Actively Recruiting
A Phase I/II Study of ASTX727, Venetoclax, and Gilteritinib for Patients With Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome With an Activating FLT3 Mutation
Led by M.D. Anderson Cancer Center · Updated on 2026-02-18
42
Participants Needed
1
Research Sites
N/A
Total Duration
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AI-Summary
What this Trial Is About
Researchers are studying a combination of three chemotherapy drugs—ASTX727 (decitabine and cedazuridine), venetoclax, and gilteritinib—for patients with FLT3-mutated acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS). This phase I/II trial aims to find the best dose of these drugs together and evaluate their effect in treating newly diagnosed, relapsed, or refractory cases of these blood cancers. The study also explores how genetic factors and protein levels may affect treatment response and resistance. During the initial induction cycle, patients take decitabine and cedazuridine orally once daily for five days, along with venetoclax and gilteritinib daily for 28 days, unless the disease progresses or side effects occur. In consolidation cycles 2 to 24, patients continue taking decitabine and cedazuridine for five days, gilteritinib for 28 days, and venetoclax for 21 days every 28-day cycle. After 24 cycles, patients receive gilteritinib alone daily on a 28-day cycle. Treatment continues as long as there is no disease progression or unacceptable toxicity. Participants will be closely monitored through regular visits during treatment and after completion, with follow-ups at 30 days and every six months thereafter. Researchers will assess treatment responses including complete remission rates and minimal residual disease, as well as survival outcomes and safety. They will also track how many patients proceed to stem cell transplantation. Safety will be evaluated up to 30 days after treatment ends, and efficacy will be followed for up to two years.
CONDITIONS
Brief Title
ASTX727, Venetoclax, and Gilteritinib for the Treatment of Newly Diagnosed, Relapsed or Refractory FLT3-Mutated Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Adults 18 years or older with relapsed/refractory FLT3-mutated AML or intermediate-2/high-risk MDS
- Adults 18 years or older with newly diagnosed FLT3-mutated AML who are ineligible for induction therapy due to age or comorbidities
- Adults 18 years or older with relapsed/refractory FLT3-mutated AML or MDS with intermediate-2/high-risk who have received 1 prior therapy
- Patients with FLT3-ITD or FLT3 D835 mutations
- Performance status of 3 or less on ECOG scale
- Total serum bilirubin less than or equal to 2.5 times upper limit of normal unless due to specific conditions
- ALT or AST less than or equal to 3 times upper limit of normal unless due to leukemia
- Creatinine clearance of 30 mL/min or higher
- Ability to swallow medications
- Signed informed consent
- Use of hydroxyurea or one dose cytarabine to reduce white blood cell count prior to study allowed
You will not qualify if you...
- Patients in Phase II cohort A with prior therapy for AML (except prior therapy for antecedent hematologic disorder allowed)
- Patients in Phase II cohort B with 3 or more prior lines of therapy
- Patients suitable for and willing to receive intensive induction chemotherapy (Phase II cohort A only)
- Congenital long QT syndrome or corrected QT interval greater than 450 msec
- Active serious infection not controlled by antibiotics
- Active grade III-V cardiac failure
- Active central nervous system leukemia
- Known hepatitis B surface antigen positive or active hepatitis C infection unless viral load is undetectable
- Prior or concurrent malignancy that may interfere with safety or efficacy assessments unless approved
- Use of strong CYP3A or p-glycoprotein inducers within 3 days before enrollment
- Treatment with investigational antileukemic or chemotherapy agents within 7 days before study entry unless recovered from side effects
- Pregnant or breastfeeding women, or those unwilling to use effective contraception
- Medical, psychiatric, cognitive, or other conditions preventing informed consent or study compliance
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - Up to 24 cycles of 28 days each for induction and consolidation, followed by maintenance cycles repeating every 28 days in the absence of disease progression or unacceptable toxicity.
Participants receive oral treatment cycles including induction with decitabine and cedazuridine, venetoclax, and gilteritinib, followed by consolidation and maintenance phases with adjustments to medication schedules based on response and tolerance.
Monthly visits for treatment cycles up to 24 months
Duration - Initial follow-up at 30 days post-treatment, then every 6 months thereafter
After completing study treatment, participants are followed up to monitor health status and any long-term effects of treatment.
1 visit at 30 days post-treatment and follow-up visits every 6 months
Trial Site Locations
Total: 1 location
1
M D Anderson Cancer Center
Houston, Texas, United States, 77030
Actively Recruiting
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
1
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