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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03248479
Recruitment Status : Recruiting
First Posted : August 14, 2017
Last Update Posted : June 4, 2020
Sponsor:
Collaborator:
California Institute for Regenerative Medicine (CIRM)
Information provided by (Responsible Party):
Forty Seven, Inc.

Brief 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.


Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia Myelodysplastic Syndromes Drug: Magrolimab Drug: Azacitidine Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 257 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 : September 12, 2017
Estimated Primary Completion Date : September 2020
Estimated Study Completion Date : August 2022


Arm Intervention/treatment
Experimental: Relapsed/Refractory AML or MDS
Patients with relapsed or refractory AML or intermediate/high risk MDS will receive magrolimab monotherapy or magrolimab in combination with azacitidine
Drug: Magrolimab
Magrolimab will be administered up to twice weekly.

Drug: Azacitidine
Azacitidine will be administered daily for 7 days in each 28-day cycle.
Other Name: VIDAZA

Experimental: Treatment-naive Unfit AML or MDS
Patients with previously untreated AML who are ineligible for standard induction chemotherapy, or previously untreated intermediate/high risk MDS, will receive magrolimab in combination with azacitidine
Drug: Magrolimab
Magrolimab will be administered up to twice weekly.

Drug: Azacitidine
Azacitidine will be administered daily for 7 days in each 28-day cycle.
Other Name: VIDAZA

Experimental: Rollover
Patients on a previous AML Phase 1 trial (SCI-CD47-002) with clinical benefit on magrolimab treatment will receive magrolimab monotherapy
Drug: Magrolimab
Magrolimab will be administered up to twice weekly.

Experimental: RBC transfusion-dependent low-risk MDS
Red Blood Cell (RBC) transfusion-dependent low-risk MDS patients will receive magrolimab monotherapy or magrolimab in combination with azacitidine
Drug: Magrolimab
Magrolimab will be administered up to twice weekly.

Drug: Azacitidine
Azacitidine will be administered daily for 5 days in each 28-day cycle.
Other Name: VIDAZA




Primary Outcome Measures :
  1. Adverse Events [ Time Frame: 28 days ]
    Adverse events according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 or customized AE severity grading as defined in the protocol

  2. Objective Response Rate [ Time Frame: 8 weeks ]
    Objective Response Rate as defined by the Investigator according to protocol-specified criteria based on European LeukemiaNet (ELN) AML recommendations (Döhner 2017), International Working Group (IWG) AML response criteria (Cheson 2003), or IWG MDS response criteria (Cheson 2006) where appropriate

  3. 8 week RBC transfusion independence rate [ Time Frame: 8 weeks ]
    • 8 week RBC transfusion independence rate for patients with low risk MDS as defined by the lack of RBC transfusions for at least an 8 week consecutive period at any time after starting therapy



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03248479


Contacts
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Contact: Mark Chao, MD PhD 1-650-352-4150 medical@fortyseveninc.com
Contact: Jin Xu, PhD 1-650-352-4150 medical@fortyseveninc.com

Locations
Show Show 28 study locations
Sponsors and Collaborators
Forty Seven, Inc.
California Institute for Regenerative Medicine (CIRM)
Investigators
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Study Chair: Mark Chao, MD PhD Forty Seven, Inc.
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Responsible Party: Forty Seven, Inc.
ClinicalTrials.gov Identifier: NCT03248479    
Other Study ID Numbers: 5F9005
First Posted: August 14, 2017    Key Record Dates
Last Update Posted: June 4, 2020
Last Verified: June 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Forty Seven, Inc.:
magrolimab
CD47
azacitidine
Hu5F9-G4
Additional relevant MeSH terms:
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Hematologic Neoplasms
Myelodysplastic Syndromes
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Neoplasms by Site
Azacitidine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Enzyme Inhibitors