IDH Inhibitors + Azacitidine/Venetoclax for Acute Myeloid Leukemia
Trial Summary
What is the purpose of this trial?
This phase II study compares the order of treatment with ivosidenib or enasidenib and azacitidine plus venetoclax in treating older patients with acute myeloid leukemia with genetic changes in the IDH1 or IDH2 genes (IDH mutated). Ivosidenib is in a class of medications called isocitrate dehydrogenase-1 (IDH1) inhibitors. It works by slowing or stopping the growth of cancer cells. Enasidenib is in a class of medications called an IDH2 inhibitor. It also works by slowing or stopping the growth of cancer cells. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Azacitidine is in a class of medications called demethylation agents. It works by helping the bone marrow to produce normal blood cells and by killing abnormal cells. This study may help researchers determine which treatment order is best for older patients with IDH mutated acute myeloid leukemia: 1) ivosidenib or enasidenib followed by azacitidine plus venetoclax; or 2) azacitidine plus venetoclax followed by ivosidenib or enasidenib.
Will I have to stop taking my current medications?
The trial information does not specify if you need to stop taking your current medications. However, it mentions that hydroxyurea can be used to manage white blood cell levels, which suggests some medications might be allowed. It's best to discuss your specific medications with the trial team.
What data supports the effectiveness of the drug combination of IDH inhibitors, azacitidine, and venetoclax for treating acute myeloid leukemia?
Research shows that combining venetoclax with azacitidine significantly improves survival in patients with acute myeloid leukemia and IDH mutations. In a study, venetoclax plus azacitidine had a high probability of being the best treatment option, with a complete remission rate of over 70% in elderly patients.12345
Is the combination of IDH inhibitors, azacitidine, and venetoclax safe for treating acute myeloid leukemia?
The combination of IDH inhibitors, azacitidine, and venetoclax has been studied for safety in patients with acute myeloid leukemia. Most side effects were mild to moderate, and the treatment was generally well-tolerated, with no maximum tolerated dose reached in trials. This suggests that the treatment is generally safe for use in humans.12367
What makes the drug combination of IDH inhibitors, azacitidine, and venetoclax unique for treating acute myeloid leukemia?
This drug combination is unique because it targets specific genetic mutations (IDH1/2) in acute myeloid leukemia, potentially improving survival rates compared to other treatments. Venetoclax, when combined with azacitidine, has shown promising results in patients with these mutations, offering a new option for those who may not respond well to other therapies.12368
Research Team
Alice Mims
Principal Investigator
Ohio State University Comprehensive Cancer Center
Eligibility Criteria
This trial is for older patients with a new diagnosis of acute myeloid leukemia (AML) that has specific genetic changes known as IDH mutations. They should not be candidates for intensive induction therapy, have decent organ function and performance status, and must agree to use contraception if applicable.Inclusion Criteria
Exclusion Criteria
Timeline
Screening
Participants are screened for eligibility to participate in the trial
Treatment
Participants receive sequential treatment with either IDH inhibitor plus azacitidine or venetoclax plus azacitidine, depending on randomization
Follow-up
Participants are monitored for safety and effectiveness after treatment completion
Treatment Details
Interventions
- Azacitidine
- Enasidenib
- Ivosidenib
- Venetoclax
Azacitidine is already approved in European Union, United States, Canada, Japan for the following indications:
- Acute myeloid leukemia
- Chronic myelomonocytic leukemia
- Myelodysplastic syndromes
- Myelodysplastic syndromes
- Chronic myelomonocytic leukemia
- Myelodysplastic syndromes
- Acute myeloid leukemia
- Myelodysplastic syndromes
- Acute myeloid leukemia
Find a Clinic Near You
Who Is Running the Clinical Trial?
Alice Mims
Lead Sponsor
National Cancer Institute (NCI)
Collaborator