Imatinib Mesylate in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia Who Have Received Chemotherapy
RATIONALE: Imatinib mesylate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
PURPOSE: This phase II trial is studying how well imatinib mesylate works in treating patients with newly diagnosed acute myeloid leukemia who have received chemotherapy.
Drug: imatinib mesylate
Genetic: gene expression analysis
Genetic: mutation analysis
Genetic: polymerase chain reaction
Other: flow cytometry
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase 2 Study of Imatinib Mesylate (Gleevec) as Maintenance Therapy After Induction and Consolidation Chemotherapy in Patients With Newly Diagnosed C-kit Positive Acute Myeloid Leukemia|
- Progression-free survival for patients less than 60 years of age [ Time Frame: 13 months after treatment ] [ Designated as safety issue: No ]Progression free survival will be measured from the date of Complete Response (CR) to the date of relapse or death.
- Progression-free survival for patients 60 years of age and older [ Time Frame: 8 months after treatment ] [ Designated as safety issue: No ]Progression free survival will be measured from the date of Complete Response (CR) to the date of relapse or death.
- Toxicity as measured by NCI CTC v. 3.0 [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]The percentage and frequencies of patients going off study for various reasons will be summarized.
- Correlation of c-kit expression with multidrug resistance gene expression (MDR1, MRP1, LRP, and BCRP) and AF1q expression [ Time Frame: 24 months ] [ Designated as safety issue: No ]
|Study Start Date:||December 2008|
|Estimated Primary Completion Date:||November 2013 (Final data collection date for primary outcome measure)|
|Experimental: Imatinib Mesylate||
Drug: imatinib mesylate
Patients will receive treatment with imatinib mesylate at a dose of 600 mg by mouth once a day for 12 months. The study dose can be split but the dose of 600 mg must be given within a 12 hour period.
Other Name: GleevecGenetic: gene expression analysis
Multidrug resistance genes: These studies will include: MDR1, MRP1, LRP, and BCRP. Bone marrow blocks or cut slides will be sent to Duke on the diagnostic AML samples. DNA will be eluted from the samples so that the above genes can be analyzed.
Other Name: MRDGenetic: mutation analysis
FLT3 mutation analysis (on bone marrow aspirate or peripheral blood): These analyses will be performed by pathology at the time of diagnosis, at the participating institution. Samples will be analyzed for the FLT3 ITD and/or D835 mutation by PCR.
Other Name: FLT3Genetic: polymerase chain reaction
AF1q gene analysis (on bone marrow aspirate)
Other Name: AF1Q gene analysisOther: flow cytometry
C-kit MFI on AML samples will be calculated by using a CD45/ orthogonal light scatter gate to isolate blasts. The MFI will be calculated as the c-kit mean channel number (MCN) of the blasts/ MCN auto fluorescence.
Other Name: C-kit MFI, CD117Procedure: biopsy
Diagnostic bone marrow biopsy/aspirate must be done within 3 weeks of registration documenting complete remission
Other Name: bone marrow biopsy/aspirate
- To determine whether adding imatinib mesylate as maintenance therapy improves progression-free survival in patients with c-kit positive acute myeloid leukemia (AML) compared with historical controls.
- To assess the feasibility of administering imatinib mesylate as maintenance therapy after the completion of induction and consolidation therapy in these patients.
- To evaluate potential mechanisms of relapse/resistance in c-kit positive AML by examining multidrug resistance gene expression and AF1q gene expression and to determine whether these levels correlate with c-kit expression.
OUTLINE: This is a multicenter study.
Patients receive oral imatinib mesylate once daily for up to 12 months.
Bone marrow and peripheral blood are collected at baseline. Laboratory endpoints are evaluated by flow cytometry; mutation and gene analysis by PCR.
|United States, New York|
|Roswell Park Cancer Institute|
|Buffalo, New York, United States, 14263|
|United States, North Carolina|
|Duke University Medical Center|
|Durham, North Carolina, United States, 27710|
|United States, Ohio|
|Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center|
|Cleveland, Ohio, United States, 44106-5065|
|Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center|
|Cleveland, Ohio, United States, 44195|
|Principal Investigator:||Anjali Advani, MD||Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center|
|Principal Investigator:||Brenda Cooper, MD||Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center|