Trial Information

TREATMENT OF ADULT ACUTE LYMPHOBLASTIC LEUKEMIA: PHASE II TRIALS OF AN INDUCTION REGIMEN INCLUDING PEG-L-ASPARAGINASE, WITH OR WITHOUT PIXY, IN PREVIOUSLY UNTREATED PATIENTS, FOLLOWED BY ALLOGENEIC BONE MARROW TRANSPLANTATION OR FURTHER CHEMOTHERAPY IN FIRST COMPLETE REMISSION

OBJECTIVES: I. Evaluate if front line induction therapy with daunorubicin, vincristine,
prednisone, and asparaginase is sufficiently effective to warrant a phase III trial in
patients with acute lymphocytic leukemia (ALL). II. Assess the toxicity of this regimen in
this patient population. III. Assess disease free and overall survival and toxicity
associated with allogeneic bone marrow transplantation for ALL patients in first remission
following induction and consolidation therapy. IV. Assess disease free and overall survival
and toxicity associated with sequential regimens of mercaptopurine, methotrexate and
vincristine, doxorubicin, dexamethasone, and cyclophosphamide, thioguanine, and cytarabine
in ALL patients in first remission who are ineligible for allogeneic bone marrow
transplantation. V. Evaluate the prognostic significance of cell surface immunophenotype,
Philadelphia chromosome, and polymerase chain reaction detected BCR/abl fusion in this
patient population.

OUTLINE: Patients are stratified according to age (15 to 29 vs 30 to 49 vs 50 to 65),
performance status (0-1 vs 2-3), participating center, and candidate for allogeneic bone
marrow transplantation (yes vs no). Patients receive induction chemotherapy consisting of
daunorubicin IV on days 1-3, vincristine IV on days 1, 8, 15, and 22, oral prednisone on
days 1-28, and asparaginase IV or intramuscularly (IM) on days 15-24. Patients with
persistent leukemia on day 21, receive additional induction therapy consisting of
daunorubicin IV on days 22 and 23, vincristine IV on days 29 and 36, and oral prednisone
continuing to day 42. Patients with CNS leukemia receive additional therapy beginning on day
1 of induction chemotherapy consisting of methotrexate intrathecally (IT) or
intraventricularly twice weekly until blasts are absent in spinal fluid. Patients receive
oral leucovorin calcium every 6 hours for a total of 4 doses following each IT dose in the
absence of blood count recovery. Following absence of spinal fluid blasts, patients receive
methotrexate IT or intraventricularly weekly for 4 weeks then monthly for 1 year. Patients
also receive cranial radiotherapy during consolidation therapy 5 days a week for 2.5 weeks.
Patients with A1 bone marrow receive consolidation therapy following completion of induction
therapy and blood count recovery. Patients receive consolidation therapy consisting of
cyclophosphamide IV on days 1, 15, and 29, cytarabine IV on days 2-5, 9-12, 16-19, and
23-26, oral mercaptopurine on days 1-28, and methotrexate IT on days 2, 9, 16, and 23.
Following completion of consolidation therapy, patients eligible for allogeneic bone marrow
transplantation receive total body radiotherapy 3 times a day on days -7, -6, -5, and twice
on day -4, and eptoposide IV over 4 hours on day -3. Patients undergo allogeneic bone marrow
transplantation on day 0. Following completion of consolidation therapy, patients ineligible
for allogeneic bone marrow transplantation receive maintenance therapy consisting of oral
mercaptopurine on days 1-63, and oral methotrexate on days 1, 8, 15, 22, 29, 36, 43, 50, and
57. Patients receive subsequent courses of maintenance therapy when blood counts recover.
Patients receive a second course of maintenance therapy consisting of vincristine IV on days
1, 8, 15, and 22, doxorubicin IV on days 1, 8, 15, and 22, and oral dexamethasone on days
1-28. Patients receive a third course consisting of cyclophosphamide IV on day 1, oral
thioguanine on days 1-14, and cytarabine IV on days 3-6 and 10-13. Patients receive a fourth
course consisting of oral mercaptopurine and oral methotrexate daily for 2 years. Patients
are followed monthly for 6 months and then every 2 months thereafter.

PROJECTED ACCRUAL: A total of 25-50 patients will be accrued for this study.