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

Hematological Malignancies Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03248479
• Other study ID #: 5F9005
• Secondary ID: 2017-000678-12
• Status: Terminated
• Phase: Phase 1
• Start date: September 8, 2017
• Est. completion date: September 5, 2023

Study information

• Verified date: September 2023
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 258
• Est. completion date: September 5, 2023
• Est. primary completion date: September 5, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 (SIRPa) 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.

Related Conditions & MeSH terms

• Hematologic Neoplasms
• Hematological Malignancies
• Neoplasms

Intervention

Drug:
• Magrolimab
Administered intravenously
• Azacitidine
Administered according to region-specific drug labeling either subcutaneously or intravenously

Locations

Country	Name	City	State
United Kingdom	Oxford Centre for Respiratory Medicine Churchill Hospital, Oxford University Hospitals NHS Trust	Oxford
United States	University of Colorado Cancer Center	Aurora	Colorado
United States	Dana Farber Cancer Institute/ Boston Children's Hospital	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Montefiore Medical Center	Bronx	New York
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	The University of Chicago	Chicago	Illinois
United States	Ohio State University Medical Center	Columbus	Ohio
United States	Texas Oncology - Baylor Charles A. Simmons Cancer Center	Dallas	Texas
United States	City of Hope National Medical Center	Duarte	California
United States	Duke University Medical Center	Durham	North Carolina
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Mid America Division, Inc.	Kansas City	Missouri
United States	University of California San Diego (UCSD)	La Jolla	California
United States	UCLA Clinical and Translational Research Center (CTRC)	Los Angeles	California
United States	University Of Miami - Miller School Of Medicine, Sylvester Comprehensive Cancer Center	Miami	Florida
United States	Medical College of WI Froedtert Hospital	Milwaukee	Wisconsin
United States	Tennesssee Oncology - Centennial Clinic Location	Nashville	Tennessee
United States	Herbert Irving Comprehensive Cancer Center-Columbia University Medical Center	New York	New York
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	Weill Cornell Medical College - New York-Presbyterian Hospital	New York	New York
United States	Stephenson Cancer Center	Oklahoma City	Oklahoma
United States	Chao Family Comprehensive Cancer Center - UC Irvine Medical Center	Orange	California
United States	University of California Davis Comprehensive Cancer Center	Sacramento	California
United States	Stanford University Medical Center	Stanford	California
United States	H. Lee Moffitt Cancer Center & Research Institute	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participant Experiencing Adverse Events		First dose date up to 4 years
Primary	Complete Remission (CR) Rate For Participants With AML	The CR rate is the proportion of participants who achieved CR, as defined by the Investigator based on European Leukemia Net (ELN) AML recommendations.	Up to 4 years
Primary	RBC Transfusion Independence Rate for Participants with Low-Risk MDS	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.	Up to 8 weeks
Primary	Complete Remission Rate for Participants with MDS	The CR rate is the proportion of MDS participants who reach morphologic CR while on study per International Working Group (IWG) 2006 criteria	Up to 4 years
Primary	Duration of Complete Remission (DCR) in Participants with AML and MDS	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	Up to 4 years
Secondary	Serum Concentration for Magrolimab	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	Up to 6 years
Secondary	Percentage of Participants who Developed Anti-Magrolimab Antibodies	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	Up to 6 years
Secondary	Percentage of AML Participants With Objective Response Based on ELN AML Recommendations		Up to 6 years
Secondary	Percentage of AML Participants With Objective Response Based on IWG AML Response Criteria		Up to 6 years
Secondary	Objective Response Rate (ORR) in MDS as Defined by IWG 2006 MDS Response Criteria	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.	Up to 6 years
Secondary	Duration of Response (DOR) for Participants with AML	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.	Up to 6 years
Secondary	Duration of Response for Participants with MDS	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.	Up to 6 years
Secondary	RBC Transfusion Independence (no RBC transfusions for at least an 8-week consecutive period)		Up to 8 weeks
Secondary	12-week RBC Transfusion Independence Rates	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.	Up to 12 Weeks
Secondary	Mean Hemoglobin Increase on Therapy		Up to 6 years
Secondary	Progression Free Survival (PFS) for Participants with AML or MDS	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.	Up to 6 years
Secondary	Relapse Free Survival (RFS) for Participants with AML or MDS	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.	Up to 6 years
Secondary	Event Free Survival (EFS) for Participants with AML or MDS	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.	Up to 6 years
Secondary	Overall Survival (OS) for Participants with AML or MDS	The length of overall survival will be measured from the date of study treatment initiation until the date of death from any cause.	Up to 6 years
Secondary	Level of minimal residual disease (MRD) Negativity Using a Multiparameter Flow Cytometry-Based Assay for Participants on Treatment		Up to 6 years
Secondary	Complete Remission with Partial Hematologic Recovery (CRh)		Up to 6 years

External Links

•   Gilead Clinical Trials Website