Venetoclax + Azacitidine for Myelodysplastic Syndrome and Chronic Myelomonocytic Leukemia

Overseen By Guillermo Garcia-Manero

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: BCL2 inhibitors, CYP3A inducers

Disqualifiers: HIV, Hepatitis B/C, Cardiovascular, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 4-8 weeks per cycle

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the optimal dose and assess the side effects of combining venetoclax (a cancer treatment) and azacitidine (a chemotherapy drug) for certain blood disorders. These disorders include high-risk myelodysplastic syndrome, where the bone marrow doesn't produce enough healthy blood cells, and chronic myelomonocytic leukemia, a cancer affecting blood cells. The trial focuses on patients whose conditions have returned or did not respond to previous treatments. Individuals who have previously received HMA drugs without improvement, or whose disease relapsed, may be suitable candidates. As a Phase 1, Phase 2 trial, it seeks to understand how the treatment works in people and measure its effectiveness in an initial, smaller group.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications, but you cannot have taken strong or moderate CYP3A inducers within 7 days before starting the study treatment. Also, you should avoid grapefruit, Seville oranges, and starfruit 3 days before starting the treatment.

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

Research has shown that the combination of venetoclax and azacitidine has been tested for safety in people with blood cancers. In earlier studies, most participants tolerated this treatment well. Common side effects included low blood cell counts, nausea, and fatigue. Serious side effects were less common but could include infections due to a weakened immune system. These findings suggest that while side effects can occur, the treatment is generally manageable for many patients. The current trial aims to determine the optimal dose to balance effectiveness and side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of venetoclax and azacitidine for treating Myelodysplastic Syndrome (MDS) and Chronic Myelomonocytic Leukemia (CMML) because it offers a novel approach compared to the current standard treatments like hypomethylating agents alone. Venetoclax works by targeting and inhibiting a protein called BCL-2, which helps cancer cells survive; this mechanism is different from traditional therapies. Additionally, combining venetoclax with azacitidine may enhance the treatment's effectiveness by attacking the cancer cells from different angles, potentially leading to better outcomes for patients.

What evidence suggests that venetoclax and azacitidine might be effective for myelodysplastic syndrome or chronic myelomonocytic leukemia?

Research has shown that combining venetoclax and azacitidine holds promise for treating high-risk myelodysplastic syndrome and chronic myelomonocytic leukemia. In this trial, participants will receive this combination treatment, which studies indicate can be effective, particularly when other treatments have failed. Venetoclax blocks proteins essential for cancer cell growth, while azacitidine prevents cancer cells from growing and spreading. Early results suggest this combination is both safe and effective against these blood cancers. This treatment has demonstrated encouraging results in patients with these conditions. ^{1 2 4 5 6}

Who Is on the Research Team?

Guillermo Garcia-Manero

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with high-risk myelodysplastic syndrome or chronic myelomonocytic leukemia that's resistant to treatment or has returned. They must have had previous unsuccessful therapy, be in good physical condition (ECOG/PS ≤2), and have proper liver and kidney function. Women of childbearing age need a negative pregnancy test and agree to contraception; men also must use birth control.

Inclusion Criteria

Signed written informed consent

I have CMML or therapy-related MDS that has not responded to treatment.

Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) =< 3.0 x ULN unless considered due to leukemic involvement

Exclusion Criteria

I have side effects from previous cancer treatments that have not fully healed.

I have a chronic illness or allergy that may affect my participation in the study.

I have hepatitis B or C but my viral load is undetectable.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive venetoclax orally daily on days 1-14 and azacitidine intravenously or subcutaneously on days 1-5. Cycles repeat every 4-8 weeks in the absence of disease progression or unacceptable toxicity.

4-8 weeks per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-ups within 30 days and then every 3-6 months for up to 5 years.

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Azacitidine
• Venetoclax

Trial Overview The trial is testing the combination of two drugs: Venetoclax, which may block cancer cell growth enzymes, and Azacitidine, a chemotherapy drug that kills or stops cancer cells from growing. The study aims to find the best dose and see how well these drugs work together against specific blood cancers.

How Is the Trial Designed?

Group I: Treatment (venetoclax, azacitidine) Experimental Treatment 2 Interventions

Patients receive venetoclax PO daily on days 1-14 and azacitidine IV over 15 minutes or SC on days 1-5. Cycles repeat every 4-8 weeks 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+

Genentech, Inc.

Industry Sponsor

Trials

1,578

Recruited

569,000+

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04160052

Venetoclax and Azacitidine for the Treatment of High-Risk ... This phase I/II trial studies the side effects and best dose of venetoclax when given together with azacitidine in treating patients with high-risk ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10100228/

A phase 1b study of venetoclax and azacitidine ... Due to the limited efficacy with venetoclax monotherapy, this report primarily focuses on the results of the combination of venetoclax and azacitidine in ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05768711

Study Details | NCT05768711 | Azacitidine Combined With ... ... efficacy and safety of Azacitidine combined with Venetoclax in patients with higher-risk chronic myelomonocytic leukemia. Detailed Description. AVENHIR trial ...

4. tandfonline.com tandfonline.com/doi/full/10.1080/16078454.2023.2198098

Full article: The efficacy and safety of venetoclax and ... The present meta-analysis demonstrated that the Ven + AZA regimen is efficacious for the treatment of AML and MDS, with it being more effective for ND-AML than ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36063832/

Azacitidine plus venetoclax in patients with high-risk ... Azacitidine with venetoclax is safe and shows encouraging activity in patients with high-risk myelodysplastic syndromes or chronic myelomonocytic leukaemia.

6. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT04160052/

Clinical Trial: NCT04160052 This phase I/II trial studies the side effects and best dose of venetoclax when given together with azacitidine in treating patients with high- ...