Spots Global Cancer Trial Database for Venetoclax in Combination With ASTX727 for the Treatment of Chronic Myelomonocytic Leukemia and Other Myelodysplastic Syndrome/Myeloproliferative Neoplasm

Study Description

Brief Summary: This phase II trial tests whether decitabine and cedazuridine (ASTX727) in combination with venetoclax work better than ASTX727 alone at decreasing symptoms of bone marrow cancer in patients with chronic myelomonocytic leukemia (CMML), myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN) with excess blasts. Blasts are immature blood cells. 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. Cobimetinib is used in patients whose cancer has a mutated (changed) form of a gene called BRAF. It is in a class of medications called kinase inhibitors. It works by blocking the action of an abnormal protein that signals cancer cells to multiply. This helps slow or stop the spread 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. The combination of ASTX727 and venetoclax may be more effective in reducing the cancer signs and symptoms in patients with CMML, or MDS/MPN with excess blasts.

Detailed Description: PRIMARY OBJECTIVE: I. To evaluate the complete remission rates of ASTX727 and ASTX727 plus venetoclax in subjects with chronic myelomonocytic leukemia (CMML) and non-CMML myelodysplastic syndrome (MDS)/myeloproliferative neoplasm (MPN) with excess (\>= 5%) blasts. SECONDARY OBJECTIVES: I. To evaluate the overall response rate (complete response \[CR\] + partial response \[PR\] + marrow response with erythroid response) of ASTX727 versus ASTX727 + venetoclax in this patient population. II. To determine the overall survival, progression-free survival, allogeneic hematopoietic stem cell transplantation rate, clearance of the malignant clone, clonality at time of hematologic remission, number of red cell and platelet transfusions required and toxicity of ASTX727 versus ASTX727 + venetoclax. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I (COMBINATION THERAPY): Patients receive ASTX727 orally (PO) daily (QD) for 5 consecutive days starting on day 3 of treatment cycle 1; followed by day 1 of each subsequent cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also receive venetoclax PO QD on days 1 through 14 of each treatment cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo bone marrow biopsies, and collection of blood and buccal samples throughout the study. ARM II (MONO THERAPY): Patients receive ASTX727 PO QD for 5 consecutive days starting on day 3 of treatment cycle 1; followed by day 1 of each subsequent cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who do not have response to treatment may cross over to Arm I. Patients also undergo bone marrow biopsies, and collection of blood and buccal samples throughout the study. After completion of study treatment, patients are followed for 2 years.

Keywords

Eligibility

Minimum Age: 18 Years

Eligible Ages: ADULT, OLDER_ADULT

Sex: ALL

Healthy Volunteers: No

Locations

Contact Details

Useful links and downloads for this trial