Testing Oral Decitabine and Cedazuridine (ASTX727) in Combination With Venetoclax for Higher-Risk Acute Myeloid Leukemia Patients

Part of paid clinical trials in Birmingham, Alabama.

Sponsor
National Cancer Institute (NCI)
Study ID
NCT04817241
Phase
PHASE1/PHASE2
Status
Active Not Recruiting

Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - 65 Years
Healthy Volunteers
Not accepted

Interventions

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

Study Details

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.

Key Dates

Start date
Feb 10, 2022
Status verified
Nov 2025
Primary completion
Jun 6, 2025
Completion
Nov 5, 2026

Study Design

Enrollment
5 participants (actual)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Arm I (decitabine and cedazuridine, venetoclax)
    Patients receive ASTX727 PO QD at the recommended phase II dose and venetoclax PO QD on days 1-28 of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo bone marrow aspiration and biopsy and collection of blood samples throughout the trial.
  • Active Comparator: Arm II (cytarabine, daunorubicin)
    Patients receive cytarabine IV over 24 hours on days 1-7 of each cycle and daunorubicin IV over 10-30 minutes on days 1-3 of each cycle. Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo bone marrow aspiration and biopsy throughout the trial.
  • Experimental: Phase Ib (decitabine and cedazuridine, venetoclax)
    Patients receive ASTX727 PO QD on days 1-4 or 1-5 of each cycle and venetoclax PO QD on days 1-28 or days 1-21 of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo bone marrow aspiration and biopsy and collection of blood samples throughout the trial.

Primary Outcome Measure

Recommended safe phase 2 dose (RP2D) of decitabine and cedazuridine (ASTX727) in combination with venetoclax (Phase Ib) [ Time Frame: End of each cycle (1 cycle = 28 days) ]

Locations (7)

FacilityCityStateZIPSite coordinators
University of Alabama at Birmingham Cancer CenterBirminghamAlabama35233-
Yale UniversityNew HavenConnecticut06520-
Roswell Park Cancer InstituteBuffaloNew York14263-
Montefiore Medical Center - Moses CampusThe BronxNew York10467-
Montefiore Medical Center-Einstein CampusThe BronxNew York10461-
Vanderbilt University/Ingram Cancer CenterNashvilleTennessee37232-
University of Virginia Cancer CenterCharlottesvilleVirginia22908-

Find similar trials in Birmingham, AL

By condition
Leukemia (other)
By specialty
OncologyBlood cancer
By research site
University of Alabama at Birmingham Cancer Center· Birmingham, ALYale University· New Haven, CTRoswell Park Cancer Institute· Buffalo, NYMontefiore Medical Center - Moses Campus· The Bronx, NYMontefiore Medical Center-Einstein Campus· The Bronx, NYVanderbilt University/Ingram Cancer Center· Nashville, TN

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