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Purpose

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

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

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

Study Design

Phase
Phase 1
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
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.
  • 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
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.
  • 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
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.
  • 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 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.
  • 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 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.
  • Drug: Magrolimab
    Administered intravenously
    Other names:
    • Hu5F9-G4
Experimental
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.
  • Drug: Magrolimab
    Administered intravenously
    Other names:
    • Hu5F9-G4
Experimental
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.
  • 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 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.
  • 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 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.
  • Drug: Magrolimab
    Administered intravenously
    Other names:
    • Hu5F9-G4
Experimental
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.
  • 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
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.
  • 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
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.
  • Drug: Magrolimab
    Administered intravenously
    Other names:
    • Hu5F9-G4

More Details

Status
Terminated
Sponsor
Gilead Sciences

Study Contact

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.