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

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.

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.