Magrolimab, Azacitidine, and Venetoclax for the Treatment of Acute Myeloid Leukemia

NCT04435691 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: 2020-0027NCI-2020-04163
• Study Type: interventional
• Target: 110
• Locations: 1 country
• Sites: 1

Brief Summary

This phase Ib/II trial studies the side effects and best dose of magrolimab and venetoclax when given together with azacitidine and to see how well they work in treating patients with acute myeloid leukemia. Magrolimab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Chemotherapy drugs, such as azacitidine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Venetoclax may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Giving magrolimab, azacitidine, and venetoclax may help to control the disease.

Conditions

Acute Myeloid Leukemia; Recurrent Acute Myeloid Leukemia; Refractory Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (4)

• Maximum Tolerated Dose of the Combination Drugs (Phase Ib)

  The Maximum tolerated dose of Magrolimab, administered with Azacitidine 75 mg/m2 D1-7, and Venteoclax 400mg D1-28 will be selected at the end of the Phase 1b portion based on safety data.

  Up to 12 cycles

• Participants With a Response (Complete Remission + Complete Remission With Incomplete Count Recovery)

  Response is Complete Remission (CR) plus Complete remission with incomplete count recovery (CRi). Complete remission is peripheral blood counts, no circulating blasts, Neutrophil count \> 1.0 x 10\^9 L, Platelet count \> 100 x 10\^9/L and Bone marrow aspirate and biopsy \</=5% blasts no auer rods and no extramedullary leukemia. CRi is defined as peripheral blood counts, no circulating blasts, Neutrophil count \< 1.0 x 0\^9/L, OR platelet count\< 100 x 10\^9/L and Bone marrow aspirate and biopsy \</= 5% blasts, no auer rods and no extramedullary leukemia.

  Within 3 months of treatment initiation

• Event-free Survival

  Time from date of treatment start until the date of failure or death from any cause.

  Up to 4 years, 7 months and 15 days.

• Overall Survival

  Time from date of treatment start until date of death due to any cause or last Follow-up.

  Up to 4 years, 7 months and 15 days.

Study Arms (2)

Phase I MTD Treatment (azacitidine, venetoclax, magrolimab)

EXPERIMENTAL

Patients receive azacitidine SC or IV over 30-60 minutes on days 1-7, venetoclax PO QD on days 1-28 of cycle 1 (may be reduced to days 1-21 for subsequent cycles after principal investigator approval), and magrolimab IV over 2-3 hours on days 1, 4, 8, 11, 15, and 22 of cycle 1, days 1, 8, 15, and 22 of cycle 2, and days 1 and 15 of cycle 3 and subsequent cycles. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.

Drug: Azacitidine; Biological: Magrolimab; Drug: Venetoclax

Ph II (azacitidine, venetoclax, magrolimab)

EXPERIMENTAL

Participants in phase 2 were treated at the recommended phase 2 dose determined from the phase I portion of the study. Azacitidine SC or IV over 30-60 minutes on days 1-7, venetoclax PO QD on days 1-28 of cycle 1 (may be reduced to days 1-21 for subsequent cycles after principal investigator approval), and magrolimab IV over 2-3 hours on days 1, 4, 8, 11, 15, and 22 of cycle 1, days 1, 8, 15, and 22 of cycle 2, and days 1 and 15 of cycle 3 and subsequent cycles. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.

Drug: Azacitidine; Biological: Magrolimab; Drug: Venetoclax

Interventions

Azacitidine DRUG

Given SC or IV

Also known as: 5 AZC, 5-AC, 5-Azacytidine, 5-AZC, Azacytidine, Azacytidine, 5-, Ladakamycin, Mylosar, Onureg, U-18496, Vidaza

Ph II (azacitidine, venetoclax, magrolimab); Phase I MTD Treatment (azacitidine, venetoclax, magrolimab)

Magrolimab BIOLOGICAL

Given IV

Also known as: Hu5F9-G4

Ph II (azacitidine, venetoclax, magrolimab); Phase I MTD Treatment (azacitidine, venetoclax, magrolimab)

Venetoclax DRUG

Given PO

Also known as: ABT-0199, ABT-199, ABT199, GDC-0199, RG7601, Venclexta, Venclyxto

Ph II (azacitidine, venetoclax, magrolimab); Phase I MTD Treatment (azacitidine, venetoclax, magrolimab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of 1) WHO diagnosis of AML (excluding acute promyelocytic leukemia (APL)
• Phase Ib dose finding cohort: Participants aged ≥18 years old with relapsed/refractory AML are eligible if they are not eligible for potentially curative therapy such as effective salvage therapy or hematopoietic stem cell transplantation or who refuse these options at the time of enrollment. Participants must have received at least one prior therapy for AML. Participants may have received up to 2 prior therapies for AML (i.e. up to salvage 2 status allowed). Eastern Cooperative Oncology Group (ECOG) Performance Status ≤2
• Phase II (frontline cohort): Participants with newly diagnosed AML who are chemonaive (specified in 4.1.5) who are ineligible for intensive chemotherapy based on EITHER:
• A. ≥75 years of age OR
• B. \<75 years of age with at least 1 of the following relevant comorbidities:
• Poor performance status (ECOG) score of 2.
• Clinically significant heart or lung comorbidities, as reflected by at least 1 of:
• Left ventricular ejection fraction (LVEF) ≤50%.
• Lung diffusing capacity for carbon monoxide (DLCO) ≤65% of expected.
• Forced expiratory volume in 1 second (FEV1) ≤65% of expected.
• Chronic stable angina or congestive heart failure controlled with medication.
• Creatinine clearance ≥ 30 mL/min to \< 45 ml/min calculated by the Cockcroft-Gault formula or measured by 24 hours' urine collection
• Other contraindication(s) to anthracycline therapy (must be documented).
• Other comorbidity the investigator judges incompatible with intensive remission induction chemotherapy, which must be documented and approved by the PI."
• For participants with prior MDS or chronic myelomonocytic leukemia (CMML) or MPN who transformed to AML, therapy received for MDS, CMML, or MPN is NOT considered as prior therapy for AML. Participants with MDS or CMML treated with HMA therapies who progress to AML, and have no available therapies or are not candidates for available therapies, will be eligible to be enrolled to the relapsed/refractory cohort at the time of progression to AML. Temporary prior measures such as apheresis, ATRA, steroids while diagnostic work-up of AML is being performed are allowed and not counted as a prior salvage

You may not qualify if:

• Participants with known allergy or hypersensitivity to magrolimab, venetoclax, azacitidine or any of their components.
• Participants with any other known concurrent severe and/or uncontrolled medical condition including but not limited to diabetes, cardiovascular disease including hypertension, renal disease, or active uncontrolled infection, which could compromise participation in the study. Participants on active antineoplastic or radiation therapy for a concurrent malignancy at the time of screening. Maintenance therapy, hormonal therapy, or steroid therapy for well-controlled malignancy is allowed.
• Prior organ transplantation including allogenic stem-cell transplantation within 3 months prior to planned enrollment, active graft versus host disease (GVHD) \>Grade 1, or requiring transplant-related immunosuppression, excluding prednisone 10mg or equivalent steroid.
• Known inherited or acquired bleeding disorders
• Prior treatment with a CD47 or SIRP targeting agent.
• Participants with symptomatic CNS leukemia or patients with poorly controlled CNS leukemia.
• Participants with a known HIV infection that is not well controlled (i.e. any detectable circulating viral load) at the time of enrollment.
• Participants with known positive hepatitis B or C infection by serology, with the exception of those with an undetectable viral load within 3 months (Hepatitis B or C testing is not required prior to study entry). Subjects with serologic evidence of prior vaccination to HBV \[i.e., HBs Ag-, and anti-HBs+\] may participate.
• Patients who have consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or Starfruit within 3 days prior to the initiation of study treatment.
• Participants who have had any major surgical procedure within 14 days of Day 1.
• Other severe acute or chronic medical conditions that is active and not well controlled including colitis, inflammatory bowel disease, or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
• Active and uncontrolled disease (active infection requiring systemic therapy or fever likely secondary to infection within prior 48 hours): prophylactic antibiotics or prolonged course of IV antibiotics for controlled infection are allowed, uncontrolled hypertension despite adequate medical therapy, active and uncontrolled congestive heart failure NYHA class III/IV, clinically significant and uncontrolled arrhythmia) as judged by the treating physician.
• Participants unwilling or unable to comply with the protocol.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• MD Anderson Cancer Center

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Azacitidine; magrolimab; venetoclax

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Results Point of Contact

• Title: Naval Daver MD./Professor
• Organization: The University of Texas MD Anderson Cancer Center

ndaver@mdanderson.org

713-794-4392

Study Officials

• Naval G Daver

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 15, 2020
• First Posted: June 17, 2020
• Study Start: July 28, 2020
• Primary Completion: March 25, 2025
• Study Completion: March 25, 2025
• Last Updated: April 23, 2026
• Results First Posted: April 23, 2026

Record last verified: 2026-04

Locations

US (1)