Study on ASTX727, Venetoclax, and Gilteritinib for Treating FLT3-Mutated Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome

Sponsor: M.D. Anderson Cancer Center

Sponsor score: 0
Inactive

ClinicalTrials ID:NCT05010122

Provider View

This clinical trial is testing a combination of three drugs—ASTX727, Venetoclax, and Gilteritinib—to find the best dose and see how well they work together in treating patients with FLT3-mutated acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS).

Patient Parameters

Program Overview

This study aims to determine the best dose and effectiveness of a combination of three drugs—ASTX727, Venetoclax, and Gilteritinib—in treating patients with FLT3-mutated acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS). These conditions may be newly diagnosed, have returned after treatment, or not responded to previous treatments. The drugs work by stopping cancer cells from growing and spreading. ASTX727 is a chemotherapy drug, Venetoclax blocks a protein needed for cancer cell survival, and Gilteritinib blocks enzymes needed for cell growth. The study hopes to find out if this combination can help control the disease.

Description

The study is divided into two phases. In Phase I, researchers will find the maximum safe dose of the drug combination for patients with relapsed or refractory FLT3-mutated AML or high-risk MDS. In Phase II, they will assess how well the treatment works in patients with newly diagnosed or relapsed/refractory FLT3-mutated AML or high-risk MDS.

The treatment plan includes three stages:

  1. Induction (Cycle 1): Patients take ASTX727, Venetoclax, and Gilteritinib daily for 28 days, unless the disease progresses or side effects become unacceptable.

  2. Consolidation (Cycles 2-24): Patients continue taking ASTX727 and Gilteritinib daily for 28 days, and Venetoclax for 21 days, repeating every 28 days for up to 23 cycles.

  3. Maintenance (Cycles 24+): Patients take Gilteritinib daily for 28 days, repeating every 28 days, as long as the disease does not progress or side effects remain manageable.

After completing the treatment, patients will have follow-up visits 30 days later and then every six months.

Eligibility Criteria

Inclusion Criteria

  • Adults aged 18 or older with FLT3-mutated AML or high-risk MDS.
  • For Phase I: Patients with relapsed or refractory AML or MDS.
  • For Phase II: Patients with newly diagnosed AML who cannot undergo standard induction therapy due to age (75 or older) or other health conditions.
  • Patients with either FLT3-ITD or FLT3 D835 mutations.
  • Performance status of 3 or less on the ECOG scale.
  • Adequate liver and kidney function as indicated by specific blood tests.
  • Ability to swallow pills.
  • Signed informed consent.
  • Allowed to take hydroxyurea or a single dose of cytarabine to lower white blood cell count before starting the study treatment.

Exclusion Criteria

  • For Phase II: Patients with prior AML treatment are not eligible, except for certain conditions.
  • Patients with three or more prior lines of therapy for Phase II cohort B.
  • Prior treatment with Gilteritinib.
  • Patients eligible and willing to receive intensive induction chemotherapy (Phase II cohort A).
  • Certain heart conditions or serious infections.
  • Active central nervous system leukemia.
  • Known HIV or active hepatitis B or C infections.
  • Recent use of certain medications that affect drug metabolism.
  • Recent treatment with investigational or chemotherapy agents, unless fully recovered from side effects.
  • Pregnant or breastfeeding women, or those not willing to use contraception during and after the study.
  • Men must also use effective birth control during and after the study.

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