Decitabine + Cedazuridine + Venetoclax for Acute Myeloid Leukemia
Trial Summary
Will I have to stop taking my current medications?
The trial protocol does not specify if you must stop taking your current medications. However, you cannot take certain medications that interact with the trial drugs, and you should discuss any current medications with the trial team to ensure they are permitted.
What data supports the effectiveness of the drug combination of Decitabine, Cedazuridine, and Venetoclax for treating Acute Myeloid Leukemia?
Research shows that combining Venetoclax with Decitabine improves survival and response rates in older adults with acute myeloid leukemia compared to Decitabine alone. In one study, patients receiving this combination had a longer median overall survival and higher response rates, indicating its effectiveness in treating this condition.12345
Is the combination of Decitabine, Cedazuridine, and Venetoclax safe for humans?
The combination of Venetoclax with Decitabine has been studied in older patients with acute myeloid leukemia and was generally well tolerated, with common side effects including nausea, diarrhea, and fatigue. No severe complications like tumor lysis syndrome (a condition where cancer cells break down rapidly) were observed in the studies.14567
How is the drug combination of Decitabine, Cedazuridine, and Venetoclax unique for treating acute myeloid leukemia?
This drug combination is unique because it combines Decitabine and Cedazuridine with Venetoclax, which has shown improved activity in high-risk acute myeloid leukemia patients, especially those who are older or unfit for intensive chemotherapy. The combination has demonstrated longer survival and higher response rates compared to Decitabine alone.24678
What is the purpose of this trial?
This phase Ib/II trial studies the effects of ASTX727 (decitabine and cedazuridine) in combination with venetoclax in treating patients with higher-risk acute myeloid leukemia patients who do not have a change in the gene called fms-like tyrosine kinase 3 (FLT3). Decitabine is in a class of medications called hypomethylation agents. It works by helping the bone marrow produce normal blood cells and by killing abnormal cells in the bone marrow. Cedazuridine is an enzyme inhibitor. It helps to increase the amount of decitabine in the body so that the medication will have a greater effect. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. Venetoclax may stop the growth of cancer cells by blocking BCL-2, a protein needed for cancer cell survival. Venetoclax and decitabine are commonly given together for older patients with AML ASTX727 (a pill form of decitabine + cedazuridine) has been found to be equal to decitabine (given intravenously), and this part of the study is to confirm that venetoclax and ASTX727 is as safe as venetoclax and decitabine given intravenously. This study allows for lowering doses of study drugs to assure the dose chosen for the randomized study (second portion of this trial) is safe and tolerable for people. Giving ASTX727 in combination with venetoclax may help in the treatment of patients with higher-risk acute myeloid leukemia.
Research Team
Michael Savona, MD
Principal Investigator
Yale University Cancer Center LAO
Eligibility Criteria
This trial is for adults aged 18-65 with higher-risk acute myeloid leukemia (AML) who haven't had certain previous treatments. Participants must have an ECOG performance status of <=2, no FLT3 gene mutations, and adequate organ function. They should not be pregnant or breastfeeding and must agree to use contraception.Inclusion Criteria
Exclusion Criteria
Timeline
Screening
Participants are screened for eligibility to participate in the trial
Phase Ib Treatment
Patients receive ASTX727 orally and venetoclax daily, with treatment repeating every 28 days for up to 12 cycles.
Phase II Treatment
Patients are randomized to receive either ASTX727 and venetoclax or cytarabine and daunorubicin, with treatment repeating every 28 days.
Follow-up
Participants are monitored for safety and effectiveness after treatment completion.
Treatment Details
Interventions
- Decitabine and Cedazuridine
- Venetoclax
Decitabine and Cedazuridine is already approved in European Union, United States for the following indications:
- Acute myeloid leukemia (AML) in adults who are ineligible for standard induction chemotherapy
- Adult patients with newly diagnosed acute myeloid leukemia (AML) who are 75 years or older, or who have comorbidities precluding intensive induction chemotherapy
Find a Clinic Near You
Who Is Running the Clinical Trial?
National Cancer Institute (NCI)
Lead Sponsor