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 Genders
All
Accepts Healthy Volunteers
No

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

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 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
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

More Details

Status
Terminated
Sponsor
Gilead Sciences

Study Contact