Venetoclax in Combination With ASTX727 for the Treatment of Chronic Myelomonocytic Leukemia and Other Myelodysplastic Syndrome/Myeloproliferative Neoplasm

Conditions

• Chronic Myelomonocytic Leukemia
• Myelodysplastic Syndrome
• Myelodysplastic Syndrome With Excess Blasts
• Myelodysplastic/Myeloproliferative Neoplasm
• Myeloproliferative Neoplasm

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Biospecimen Collection — PROCEDURE
  Undergo collection of blood and buccal samples
• Bone Marrow Aspiration — PROCEDURE
  Undergo bone marrow aspiration
• Bone Marrow Biopsy — PROCEDURE
  Undergo bone marrow biopsy
• Decitabine and Cedazuridine — DRUG
  Given PO
• Venetoclax — DRUG
  Given PO

Study Details

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. Cedazuridine is in a class of medications called cytidine deaminase inhibitors. It prevents the breakdown of decitabine, making it more available in the body so that decitabine will have a greater effect. 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.

Key Dates

Start date

Jun 27, 2023

Status verified

Jan 2026

Primary completion

Aug 31, 2026

Completion

Aug 31, 2026

Study Design

Enrollment

132 participants (estimated)

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

TREATMENT

Arms

• Experimental: Arm I (ASTX727, venetoclax)
  Patients receive ASTX727 PO QD on days 1-5 of each cycle and venetoclax PO QD on days 1-14 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo bone marrow biopsy and aspiration and collection of blood samples throughout the study and undergo buccal swab sample collection at screening.
• Active Comparator: Arm II (ASTX727)
  Patients receive ASTX727 PO QD on days 1-5 of each 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 biopsy and aspiration and collection of blood samples throughout the study and undergo buccal swab sample collection at screening.

Primary Outcome Measure

Complete response rate [ Time Frame: Up to 4 cycles ]

Locations (33)

Find similar trials in Phoenix, AZ

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