Clinical trial NCT03248479: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Hematological Malignancies
Keywords: CD47
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2017-08-14
Enrollment: 258
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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) 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.

Key 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.

Primary outcomes:
measure: Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)
timeFrame: Up to 4 years
measure: Complete Remission (CR) Rate For Participants With AML
timeFrame: Up to 5 years
measure: CR Rate for Participants With MDS
timeFrame: Up to 5 years
measure: Percentage of Participants With Red Blood Cell (RBC) Transfusion Independence for Participants With Low-Risk MDS
timeFrame: Up to 8 weeks
Secondary outcomes:
measure: Serum Concentration for Magrolimab in TN/U AML and TN MDS Participants
timeFrame: Predose and/or after 1 hour of infusion (duration 3 hours (± 30 minutes) for 1mg/kg; 2 hours for 15 mg/kg, 30 mg/kg and 60 mg/kg) in Cycles (each cycle of 28 days) 1 to 7, 9, 11, 13, 15, on Days 1, 2, 3, 4, 8, 11, 15, 16, 17, 18, 22, EOT, Safety Follow-up
measure: Percentage of Participants Who Developed Anti-Magrolimab Antibodies
timeFrame: Up to 5 years
measure: Duration of Complete Remission (DCR) in Participants With AML and MDS
timeFrame: Up to 5 years
measure: Percentage of MDS Participants With Objective Response Rate (ORR) as Defined by IWG 2006 MDS Response Criteria
timeFrame: Up to 5 years
measure: Percentage of AML Participants With Objective Response Rate (ORR)
timeFrame: Up to 5 years
measure: Percentage of Participants With Complete Remission With Partial Hematologic Recovery (CRh) for AML Participants
timeFrame: Up to 5 years
measure: Duration of Response (DOR) for Participants With AML
timeFrame: Up to 5 years
measure: Duration of Response for Participants With MDS
timeFrame: Up to 5 years
measure: Overall Survival (OS) for Participants With AML or MDS
timeFrame: Up to 5 years
measure: Progression Free Survival (PFS) for Participants With AML or MDS
timeFrame: Up to 5 years
measure: Relapse Free Survival (RFS) for Participants With AML or MDS
timeFrame: Up to 5 years
measure: Event Free Survival (EFS) for Participants With AML or MDS
timeFrame: Up to 5 years
measure: Change From Baseline in Hemoglobin on Therapy
timeFrame: Baseline and Day 1
measure: 12-week RBC Transfusion Independence Rates
timeFrame: Up to 12 Weeks
measure: Minimal Residual Disease (MRD) Negative Response Rate
timeFrame: Up to 5 years
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: La Jolla
country: United States
facility: University of California San Diego (UCSD)
state: California
city: Los Angeles
country: United States
facility: UCLA Clinical and Translational Research Center (CTRC)
state: California
city: Orange
country: United States
facility: Chao Family Comprehensive Cancer Center - UC Irvine Medical Center
state: California
city: Sacramento
country: United States
facility: University of California Davis Comprehensive Cancer Center
state: California
city: Stanford
country: United States
facility: Stanford University Medical Center
state: California
city: Aurora
country: United States
facility: University of Colorado Cancer Center
state: Colorado
city: Miami
country: United States
facility: University Of Miami - Miller School Of Medicine, Sylvester Comprehensive Cancer Center
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center & Research Institute
state: Florida
city: Chicago
country: United States
facility: The University of Chicago
state: Illinois
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute/ Boston Children's Hospital
state: Massachusetts
city: Kansas City
country: United States
facility: Mid America Division, Inc.
state: Missouri
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: New York
country: United States
facility: Weill Cornell Medical College - New York-Presbyterian Hospital
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: New York
country: United States
facility: Herbert Irving Comprehensive Cancer Center-Columbia University Medical Center
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Columbus
country: United States
facility: Ohio State University Medical Center
state: Ohio
city: Oklahoma City
country: United States
facility: Stephenson Cancer Center
state: Oklahoma
city: Nashville
country: United States
facility: Tennesssee Oncology - Centennial Clinic Location
state: Tennessee
city: Dallas
country: United States
facility: Texas Oncology - Baylor Charles A. Simmons Cancer Center
state: Texas
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Milwaukee
country: United States
facility: Medical College of WI Froedtert Hospital
state: Wisconsin
city: Oxford
country: United Kingdom
facility: Oxford Centre for Respiratory Medicine Churchill Hospital, Oxford University Hospitals NHS Trust
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References:
citation: Daver NG, Vyas P, Kambhampati S, Al Malki MM, Larson RA, Asch AS, Mannis G, Chai-Ho W, Tanaka TN, Bradley TJ, Jeyakumar D, Wang ES, Sweet K, Kantarjian HM, Garcia-Manero G, Komrokji R, Xing G, Ramsingh G, Renard C, Zeidner JF, Sallman DA. Tolerability and Efficacy of the Anticluster of Differentiation 47 Antibody Magrolimab Combined With Azacitidine in Patients With Previously Untreated AML: Phase Ib Results. J Clin Oncol. 2023 Nov 1;41(31):4893-4904. doi: 10.1200/JCO.22.02604. Epub 2023 Sep 13.
citation: Sallman DA, Asch AS, Kambhampati S, et al. The first-in-class anti-CD47 antibody magrolimab combined with azacitidine is well tolerated and effective in AML patients: phase 1b results. American Society of Hematology (ASH); 2020 05-08 December. Annual Meeting Virtual.
citation: Sallman DA, Asch AS, Al Malki MM, et al. The first-in-class anti-CD47 antibody magrolimab (5F9) in combination with azacitidine is effective in MDS and AML patients: ongoing phase 1b results [Abstract]. American Society of Hematology (ASH); 2019 07-10 December. Orlando, FL.