Imatinib Mesylate in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia Who Have Received Chemotherapy
Condition: Leukemia
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
Intervention: imatinib mesylate; gene expression analysis; mutation analysis; polymerase chain reaction; flow cytometry; biopsy
Intervention description: 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.; 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.; 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.; AF1q gene analysis (on bone marrow aspirate); 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.; Diagnostic bone marrow biopsy/aspirate must be done within 3 weeks of registration documenting complete remission
Intervention MeSH terms: Imatinib Mesylate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 32.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: adult acute minimally differentiated myeloid leukemia (M0); adult acute myeloblastic leukemia with maturation (M2); adult acute myeloblastic leukemia without maturation (M1); adult acute myeloid leukemia with 11q23 (MLL) abnormalities; adult acute myeloid leukemia with inv(16)(p13;q22); adult acute myeloid leukemia with t(16;16)(p13;q22); adult acute myeloid leukemia with t(8;21)(q22;q22); adult acute myelomonocytic leukemia (M4); adult acute megakaryoblastic leukemia (M7); adult acute monoblastic leukemia (M5a); adult acute monocytic leukemia (M5b); adult erythroleukemia (M6a); adult pure erythroid leukemia (M6b); adult acute basophilic leukemia; adult acute eosinophilic leukemia; adult acute myeloid leukemia in remission

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.
    

Eligibility criteria:

        INCLUSION CRITERIA

          -  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 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 ≥ 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.