ASTX727, Venetoclax, and Gilteritinib for FLT3-Mutated AML or High-Risk MDS
This study is testing a combination of three medicines: ASTX727 (decitabine and cedazuridine), venetoclax, and gilteritinib. It's for adults aged 18 and older with acute myeloid leukemia (AML) that has a specific FLT3 gene change, or high-risk myelodysplastic syndrome (MDS). This includes people newly diagnosed, whose cancer has returned (relapsed), or whose cancer hasn't responded to other treatments (refractory). ASTX727 works by stopping cancer cells from growing. Venetoclax may stop cancer cells by blocking a protein called Bcl-2. Gilteritinib may stop cancer cells by blocking enzymes needed for their growth. The study aims to find the best dose of these medicines and see how well they work together. The study is currently recruiting 42 participants.
- Study design
- This is a Phase I/II study. The Phase I part will find the maximum tolerated dose, and the Phase II part will measure how many patients respond to the treatment.
- What's involved
- The primary endpoints are measured up to 28 days for Phase I and up to 2 cycles (56 days) for Phase II. The study does not specify the number of visits or procedures.
- Compensation
- Not stated in the trial record.
- Follow-up
- Overall response is measured up to 2 cycles of treatment (1 cycle = 28 days). The record does not specify follow-up beyond this.
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NCT05010122
ASTX727, Venetoclax, and Gilteritinib for the Treatment of Newly Diagnosed, Relapsed or Refractory FLT3-Mutated Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome
Recruiting
PHASE1Ages 18+InterventionalTreatmentM.D. Anderson Cancer CenterInvestigator-initiated
~42 participants
Updated 2026-07-16 on ClinicalTrials.gov
What's tested:Decitabine and CedazuridineGilteritinibVenetoclax
At a glance
Recruiting sites
1 of 1 listed site is recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Maximum tolerated dose (Phase I)
Measured over Up to 28 days
+1 more outcome measured
Conditions
Where it's being run
1 sites across 1 statesTexas1
Study leadership
- Farhad Ravandi-Kashani · PRINCIPAL_INVESTIGATOR · M.D. Anderson Cancer Center
Who to contact
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Do you actually qualify for this trial?
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Eligibility criteria
Inclusion
Diagnosis:
Phase I cohort: Adults \>= 18 years with relapsed/refractory FLT3-mutated AML or myelodysplastic syndrome (MDS) that is intermediate-2 or high-risk by the International Prognostic Scoring System
Phase II cohort A: Adults \>= 18 years with newly diagnosed FLT3-mutated AML. Patients should meet the following criteria:
Confirmed newly diagnosed AML with FLT3 mutation
Ineligible for induction therapy defined as
Either age \>= 75
Or 18-74 with at least one comorbidity (congestive heart failure \[CHF\] requiring therapy or ejection fraction \[EF\] =\< 50%, diffusion capacity of the lung for carbon monoxide \[DLCO\] =\< 65% or forced expiratory volume in 1 second \[FEV1\] =\< 65%, or Eastern Cooperative Oncology Group \[ECOG\] 2 or 3, or other significant co-morbidity precluding use of cytotoxic chemotherapy as approved by the principal investigator (PI)
Phase II cohort B: Adults \>= 18 years with relapsed/refractory FLT3-mutated AML or MDS that is intermediate-2 or high-risk by the International Prognostic Scoring System who have received 1 prior therapy
For all cohorts, patients with either FLT3-ITD or FLT3 D835 mutations will be eligible
Performance status =\< 3 (Eastern Cooperative Oncology Group \[ECOG\] scale)
Total serum bilirubin =\< 2.5 x upper limit of normal (ULN), unless due to Gilbert's syndrome, hemolysis or the underlying leukemia approved by the PI
Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) =\< 3 x ULN, unless due to the underlying leukemia approved by the PI
Creatinine clearance \>= 30 mL/min
Ability to swallow
Signed informed consent
Hydroxyurea or one dose of cytarabine up to 1000 mg is allowed to reduce the white blood cell (WBC) to less than 25 x 10\^9/L prior to initiation of study treatment
Exclusion
Prior therapies
Phase I cohort: No restriction based on prior therapies
Phase II cohort A: Patients with prior therapy for AML are not eligible. Prior therapy for antecedent hematologic disorder is allowed including prior hypomethylating agent (HMA) therapy for MDS. Prior hydroxyurea or cytarabine given for purposes of cytoreduction is also allowed. Prior all trans-retinoic acid given for presumed acute promyelocytic leukemia is also allowed
Phase II cohort B: Patients with \>= 3 prior lines of therapy are not eligible. Stem cell transplantation, treatment given only for cytoreductive purposes (e.g. hydroxyurea), and growth factors do not count as lines of therapy for this purpose. Prior therapy with venetoclax and gilteritinib is allowed
Patients suitable for and willing to receive intensive induction chemotherapy (for Phase II cohort A only)
Congenital long QT syndrome or corrected QT (QTc) \> 450 msec. Repeat electrocardiograms (EKGs) after correction of electrolytes or discontinuation of QT prolonging medications are allowed to meet entry criteria
Active serious infection not controlled by oral or intravenous antibiotics (e.g. persistent fever or lack of improvement despite antimicrobial treatment)
Active grade III-V cardiac failure as defined by the New York Heart Association Criteria
Active central nervous system leukemia
Known hepatitis B surface antigen seropositive or known or suspected active hepatitis C infection
Note: Patients who have isolated positive hepatitis B core antibody (i.e., in the setting of negative hepatitis B surface antigen and negative hepatitis B surface antibody) must have an undetectable hepatitis B viral load. Patients who have positive hepatitis C antibody may be included if they have an undetectable hepatitis C viral load
Patients with a prior or concurrent malignancy whose natural history or treatment is not anticipated to interfere with the safety or efficacy assessment of the investigational regimen may be included only after discussion with the PI
Consumed strong inducer of CYP3A or p-glycoprotein within 3 days of study enrollment. Agents include but are not limited to: carbamazepine, phenytoin, rifampin, and St. John's wart
Treatment with any investigational antileukemic agents or chemotherapy agents in the last 7 days before study entry, unless full recovery from side effects has occurred or patient has rapidly progressive disease judged to be life-threatening by the investigator. Prior recent treatment with corticosteroids, hydroxyurea and/or cytarabine (given for cytoreduction) permitted. Use of hydroxyurea or one dose cytarabine to reduce WBC below 25 prior to initiation of study treatment is recommended
Pregnant women will not be eligible; women of childbearing potential should have a negative pregnancy test prior to entering on the study and be willing to use effective methods of contraception throughout the study period and for at least 6 months after the last dose of study drugs. Women do not have childbearing potential if they have had a hysterectomy or are postmenopausal without menses for 12 months. In addition, men enrolled on this study should understand the risks to any sexual partner of childbearing potential and should practice an effective method of birth control throughout the study period and for at least 4 months after the last dose of study drugs. Lactating women (or those planning to breastfeed) should not breastfeed during treatment of gilteritinib and for at least 2 months after the last dose of gilteritinib
Medical, psychiatric, cognitive or other conditions that compromise the patient's ability to understand the patient information, to give informed consent, to comply with the study protocol or to complete the study
What this trial measures
- Maximum tolerated dose (Phase I)Up to 28 days
- Overall response (OR) rate (Phase II)Up to 2 cycles of treatment (1 cycle = 28 days)
Will estimate the OR for the combination treatment (defined as the proportion of patients achieving complete response (CR) or incomplete hematologic recovery (CRi) within 2 cycles of treatment), along with the 95% credible interval.