Trial Information

Gleevec (Imatinib) Plus Multi-Agent Chemotherapy For Newly-Diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia

OBJECTIVES:

Primary

- To determine the clinical efficacy of imatinib mesylate and combination chemotherapy in
terms of complete response (CR) rate (both hematologic and molecular), CR duration, and
overall survival in patients with newly diagnosed Philadelphia chromosome-positive
acute lymphoblastic leukemia.

- To determine the toxicities of this regimen in these patients.

Secondary

- To establish the prognostic factors in patients treated with this regimen.

OUTLINE: This is a multicenter study. Patients are stratified according to age (64 or less
vs 65 or over).

- Induction chemotherapy: Patients receive daunorubicin hydrochloride IV continuously
over 24 hours on days 1-3, vincristine IV on days 1 and 8, and oral prednisolone on
days 1-14. Treatment repeats for 5 courses in the absence of disease progression or
unacceptable toxicity.

- Imatinib mesylate administration: Patients also receive oral imatinib mesylate once
daily beginning on day 8 of course 1 induction chemotherapy and continuing for up to 2
years.

- Consolidation chemotherapy: Patients receive daunorubicin hydrochloride IV continuously
over 24 hours on days 1-2, vincristine IV on days 1 and 8, and oral prednisolone on
days 1-14 in course 1; cytarabine IV over 2 hours and etoposide IV over 3 hours on days
1-4 in courses 2 and 4; and methotrexate IV continuously over 36 hours on days 1-2 and
15-16 and leucovorin calcium IV every 6 hours x 3 doses followed by oral leucovorin
calcium until methotrexate levels are < 0.05 micromol/L in courses 3 and 5. Treatment
continues in the absence of disease progression or unacceptable toxicity. Patients with
available HLA-matched sibling or unrelated hematopoietic cell donors or
HLA-nonidentical familial hematopoietic cell donors proceed to allogeneic hematopoietic
stem cell transplantation (HSCT). Patients who are without hematopoietic cell donors
and who remain in hematologic remission continue to receive maintenance therapy with
oral imatinib mesylate.

- Allogeneic HSCT: Patients undergo HSCT.

- CNS prophylaxis: Patients receive six doses of intrathecal (IT) methotrexate and
hydrocortisone beginning on the first day of each chemotherapy course. Patients with
CNS disease at diagnosis receive intensified CNS therapy comprising 10 doses of IT
methotrexate and cranial irradiation after bone marrow remission is achieved.

After completion of study treatment, patients are followed periodically.