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.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
58
Given SC or IV
Given PO
M D Anderson Cancer Center
Houston, Texas, United States
RECRUITINGOverall response rate
Will be defined as complete remission, partial remission, complete remission with incomplete count recovery, marrow compete remission or hematological improvement. Will be estimated for all patients along with the 95% credible interval.
Time frame: At least 4 cycles of therapy in the absence of progression (1 cycle = 28 days)
Overall survival
Will be listed and summarized by the Kaplan-Meier estimator.
Time frame: Time from treatment start till death or last follow-up, assessed up to 2 years
Duration of response
Will be listed and summarized by the Kaplan-Meier estimator.
Time frame: Duration from the first documented onset of partial response or complete response to the date of progressive disease/relapse, assessed up to 2 years
Relapse-free survival
Will be listed and summarized by the Kaplan-Meier estimator.
Time frame: Time from start of response to the date of event defined as the first documented progressive disease/relapse or death, whichever comes first, assessed up to 2 years
Leukemia free survival
Will be listed and summarized by the Kaplan-Meier estimator.
Time frame: Time from treatment start to the time of progression to leukemia or death, assessed up to 2 years
Incidence of adverse events (AEs)
The severity of the toxicities will be graded according to the latest version of National Cancer Institute Common Terminology Criteria for Adverse Events. The number and percent of subjects with treatment-emergent adverse events will be summarized according to intensity and drug relationship, and categorized by System Organ Class and preferred term by dose level/Part. All reported AEs that occur after signing informed consent will be included in the analysis of all reported AEs. Exposure to study drug and reasons for discontinuation of study drug will be tabulated.
Time frame: Up to 2 years
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