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

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

  • Hematological Malignancies

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