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

Sponsor

Gilead Sciences (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT03248479

Collaborator

(none)

258

Enrollment

Locations

Arms

88.8

Anticipated Duration (Months)

9.6

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Hematological Malignancies	Drug: Magrolimab Drug: Azacitidine	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

258 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 1b Trial of Magrolimab Monotherapy or Magrolimab in Combination With Azacitidine in Patients With Hematological Malignancies

Actual Study Start Date :

Sep 8, 2017

Anticipated Primary Completion Date :

Feb 1, 2025

Anticipated Study Completion Date :

Feb 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
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

Outcome Measures

Primary Outcome Measures

Percentage of Participant Experiencing Adverse Events [First dose date up to 4 years]
Complete Remission (CR) Rate For Participants With AML [Up to 4 years]
The CR rate is the proportion of participants who achieved CR, as defined by the Investigator based on European Leukemia Net (ELN) AML recommendations.
RBC Transfusion Independence Rate for Participants with Low-Risk MDS [Up to 8 weeks]
RBC transfusion independence rate is defined by the lack of RBC transfusions for at least an 8 week consecutive period at any time after starting therapy.
Complete Remission Rate for Participants with MDS [Up to 4 years]
The CR rate is the proportion of MDS participants who reach morphologic CR while on study per International Working Group (IWG) 2006 criteria
Duration of Complete Remission (DCR) in Participants with AML and MDS [Up to 4 years]
For AML participants: The DCR will be measured from the time measurement criteria are first met for CR (including morphologic CR, complete remission without minimal residual disease (CRMRD-), cytogenetic complete remission (cCR), and molecular complete remission (mCR) 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. For MDS participants: The DCR will be measured from the time measurement criteria are first met for CR 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

Secondary Outcome Measures

Serum Concentration for Magrolimab [Up to 6 years]
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
Percentage of Participants who Developed Anti-Magrolimab Antibodies [Up to 6 years]
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
Percentage of AML Participants With Objective Response Based on ELN AML Recommendations [Up to 6 years]
Percentage of AML Participants With Objective Response Based on IWG AML Response Criteria [Up to 6 years]
Objective Response Rate (ORR) in MDS as Defined by IWG 2006 MDS Response Criteria [Up to 6 years]
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.
Duration of Response (DOR) for Participants with AML [Up to 6 years]
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.
Duration of Response for Participants with MDS [Up to 6 years]
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.
RBC Transfusion Independence (no RBC transfusions for at least an 8-week consecutive period) [Up to 8 weeks]
12-week RBC Transfusion Independence Rates [Up to 12 Weeks]
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.
Mean Hemoglobin Increase on Therapy [Up to 6 years]
Progression Free Survival (PFS) for Participants with AML or MDS [Up to 6 years]
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.
Relapse Free Survival (RFS) for Participants with AML or MDS [Up to 6 years]
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.
Event Free Survival (EFS) for Participants with AML or MDS [Up to 6 years]
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.
Overall Survival (OS) for Participants with AML or MDS [Up to 6 years]
The length of overall survival will be measured from the date of study treatment initiation until the date of death from any cause.
Level of minimal residual disease (MRD) Negativity Using a Multiparameter Flow Cytometry-Based Assay for Participants on Treatment [Up to 6 years]
Complete Remission with Partial Hematologic Recovery (CRh) [Up to 6 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Key Inclusion Criteria:

Meets the criteria below for the appropriate cohort:

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
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 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope National Medical Center	Duarte	California	United States	91010
2	University of California San Diego (UCSD)	La Jolla	California	United States	92093
3	UCLA Clinical and Translational Research Center (CTRC)	Los Angeles	California	United States	90095
4	Chao Family Comprehensive Cancer Center - UC Irvine Medical Center	Orange	California	United States	92868
5	University of California Davis Comprehensive Cancer Center	Sacramento	California	United States	95817
6	Stanford University Medical Center	Stanford	California	United States	94305
7	University of Colorado Cancer Center	Aurora	Colorado	United States	80045
8	University Of Miami - Miller School Of Medicine, Sylvester Comprehensive Cancer Center	Miami	Florida	United States	33136
9	H. Lee Moffitt Cancer Center & Research Institute	Tampa	Florida	United States	33612
10	The University of Chicago	Chicago	Illinois	United States	60637
11	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
12	Dana Farber Cancer Institute/ Boston Children's Hospital	Boston	Massachusetts	United States	02215
13	Mid America Division, Inc.	Kansas City	Missouri	United States	64132
14	Montefiore Medical Center	Bronx	New York	United States	10467
15	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
16	Weill Cornell Medical College - New York-Presbyterian Hospital	New York	New York	United States	10021
17	Icahn School of Medicine at Mount Sinai	New York	New York	United States	10029
18	Herbert Irving Comprehensive Cancer Center-Columbia University Medical Center	New York	New York	United States	10032
19	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina	United States	27599
20	Duke University Medical Center	Durham	North Carolina	United States	27705
21	Ohio State University Medical Center	Columbus	Ohio	United States	43210
22	Stephenson Cancer Center	Oklahoma City	Oklahoma	United States	73104
23	Tennesssee Oncology - Centennial Clinic Location	Nashville	Tennessee	United States	37203
24	Texas Oncology - Baylor Charles A. Simmons Cancer Center	Dallas	Texas	United States	75246
25	The University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030
26	Medical College of WI Froedtert Hospital	Milwaukee	Wisconsin	United States	53226
27	Oxford Centre for Respiratory Medicine Churchill Hospital, Oxford University Hospitals NHS Trust	Oxford		United Kingdom	OX3 7LE