasts. If studied pretreatment, CR with negativity for a genetic marker by real-time quantitative polymerase chain reaction (RT-qPCR) or similar modality or CR with negativity by multi-color flow cytometry. CR per ELN criteria is defined as neutrophils ≥1.0 × 10\^9/L; platelets ≥100 × 10\^9/L and \<5% bone marrow blasts. Absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease; MRD positive or unknown.

  Up to 5 years

• CR Rate for Participants With MDS

  The CR rate was the percentage of MDS participants who achieved CR per International Working Group (IWG) 2006 criteria. CR per IWG criteria is defined as bone marrow ≤5% myeloblasts with normal maturation of all cell lines. Persistent dysplasia will be noted. Peripheral blood should have: Hemoglobin (Hgb) ≥11 g/dL, platelets ≥100 × 10\^9/L, neutrophils ≥1.0 × 10\^9/L and blasts 0%.

  Up to 5 years

• Percentage of Participants With Red Blood Cell (RBC) Transfusion Independence for Participants With Low-Risk MDS

  RBC transfusion independence was 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

Secondary Outcomes (15)

• Serum Concentration for Magrolimab in TN/U AML and TN MDS Participants

  Predose and/or after 1 hour of infusion (duration 3 hours (± 30 minutes) for 1mg/kg; 2 hours for 15 mg/kg, 30 mg/kg and 60 mg/kg) in Cycles (each cycle of 28 days) 1 to 7, 9, 11, 13, 15, on Days 1, 2, 3, 4, 8, 11, 15, 16, 17, 18, 22, EOT, Safety Follow-up

• Percentage of Participants Who Developed Anti-Magrolimab Antibodies

  Up to 5 years

• Duration of Complete Remission (DCR) in Participants With AML and MDS

  Up to 5 years

• Percentage of MDS Participants With Objective Response Rate (ORR) as Defined by IWG 2006 MDS Response Criteria

  Up to 5 years

• Percentage of AML Participants With Objective Response Rate (ORR)

  Up to 5 years

Study Arms (12)

TN MDS Cohort Higher Risk QW 30 mg/kg

EXPERIMENTAL

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.

Drug: Magrolimab; Drug: Azacitidine

TN MDS Cohort Higher Risk Q2W 30 mg/kg

EXPERIMENTAL

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.

Drug: Magrolimab; Drug: Azacitidine

TN/U AML Cohort: Magrolimab + Azacitidine

EXPERIMENTAL

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.

Drug: Magrolimab; Drug: Azacitidine

R/R AML Cohort: Magrolimab + Azacitidine

EXPERIMENTAL

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.

Drug: Magrolimab; Drug: Azacitidine

R/R AML Cohort: Magrolimab

EXPERIMENTAL

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.

Drug: Magrolimab

Rollover AML Cohort: Magrolimab

EXPERIMENTAL

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.

Drug: Magrolimab

R/R MDS Cohort: Magrolimab + Azacitidine

EXPERIMENTAL

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.

Drug: Magrolimab; Drug: Azacitidine

R/R MDS Cohort: Magrolimab to Magrolimab + Azacitidine

EXPERIMENTAL

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.

Drug: Magrolimab; Drug: Azacitidine

R/R MDS Cohort: Magrolimab

EXPERIMENTAL

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.

Drug: Magrolimab

Low Risk MDS Cohort: Magrolimab + Azacitidine

EXPERIMENTAL

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.

Drug: Magrolimab; Drug: Azacitidine

Low Risk MDS Cohort: Magrolimab to Magrolimab + Azacitidine

EXPERIMENTAL

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.

Drug: Magrolimab; Drug: Azacitidine

Low Risk MDS Cohort: Magrolimab

EXPERIMENTAL

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.

Drug: Magrolimab

Interventions

Magrolimab DRUG

Administered intravenously

Also known as: Hu5F9-G4

Low Risk MDS Cohort: Magrolimab; Low Risk MDS Cohort: Magrolimab + Azacitidine; Low Risk MDS Cohort: Magrolimab to Magrolimab + Azacitidine; R/R AML Cohort: Magrolimab; R/R AML Cohort: Magrolimab + Azacitidine; R/R MDS Cohort: Magrolimab; R/R MDS Cohort: Magrolimab + Azacitidine; R/R MDS Cohort: Magrolimab to Magrolimab + Azacitidine; Rollover AML Cohort: Magrolimab; TN MDS Cohort Higher Risk Q2W 30 mg/kg; TN MDS Cohort Higher Risk QW 30 mg/kg; TN/U AML Cohort: Magrolimab + Azacitidine

Azacitidine DRUG

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

Also known as: VIDAZA

Low Risk MDS Cohort: Magrolimab + Azacitidine; Low Risk MDS Cohort: Magrolimab to Magrolimab + Azacitidine; R/R AML Cohort: Magrolimab + Azacitidine; R/R MDS Cohort: Magrolimab + Azacitidine; R/R MDS Cohort: Magrolimab to Magrolimab + Azacitidine; TN MDS Cohort Higher Risk Q2W 30 mg/kg; TN MDS Cohort Higher Risk QW 30 mg/kg; TN/U AML Cohort: Magrolimab + Azacitidine

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (27)

City of Hope National Medical Center

Duarte, California, 91010, United States

Location

University of California San Diego (UCSD)

La Jolla, California, 92093, United States

Location

UCLA Clinical and Translational Research Center (CTRC)

Los Angeles, California, 90095, United States

Location

Chao Family Comprehensive Cancer Center - UC Irvine Medical Center

Orange, California, 92868, United States

Location

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

Stanford University Medical Center

Stanford, California, 94305, United States

Location

University of Colorado Cancer Center

Aurora, Colorado, 80045, United States

Location

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

Miami, Florida, 33136, United States

Location

H. Lee Moffitt Cancer Center & Research Institute

Tampa, Florida, 33612, United States

Location

The University of Chicago

Chicago, Illinois, 60637, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana Farber Cancer Institute/ Boston Children's Hospital

Boston, Massachusetts, 02215, United States

Location

Mid America Division, Inc.

Kansas City, Missouri, 64132, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Weill Cornell Medical College - New York-Presbyterian Hospital

New York, New York, 10021, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Herbert Irving Comprehensive Cancer Center-Columbia University Medical Center

New York, New York, 10032, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Duke University Medical Center

Durham, North Carolina, 27705, United States

Location

Ohio State University Medical Center

Columbus, Ohio, 43210, United States

Location

Stephenson Cancer Center

Oklahoma City, Oklahoma, 73104, United States

Location

Tennesssee Oncology - Centennial Clinic Location

Nashville, Tennessee, 37203, United States

Location

Texas Oncology - Baylor Charles A. Simmons Cancer Center

Dallas, Texas, 75246, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Medical College of WI Froedtert Hospital

Milwaukee, Wisconsin, 53226, United States

Location

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

Oxford, OX3 7LE, United Kingdom

Location

Related Publications (4)

• 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.

  PMID: 37703506 BACKGROUND

• 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.

  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.

  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.

  PMID: 36888930 DERIVED

Related Links

• Gilead Clinical Trials Website

MeSH Terms

Conditions

Hematologic Neoplasms

Interventions

magrolimab; Azacitidine

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Results Point of Contact

• Title: Gilead Clinical Study Information Center
• Organization: Gilead Sciences

GileadClinicalTrials@gilead.com

1-833-445-3230 (GILEAD-0)

Study Officials

• Gilead Study Director

  Gilead Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: August 10, 2017
• First Posted: August 14, 2017
• Study Start: September 8, 2017
• Primary Completion: September 5, 2023
• Study Completion: September 5, 2023
• Last Updated: January 17, 2025
• Results First Posted: January 17, 2025

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1); US (26)