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

ID#: NCT03248479

Age: 18 years - 66+

Gender: All

Healthy Subjects: No

Study Phase: Phase 1

Recruitment Status: Recruiting

Start Date: September 12, 2017

End Date: August 01, 2022

Contact Information:
Mark Chao, MD PhD
Jin Xu, PhD
Summary: This trial will evaluate magrolimab, a monoclonal antibody which is designed to block a protein called CD47, which is widely expressed on human cancer cells. Blocking CD47 with magrolimab may enable the body's immune system to find and destroy the cancer cells. In this study, magrolimab may be given alone or in combination with azacitidine to patients with acute myeloid leukemia (AML) or higher risk myelodysplastic syndrome (MDS). Azacitidine is a drug used for treatment of AML or MDS in patients who are not eligible for typical chemotherapy. The major aims of the study are: to confirm the safety and tolerability of magrolimab monotherapy in a relapsed/refractory AML and MDS population, and of magrolimab in combination with azacitidine in previously untreated AML and MDS; to evaluate the efficacy of magrolimab monotherapy in relapsed/refractory AML/MDS, and of magrolimab in combination with azacitidine in previously untreated AML/MDS, as measured by the objective response rate; and to evaluate the safety, tolerability, and efficacy of magrolimab monotherapy or combination with azacitidine in low-risk MDS patients as measured by RBC transfusion independence rate.

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-naïve/ Unfit Cohorts: Previously untreated patients with histological confirmation of AML who are ineligible for treatment with a standard cytarabine and anthracycline induction regimen; or previously untreated patients 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: Patients on active magrolimab therapy on the Phase 1 AML (SCI-CD47-002) trial who are deriving clinical benefit by Investigator assessment

4. RBC transfusion dependent low risk MDS cohort: Transfusion-dependent MDS patients 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 10E3/µL

- 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 patients in the Rollover cohort).

- Treatment-naïve/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