Overview

This trial is active, not recruiting.

Condition leukemia
Treatments imatinib mesylate, gene expression analysis, mutation analysis, polymerase chain reaction, flow cytometry, biopsy
Phase phase 2
Sponsor Case Comprehensive Cancer Center
Collaborator National Cancer Institute (NCI)
Start date December 2008
End date April 2013
Trial size 32 participants
Trial identifier NCT00509093, AUS259, CASE4906, NCI-2010-01198, P30CA043703

Summary

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
imatinib mesylate Gleevec
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.
gene expression analysis MRD
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.
mutation analysis FLT3
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.
polymerase chain reaction AF1Q gene analysis
AF1q gene analysis (on bone marrow aspirate)
flow cytometry C-kit MFI, CD117
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.
biopsy bone marrow biopsy/aspirate
Diagnostic bone marrow biopsy/aspirate must be done within 3 weeks of registration documenting complete remission

Primary Outcomes

Measure
Progression-free survival for patients less than 60 years of age
time frame: 13 months after treatment
Progression-free survival for patients 60 years of age and older
time frame: 8 months after treatment

Secondary Outcomes

Measure
Toxicity as measured by NCI CTC v. 3.0
time frame: 24 months
Correlation of c-kit expression with multidrug resistance gene expression (MDR1, MRP1, LRP, and BCRP) and AF1q expression
time frame: 24 months

Eligibility Criteria

Male or female participants at least 18 years old.

INCLUSION CRITERIA - Age > 18. - Diagnostic bone marrow aspirate/ biopsy or peripheral blood confirming AML. - At the time of diagnosis, patients must have c-kit (also known as CD117) positive AML (20% or more of the blasts express c-kit[CD117]). - A flow scattergram (from the diagnostic AML specimen) must be available to calculate a c-kit MFI. - Patients must have received standard induction chemotherapy with ADE (cytarabine, daunorubicin, and etoposide) or with 7+3 (7 days of cytarabine continuous infusion and 3 days of an anthracycline (idarubicin, daunorubicin, or mitoxantrone). Patients with persistent leukemia on a Day 10-28 marrow may have received a second course of chemotherapy. - After the completion of induction therapy, patients must have attained a complete remission based on blood count recovery (neutrophil count > 1,000/µL, platelet count > 100,000/µL), and bone marrow aspirate and biopsy (< 5% myeloblasts). - For patients < 60 years of age, patients must have received at least 2 courses of post-remission therapy with at least intermediate dose (400 mg/m2/day). *Patients with t(8;21) or inversion 16 at the time of diagnosis must have received at least 2 courses of high dose cytarabine. For patients > or = 60 years of age, patients must have received 1 course of post-remission therapy (the type of chemotherapy will not be specified). - Patients must be registered on this study (maintenance Imatinib mesylate) within 60 days of the last dose of post-remission therapy. - A bone marrow aspirate and/or biopsy must be done within 3 weeks of registration documenting CR. - Women of childbearing potential and sexually active males must use an effective method of contraception. - Female patients of childbearing potential must have negative pregnancy test within 7 days before initiation of study drug dosing. Postmenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential. Male and female patients of reproductive potential must agree to employ an effective barrier method of birth control throughout the study and for up to 3 months following discontinuation of study drug. - ECOG Performance Status 0-2. - Creatinine must be < 1.5 x upper limit of normal. - Total bilirubin must be < 2 mg/dl and AST and ALT must be < 2 times the upper limit of normal. - Previous treatment-related toxicities must have resolved to < Grade 1 excluding alopecia. - Written, voluntary informed consent. EXCLUSION CRITERIA - Acute promyelocytic leukemia. - Patients with an autologous or allogeneic bone marrow transplant. - History of HIV. - Pregnant or breast-feeding. - Serious or poorly controlled medical conditions that would interfere with the protocol. - At the time of study entry, any medications which could significantly interact with imatinib mesylate (see Section 9.4) must be discontinued. - Patients with active extramedullary disease are not eligible. - Patient has received any other investigational agents within 28 days of first day of study drug dosing. - Patient is < 5 years free of another primary malignancy except: if the other primary malignancy is not currently clinically significant nor requiring active intervention, or if other primary malignancy is a basal cell skin cancer or a cervical carcinoma in situ. Existence of any other malignant disease is not allowed. - Patient with Grade III/IV cardiac problems as defined by the New York Heart Association Criteria. (i.e., congestive heart failure, myocardial infarction within 6 months of study) - Patient has known chronic liver disease (i.e., chronic active hepatitis, and cirrhosis). - Patient previously received radiotherapy to > or = 25 % of the bone marrow - Patient had a major surgery within 2 weeks prior to study entry. - Patient with any significant history of non-compliance to medical regimens or with inability to grant reliable informed consent.

Additional Information

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
Principal investigator Anjali Advani, MD
Description OBJECTIVES: Primary - 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. Secondary - 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.
Trial information was received from ClinicalTrials.gov and was last updated in February 2015.
Information provided to ClinicalTrials.gov by Case Comprehensive Cancer Center.