Triple-Drug Therapy for Acute Myeloid Leukemia

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: CD47 agents

Disqualifiers: Diabetes, Cardiovascular disease, Renal disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

Duration: Up to 12 cycles (28 days each)

110 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Research Team

Naval Daver, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

Adults with acute myeloid leukemia (AML) who are either newly diagnosed with poor risk factors or have relapsed/refractory AML after previous treatments. Participants must be fit enough for the trial, not eligible for intensive chemotherapy due to age/comorbidities, and should not have uncontrolled diseases or known allergies to the drugs being tested.

Inclusion Criteria

I have been diagnosed with AML, not including APL.

I agree to use birth control during the study and for 4 months (women) or 3 months (men) after.

I am 18 or older with AML that has come back or didn't respond to treatment, and I can't or won't undergo potentially curative therapy. I've had up to 2 treatments for AML.

Exclusion Criteria

I am willing and able to follow the study's requirements.

I do not have an active infection or fever from an infection in the last 2 days.

Patients with known positive hepatitis B or C infection by serology, with the exception of those with an undetectable viral load within 3 months

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive azacitidine, venetoclax, and magrolimab in cycles. Azacitidine is administered SC or IV on days 1-7, venetoclax orally on days 1-28 of cycle 1 (may be reduced to days 1-21 for subsequent cycles), and magrolimab IV on specified days of each cycle. Treatment repeats every 28 days for up to 12 cycles.

Up to 12 cycles (28 days each)

Multiple visits per cycle for drug administration

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up visits at 30 and 100 days.

100 days

2 visits (in-person) at 30 and 100 days

Treatment Details

Interventions

• Azacitidine
• Magrolimab
• Venetoclax

Trial Overview The trial is testing a combination of magrolimab, azacitidine, and venetoclax in patients with AML. Magrolimab is an antibody that may stop cancer growth; azacitidine interferes with cell division; venetoclax blocks proteins needed by cancer cells.

Participant Groups

Group I: Treatment (azacitidine, venetoclax, magrolimab) Experimental Treatment 3 Interventions

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.

Azacitidine is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Vidaza for:

• Acute myeloid leukemia
• Chronic myelomonocytic leukemia
• Myelodysplastic syndromes

Approved in United States as Vidaza for:

• Myelodysplastic syndromes
• Chronic myelomonocytic leukemia

Approved in Canada as Vidaza for:

• Myelodysplastic syndromes
• Acute myeloid leukemia

Approved in Japan as Vidaza for:

• Myelodysplastic syndromes
• Acute myeloid leukemia

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+