Description:
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
Title
- Brief Title: Magrolimab Monotherapy or Magrolimab in Combination With Azacitidine in Participants With Hematological Malignancies
- Official Title: A Phase 1b Trial of Magrolimab Monotherapy or Magrolimab in Combination With Azacitidine in Patients With Hematological Malignancies
Clinical Trial IDs
- ORG STUDY ID:
5F9005
- SECONDARY ID:
2017-000678-12
- NCT ID:
NCT03248479
Conditions
- Hematological Malignancies
Interventions
| Drug | Synonyms | Arms |
|---|
| Magrolimab | Hu5F9-G4 | R/R Expansion Cohort: |
| Azacitidine | VIDAZA | R/R Expansion Cohort: |
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
Trial Arms
| Name | Type | Description | Interventions |
|---|
| R/R Safety Cohort | Experimental | 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. | |
| R/R Expansion Cohort: | Experimental | 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. | |
| R/R MDS Magrolimab Monotherapy Cohort | Experimental | 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. | |
| Treatment-naive Unfit (TNU) Dose Evaluation Cohort | Experimental | 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. | |
| Treatment-naive Unfit (TNU) Dose Expansion Cohort | Experimental | 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. | |
| RBC transfusion-dependent low-risk MDS, Safety Run-in Phase | Experimental | 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. | |
| RBC transfusion-dependent low-risk MDS, Expansion Phase | Experimental | 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. | |
| Rollover | Experimental | 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. | |
Eligibility Criteria
Key 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
Key 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.
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Percentage of Participant Experiencing Adverse Events |
| Time Frame: | First dose date up to 4 years |
| Safety Issue: | |
| Description: | The CR rate is the proportion of participants who achieved CR, as defined by the Investigator based on European Leukemia Net (ELN) AML recommendations. |
Secondary Outcome Measures
| Measure: | Serum Concentration for Magrolimab |
| Time Frame: | Up to 6 years |
| Safety Issue: | |
| Description: | R/R and TN/U Cohorts: Pre-magrolimab infusion: Cycle 1 Days 1, 8, 15 & 22, Cycle 2 Days 1 & 8, every other cycle beginning with Cycle 3-Cycle 13 Day 1, End of Treatment (EOT) (after last dose of magrolimab or within 7 days of EOT decision), Safety Follow up Visit (SFU) (30 days after last dose of magrolimab); 1 hour (± 15 minutes) post magrolimab infusion: Cycle 1 Days 1 & 8, Cycle 2 Day 1, every other cycle Cycle 3-Cycle 13 Day 1
RBC MDS Cohort: Pre-magrolimab infusion: Cycle 1 Days 1, 8 & 15, Cycle 2 Days 1 & 15, every other cycle Day 1 beginning with Cycle 3 through Cycle 7 and then every third cycle through Cycle 13 Day 1; EOT; SFU; 15 minutes (± 15 minutes) post magrolimab infusion: Cycle 2 Day 1
Cycle length is 28 days
Infusion Duration: 3 hours (± 30 minutes) for 1mg/kg; 2 hours for 15 mg/kg, 30 mg/kg and 60 mg/kg |
| Measure: | Percentage of Participants who Developed Anti-Magrolimab Antibodies |
| Time Frame: | Up to 6 years |
| Safety Issue: | |
| Description: | R/R, TN/U Expansion, R/R MDS Cohorts: Before study drug (magrolimab or azacitidine), within 72 hours for initial dose and within 24 hours for subsequent doses Cycle 1 Days 1 and 8, Cycle 2 Day 1, Cycle 3-13 every 2 cycles Day 1, EOT (after last dose or within 7 days of EOT decision), SFU (30 days after last dose of magrolimab)
RBC MDS Cohort: Before study drug (magrolimab or azacitidine), within 72 hours for initial dose and within 24 hours for subsequent doses Cycle 1 Days 1 and 8, Cycle 2 Day 1, beginning with Cycle 3 through Cycle 7 and then every third cycle through Cycle 13 Day 1, EOT, & SFU |
| Measure: | Percentage of AML Participants With Objective Response Based on ELN AML Recommendations |
| Time Frame: | Up to 6 years |
| Safety Issue: | |
| Description: | |
| Measure: | Percentage of AML Participants With Objective Response Based on IWG AML Response Criteria |
| Time Frame: | Up to 6 years |
| Safety Issue: | |
| Description: | |
| Measure: | Objective Response Rate (ORR) in MDS as Defined by IWG 2006 MDS Response Criteria |
| Time Frame: | Up to 6 years |
| Safety Issue: | |
| Description: | The ORR is the proportion of patients who reach CR (including morphologic CR, CRMRD-, cCR, and mCR), CRi, CRh, PR, marrow CR, or MLFS while on study. |
| Measure: | Duration of Response (DOR) for Participants with AML |
| Time Frame: | Up to 6 years |
| Safety Issue: | |
| Description: | The duration of response will be measured from the time measurement criteria are met for complete remission (CR) (including morphologic CR, complete remission without minimal residual disease (CRMRD-), cytogenetic complete remission (cCR), and molecular complete remission (mCR), incomplete blood count recovery (CRi), partial hematologic recovery (CRh), partial remission (PR), marrow CR, or morphologic leukemia-free state (MLFS), whichever is first recorded, until the first date that recurrent or progressive disease, or death within 8 weeks of the last response assessment with evidence of no disease magrolimab progression is objectively documented. |
| Measure: | Duration of Response for Participants with MDS |
| Time Frame: | Up to 6 years |
| Safety Issue: | |
| Description: | The DOR will be measured from the time measurement criteria are first met for objective response as assessed by IWG MDS criteria until the first date that recurrent disease or death within 8 weeks of the last response assessment with evidence of no disease recurrence is objectively documented. |
| Measure: | RBC Transfusion Independence (no RBC transfusions for at least an 8-week consecutive period) |
| Time Frame: | Up to 8 weeks |
| Safety Issue: | |
| Description: | |
| Measure: | 12-week RBC Transfusion Independence Rates |
| Time Frame: | Up to 12 Weeks |
| Safety Issue: | |
| Description: | RBC transfusion independence rate is defined by the lack of RBC transfusions for at least an 12 week consecutive period at any time after starting therapy. |
| Measure: | Mean Hemoglobin Increase on Therapy |
| Time Frame: | Up to 6 years |
| Safety Issue: | |
| Description: | |
| Measure: | Progression Free Survival (PFS) for Participants with AML or MDS |
| Time Frame: | Up to 6 years |
| Safety Issue: | |
| Description: | The length of PFS is defined as the time from the date of study treatment initiation until the date of documented disease progression or death from any cause, whichever occurs first. |
| Measure: | Relapse Free Survival (RFS) for Participants with AML or MDS |
| Time Frame: | Up to 6 years |
| Safety Issue: | |
| Description: | The length of RFS is defined from the first date of attaining a CR (including morphologic CR, CRMRD-, cCR, and mCR) until the date of AML relapse or death from any cause, whichever occurs first. |
| Measure: | Event Free Survival (EFS) for Participants with AML or MDS |
| Time Frame: | Up to 6 years |
| Safety Issue: | |
| Description: | The length of EFS is defined as the time from the date of study treatment initiation until the date of documented disease progression, death from any cause, or treatment failure (defined as permanent treatment discontinuation from any cause), whichever occurs first. |
| Measure: | Overall Survival (OS) for Participants with AML or MDS |
| Time Frame: | Up to 6 years |
| Safety Issue: | |
| Description: | The length of overall survival will be measured from the date of study treatment initiation until the date of death from any cause. |
| Measure: | Level of minimal residual disease (MRD) Negativity Using a Multiparameter Flow Cytometry-Based Assay for Participants on Treatment |
| Time Frame: | Up to 6 years |
| Safety Issue: | |
| Description: | |
| Measure: | Complete Remission with Partial Hematologic Recovery (CRh) |
| Time Frame: | Up to 6 years |
| Safety Issue: | |
| Description: | |
Details
| Phase: | Phase 1 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | Gilead Sciences |
Trial Keywords
Last Updated
July 19, 2021
