Patient case: 13-year-old male with acute myeloid leukemia; genetic feature: FLT3

Clinical trial: Imatinib Mesylate in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia Who Have Received Chemotherapy

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.

Detailed 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.

Eligibility: 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.

Relevance to patient case: not relevant