Phase I/II Study of Azacitidine, Venetoclax, and Gilteritinib for FLT3-Mutated Leukemias and Myelodysplastic Syndromes
This study is testing a combination of three drugs: azacitidine, venetoclax, and gilteritinib. It's for adults (18 years or older) with certain types of blood cancers that have a specific genetic change called a FLT3 mutation. These cancers include acute myeloid leukemia (AML), chronic myelomonocytic leukemia (CMML), or high-risk myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN) that has either come back after treatment (recurrent) or hasn't responded to previous treatments (refractory). Venetoclax works by blocking a protein called Bcl-2, which cancer cells need to survive. The main goals are to find the safest dose of gilteritinib when given with the other drugs and to see how many patients respond to this treatment. The current status of this study is unclear.
- Study design
- This is a Phase I/II study, meaning it first looks for the best dose and then checks how well the treatment works. It plans to enroll 97 participants.
- What's involved
- Not specified in the trial record.
- Compensation
- Not stated in the trial record.
- Follow-up
- The study measures response rates up to 56 days (2 cycles) for the Phase II part, and the maximum-tolerated dose up to 28 days for Phase I.
AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.
NCT04140487
Azacitidine, Venetoclax, and Gilteritinib in Treating Patients With Recurrent/Refractory FLT3-Mutated Acute Myeloid Leukemia, Chronic Myelomonocytic Leukemia, or High-Risk Myelodysplastic Syndrome/Myeloproliferative Neoplasm
Recruiting
PHASE1Ages 18+InterventionalTreatmentM.D. Anderson Cancer CenterInvestigator-initiated
~97 participants
Updated 2026-04-16 on ClinicalTrials.gov
What's tested:AzacitidineGilteritinibVenetoclax
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 (MTD) of gilteritinib (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
- Nicholas Short · 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 CMML or other MDS/MPN 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
Phase II cohort B: Adults ≥ 18 years with relapsed/refractory FLT3-mutated AML or CMML or other MDS/MPN that is intermediate-2 or high-risk by the International Prognostic Scoring System
For all cohorts, patients with either FLT3-internal tandem duplication (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 principal investigator (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
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. 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: No restriction on number of prior therapies
Patients suitable for and willing to receive intensive induction chemotherapy (for Phase II cohort A only)
Congenital long QT syndrome or corrected QT interval by Fridericia (QTcF) \> 450 msec. Repeat electrocardiograms (EKGs) after correction of electrolytes or discontinuation of QT prolonging medications are allowed to meet entry criteria. In cases where QTcF \> 450 msec is considered to be falsely increased due to inaccurate automated reading and not clinically significant (e.g. due to bundle branch block), patients are still eligible if cardiologist reviews and documents that QTcF is ≤ 450 msec when manually measured
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 human immunodeficiency virus (HIV) seropositive
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 cytochrome P450, family 3, subfamily A (CYP3A) or p-glycoprotein within 3 days of study enrollment. Agents include but are not limited to: carbamazepine, phenytoin, rifampin, and St. John's wort
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
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 practice 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
What this trial measures
- Maximum-tolerated dose (MTD) of gilteritinib (Phase I)Up to 28 days
The MTD is the highest dose level in which \< 2 patients of 6 develop first cycle dose-limiting toxicity.
- Overall response rate (OR) (Phase II)Up to 56 days (2 cycles)
Will be defined as the complete remission/complete remission with incomplete count recovery (CR/CRi) rate. Will estimate the OR for the combination treatment along with the 95% credible interval.