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RECRUITINGPHASE1/PHASE2

Azacitidine and Quizartinib for the Treatment of Myelodysplastic Syndrome or Myelodysplastic/Myeloproliferative Neoplasm With FLT3 or CBL Mutations

Phase I/II Study of Azacitidine in Combination With Quizartinib for Patients With Myelodysplastic Syndromes and Myelodysplastic/Myeloproliferative Neoplasms With FLT3 or CBL Mutations

NCT04493138•M.D. Anderson Cancer Center

View on ClinicalTrials.gov

Summary

This phase I/II trial studies the side effects and best dose of quizartinib when given with azacitidine and to see how well they work in treating patients with myelodysplastic syndrome or myelodysplastic/myeloproliferative neoplasm with FLT3 or CBL mutations. Chemotherapy drugs, such as azacitidine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Quizartinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving azacitidine and quizartinib may help to control myelodysplastic syndrome or myelodysplastic/myeloproliferative neoplasm.

Detailed Description

PRIMARY OBJECTIVES: I. To determine the safety, tolerability and maximum tolerable dose (MTD) of quizartinib in combination with azacytidine. II. To assess overall response (ORR) rate to quizartinib in combination with azacitidine. SECONDARY OBJECTIVES: I. To assess overall survival (OS), duration of response, leukemia-free survival (LFS), relapse-free survival (RFS) and safety profile. II. Correlative studies. OUTLINE: This is a phase I, dose-escalation study of quizartinib followed by a phase II study. Patients receive azacitidine subcutaneously (SC) or intravenously (IV) over about 30 minutes on days 1-5 and quizartinib orally (PO) once daily (QD) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•1. Age ≥ 18 years as MDS is a very rare disease in the pediatric setting.
•2. Diagnosis of MDS or MDS/MPN including CMML according to WHO.
•3. For hypomethylating agent naïve patients: int-2 or higher by IPSS or \>5% bone marrow blasts if MDS or dysplastic CMML (WBC \<13x109/L). Patients with proliferative (WBC \>/= 13x109/L) CMML or MDS/MPN, or those with dysplastic CMML with high-risk molecular features (mutations in ASXL1, TP53 or more than 3 mutations) are also eligible independently of IPSS risk score or bone marrow blast percentage.
•4. For patients with prior hypomethylating agent therapy: no response after 6 cycles of azacitidine, decitabine, guadecitabine or ASTX727 or relapse or progression after any number of cycles.
•5. Detectable FLT3-ITD mutation in bone marrow and/or peripheral blood, or presence of CBL exon 8 or 9 deletions or point mutations.
•6. Serum creatinine \</= 2xULN.
•7. Adequate hepatic function with total bilirubin \<2x ULN (will allow less than 5xULN if Gilbert's at investigator's discretion), AST or ALT \</=3xULN.
•8. ECOG Performance Status 0-2.
•9. Patient must have signed an informed consent document indicating that the patient understands the purpose of and procedures required for the study and is willing to participate in the study.
•10. Prior hydroxyurea for control of leukocytosis or use of hematopoietic growth factors (eg, G-CSF, GM-CSF, procrit, aranesp, thrombopoietins) is allowed at any time prior to or during study if considered to be in the best interest of the patient.
+13 more criteria

Exclusion Criteria

•1. Uncontrolled infection not adequately responding to appropriate antibiotics.
•2. Screening ECG with a QTcF \>450 msec. The QTcF interval will be calculated by Fridericia's correction factor (QTcF). The QTcF will be derived from the average QTcF in triplicate. Patients are excluded if they have QTcF \>450. Subjects with prolonged QTcF interval in the setting of RBBB (right bundle branch block) may participate upon review and approval by the principal investigator and following evaluation by cardiology consult.
•3. Patients with congenital long QT syndrome.
•4. History or presence of sustained ventricular tachycardia requiring medical intervention.
•5. Any history of clinically significant ventricular fibrillation or torsades de pointes.

Locations (1)

M D Anderson Cancer Center

Houston, Texas, United States

Key Dates

Start Date

July 21, 2020

Primary Completion Date

December 31, 2027

Completion Date

December 31, 2027

Last Updated

October 9, 2025

Enrollment

ESTIMATED participants

Conditions

Chronic Myelomonocytic LeukemiaMyelodysplastic SyndromeMyeloproliferative NeoplasmRecurrent Chronic Myelomonocytic LeukemiaRecurrent Myelodysplastic SyndromeRecurrent Myeloproliferative Neoplasm

Interventions

Azacitidine

DRUG

Quizartinib

DRUG

Contacts

Guillermo M. Bravo

CONTACT

713-794-3604 ggarciam@mdanderson.org

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: October 9, 2025Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

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Azacitidine and Quizartinib for the Treatment of Myelodysplastic Syndrome or Myelodysplastic/Myeloproliferative Neoplasm With FLT3 or CBL Mutations

Inclusion Criteria

Exclusion Criteria

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