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)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the optimal dose and side effects of a treatment combination for acute myeloid leukemia (AML), a type of blood cancer. The treatment combines three drugs: magrolimab, which may inhibit cancer cell growth; azacitidine, which kills or halts the spread of cancer cells; and venetoclax, which blocks a protein essential for cancer cell survival. It targets individuals with AML, particularly those who have not responded to other treatments or cannot tolerate intensive chemotherapy. Participants should have conditions such as difficult-to-treat AML or AML that has recurred after other treatments. The study seeks to improve AML control by using these three drugs together. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment combination.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop your current medications. However, you cannot take other chemotherapy or anti-leukemic agents during the study, except for certain allowed medications like hydroxyurea for specific conditions. It's best to discuss your current medications with the study team to ensure they don't interfere with the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of azacitidine, venetoclax, and magrolimab is generally safe for patients. Studies have found that most people tolerate this three-drug treatment well, although it might not significantly extend the lives of those with acute myeloid leukemia (AML). Some side effects have been noted, but they are usually mild and manageable. This suggests that the treatment is safe enough for those considering joining a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this triple-drug therapy for Acute Myeloid Leukemia (AML) because it combines azacitidine, venetoclax, and magrolimab in a unique way. Unlike standard treatments, which often focus on chemotherapy alone, this regimen includes magrolimab, an antibody that targets CD47 on cancer cells, helping the immune system recognize and destroy them. Additionally, venetoclax inhibits BCL-2, a protein that helps cancer cells survive, making them more susceptible to treatment. This combination not only aims to tackle the leukemia cells more effectively but also brings hope for improved outcomes by attacking the cancer from multiple angles.

What evidence suggests that this trial's treatments could be effective for acute myeloid leukemia?

This trial investigates the use of a combination of three drugs—azacitidine, venetoclax, and magrolimab—to treat acute myeloid leukemia (AML). Studies have shown that azacitidine and venetoclax can improve outcomes for older patients or those unfit for intensive treatment who have just been diagnosed with AML. The trial includes magrolimab, a monoclonal antibody, because it might help stop cancer cells from growing and spreading. However, adding magrolimab to azacitidine and venetoclax has not significantly improved survival rates in patients with untreated AML. While this combination shows promise, more research is needed to understand its effectiveness better. ^{4 6 7 8 9}

Who Is on the Research Team?

Naval Daver, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Citations

1. ashpublications.org ashpublications.org/blood/article/146/5/601/536723/The-ENHANCE-3-study-venetoclax-and-azacitidine

The ENHANCE-3 study: venetoclax and azacitidine plus ... Addition of magrolimab to venetoclax and azacitidine resulted in more fatal adverse events (19.0% vs 11.4%), primarily driven by grade 5 infections (11.1% vs ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12073901/

Phase 2 Multi‐Arm Study of Magrolimab Combinations ... This phase 2 study evaluated magrolimab+venetoclax (VEN)+azacitidine (AZA) in untreated, unfit acute myeloid leukaemia (AML) and ...

3. aacrjournals.org aacrjournals.org/clincancerres/article/31/12/2386/762776/Azacitidine-Venetoclax-and-Magrolimab-in-Newly

Azacitidine, Venetoclax, and Magrolimab in Newly Diagnosed ... Azacitidine and venetoclax improved the outcomes of older and unfit patients with newly diagnosed acute myeloid leukemia (AML); however, in patients with high- ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0006497125009115

venetoclax and azacitidine plus magrolimab or placebo for ... Addition of magrolimab to venetoclax and azacitidine did not improve OS in patients with untreated AML ineligible for IC.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04778397

NCT04778397 | Study of Magrolimab in Combination With ... The goal of this clinical study is to compare the effectiveness of the study drugs, magrolimab in combination with azacitidine, versus venetoclax in combination ...

6. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/735/531085/Phase-1b-2-Study-of-Magrolimab-Magro-Azacitidine

Phase 1b/2 Study of Magrolimab (Magro), Azacitidine (AZA ... Herein, we report final clinical data for the full cohort of pts enrolled in the study and additionally include previously undescribed genomic ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40198272/

Azacitidine, Venetoclax, and Magrolimab in Newly Diagnosed ... The triplet regimen was safe but did not lead to promising survival outcomes.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT05079230

NCT05079230 | Study of Magrolimab Versus Placebo in ... A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety and Efficacy of Magrolimab Versus Placebo in Combination With Venetoclax ...

9. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40233321/

venetoclax and azacitidine plus magrolimab or placebo for ... The ENHANCE-3 study: venetoclax and azacitidine plus magrolimab or placebo for untreated AML unfit for intensive therapy · Authors · Affiliations.