Trial Information

A Phase II Trial of Sequential Chemotherapy, Imatinib Mesylate (Gleevec, STI571) (NSC # 716051, IND #61135), and Transplantation for Adults With Newly Diagnosed Ph+ Acute Lymphoblastic Leukemia by the CALGB and SWOG

PRIMARY OBJECTIVES:

I. Determine the activity of imatinib mesylate (Gleevec) to prolong disease-free survival
(DFS) and overall survival in ALL patients with t(9;22).

II. Determine the ability of imatinib mesylate (Gleevec) to produce or maintain a
BCR-ABL-negative status, as judged by RT-PCR following sequential chemotherapy, imatinib
mesylate (Gleevec) and transplantation.

III. Determine the feasibility of collecting adequate peripheral blood stem cells for
autologous transplantation following imatinib mesylate (Gleevec) therapy.

IV. Study the safety and efficacy of autologous peripheral stem cell transplantation
following therapy with imatinib mesylate (Gleevec).

V. Study the safety and efficacy of allogeneic stem cell transplantation following therapy
with imatinib mesylate (Gleevec).

VI. Study the safety and efficacy of imatinib mesylate (Gleevec) administered after
allogeneic or autologous stem cell transplant.

OUTLINE: This is a multicenter study.

COURSE I (remission induction): Patients receive 1 course of front-line induction therapy on
a CALGB/SWOG protocol prior to enrollment.

COURSE II (imatinib mesylate): Patients receive imatinib mesylate orally (PO) twice daily on
days 1-28.

COURSE III (CNS prophylaxis): Within 7 days after completing course II, patients receive
methotrexate intrathecally (IT), methotrexate intravenously (IV) over 3 hours, and
vincristine sulfate IV on days 1, 8, and 15; methotrexate PO every 6 hours on days 1-2, 8-9,
and 15-16; leucovorin calcium IV on days 2, 9, and 16; and leucovorin calcium PO every 6
hours on days 3, 4, 10, 11, 17, and 18.

COURSE IV (imatinib mesylate): After blood counts recover after completion of course III,
patients receive imatinib mesylate as in course II.

COURSE V: Patients undergo allogeneic peripheral blood stem cell transplantation (PBSCT),
autologous PBSCT, or no PBSCT.

COURSE Va (allogeneic PBSCT for patients with HLA-matched sibling donor): Beginning 3-10
days after completion of course IV, patients with an HLA-matched sibling donor undergo total
body irradiation (TBI) 2-3 times daily on days -7 to -4. Patients receive etoposide IV over
4 hours on day -3. Patients then undergo PBSCT on day 0. Patients then receive graft-vs-host
disease prophylaxis with tacrolimus IV continuously on days -1 to 56 (or IV continuously on
days -1 to 14 and then PO or IV every 12 hours on days 15-56) followed by a taper. Patients
also receive methotrexate IV on days 1, 3, and 6, and filgrastim (G-CSF) subcutaneously (SC)
beginning on day 4 and continuing until blood counts recover.

COURSE Vb (autologous PBSCT for patients without HLA-matched sibling donor): Beginning 3-10
days after completion of course IV, patients without an HLA-matched sibling donor receive
etoposide IV continuously and cytarabine IV over 2 hours on days 1-4. Patients also receive
G-CSF SC beginning on day 14 and continuing until PBSC collection is complete. Patients
receive imatinib mesylate PO twice daily beginning after completion of PBSC collection and
continuing until 3 days before PBSCT. Patients then undergo TBI 2-3 times daily on days -8
to -5. Patients receive etoposide IV over 4 hours on day -4 and cyclophosphamide IV over 2
hours on day -2. Patients undergo PBSCT on day 0. Patients receive G-CSF SC beginning on day
0 and continuing until blood counts recover.

COURSE Vc (no transplantation for patients who are not transplant candidates): Beginning
3-10 days after completion of course IV, patients who are not candidates for PBSCT receive
etoposide IV over 4 hours and cytarabine IV over 2 hours on days 1-4. Patients also receive
G-CSF SC once or twice a day beginning on day 14 and continuing until blood counts recover.

COURSE VI: Patients receive imatinib mesylate PO once or twice daily beginning on day 30
post transplantation or on day 30 if no transplantation received and continuing for at least
1 year or until patient has 2 consecutive negative reverse transcriptase-polymerase chain
reaction assays at least 3 months apart or until relapse.

After completion of study treatment, patients are followed up monthly for 1 year, every 3
months for 2 years, every 6 months for 2 years, then yearly for up to 10 years.