This phase II clinical trial is studying how well selumetinib works in treating patients with recurrent or refractory acute myeloid leukemia. Selumetinib may stop the growth of cancer by blocking some of the enzymes needed for cell growth
PRIMARY OBJECTIVES: I. To determine the response rate (includes complete response-CR, complete response with incomplete count recovery CRi, partial response-PR, and minor response-MR) to AZD6244 (selumetinib). SECONDARY OBJECTIVES: I. To determine the effects of AZD6244 in AML samples on p-ERK and evaluate the potential utility of p-ERK inhibition as a surrogate marker of biologic activity. II. To correlate the effects of AZD6244 with the presence (or absence) of mutated RAS or FLT-3 at baseline. III. To assess the safety profile of AZD6244 in patients with AML. OUTLINE: Patients receive selumetinib orally (PO) twice daily (BID) on days 1 -28. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed for 52 weeks.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
47
Given PO
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, United States
Response Rate for Subjects Without FLT3 ITD Mutation
Responses were defined using standard criteria developed by an International Working Group. \[Cheson BD, Bennett JM, Kopecky KJ, Buchner T, Willman CL, Estey EH, et al. Revised recommendations of the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia. J Clin Oncol 2003;21:4642-9.\] In this primary outcome, we report the proportion of subjects without FLT3 ITD mutation that experienced a complete response (CR), partial response (PR), minor response (MR), or unconfirmed minor response (uMR).
Time frame: Up to 52 weeks
Proportion of Subjects With Baseline p-ERK Activation
Proportion of subjects with baseline p-ERK activation
Time frame: baseline (0 weeks)
Proportion of Subjects With NRAS Mutation
Proportion of Subjects With NRAS Mutation
Time frame: baseline (0 weeks)
Proportion of Subjects With KRAS Mutation
Proportion of subjects with KRAS mutation
Time frame: baseline (0 weeks)
Proportion of Subjects With FLT3 ITD Mutation
Proportion of subjects with FLT3 ITD mutation
Time frame: baseline (0 weeks)
Proportion of Subjects With KIT Mutation
Proportion of subjects with KIT mutation
Time frame: baseline (0 weeks)
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