Trial Information

Phase II Study in Adults With Untreated Acute Lymphoblastic Leukemia Testing Increased Doses of Daunorubicin During Induction, and Cytarabine During Consolidation, Followed by High-Dose Methotrexate and Intrathecal Methotrexate in Place of Cranial Irradiation

OBJECTIVES:

- Determine the complete response rate and toxicity of escalating doses of daunorubicin
in patients under 60 years old with untreated acute lymphoblastic leukemia (ALL).

- Determine the complete response rate and toxicity of a constant dose of daunorubicin in
patients at least 60 years old with untreated ALL.

- Determine the toxicity of high dose cytarabine during postremission therapy in these
patients.

- Determine the CNS relapse rate of ALL when prophylactic intrathecal methotrexate and
high-dose intravenous chemotherapy replace cranial irradiation.

OUTLINE:

- Course I: Patients are assigned to 1 of 2 induction treatment groups based on age.

- Group 1 (under age 60): Patients receive cyclophosphamide IV over 15-30 minutes on
day 1, escalating doses of daunorubicin IV over 5-10 minutes on days 1-3,
vincristine IV on days 1, 8, 15, and 22, oral prednisone on days 1-21,
asparaginase intramuscularly on days 5, 8, 11, 15, 18, and 22, and filgrastim
(G-CSF) subcutaneously (SC) beginning on day 4 and continuing for at least 7 days
and then until blood counts recover.

- Group 2 (age 60 and over): Patients receive vincristine, asparaginase,
cyclophosphamide, and G-CSF as in group 1, fixed dose daunorubicin IV over 5-10
minutes on days 1-3, and oral prednisone on days 1-7.

Patients are then evaluated for bone marrow cellularity on day 29. Those with M0, M1, or M2
cellularity proceed to course II. Patients with M3 cellularity may proceed to course II or
be removed from study.

- Course II (early intensification): Patients receive intrathecal methotrexate and
cyclophosphamide IV over 15-30 minutes on day 1, cytarabine IV over 3 hours on days
1-3, and G-CSF SC beginning on day 4.

Bone marrow is again examined on day 29. Patients with M0 or M1 cellularity after course I
and no sign of relapse after course II proceed to course III. Patients with M2 or M3
cellularity after course I must have M0 or M1 cellularity after course II to proceed to
course III. Patients with M2 or M3 cellularity after course II are removed from study.

- Course III: Patients receive intrathecal methotrexate, vincristine IV, and methotrexate
IV over 3 hours on days 1, 8, and 15 and oral methotrexate every 6 hours for 4 doses
beginning 6 hours after starting methotrexate IV on days 1, 2, 8, 9, 15, and 16.
Patients receive leucovorin calcium IV 6 hours after the last oral methotrexate dose on
days 2, 9, and 16 and oral leucovorin calcium beginning 12 hours after leucovorin
calcium IV for at least 4 doses on days 3, 4, 10, 11, 17, and 18.

Patients must be off leucovorin calcium for a minimum of 3 days before beginning days 8 and
15 of treatment. Patients who maintain M0 or M1 cellularity on day 29 of course III continue
therapy. Those with M2 or M3 cellularity after course III are removed from the study.

- Course IV (Late intensification): Repeat course I.

- Course V (Late intensification): Repeat course II.

- Course VI (CNS intensification): Repeat course III.

- Course VII (Prolonged maintenance): Patients receive oral mercaptopurine daily,
vincristine IV once every 4 weeks, oral prednisone on days 1-5, and oral methotrexate
on days 1, 8, 15, and 22. Courses repeat every 4 weeks for up to 18 months.

Patients with testicular disease receive gonadal radiotherapy anytime after course I.
Chemotherapy is not halted during radiotherapy.

Patients are followed every 3 months for 1 year, every 6 months for 2 years, and then
annually for 10 years.

PROJECTED ACCRUAL: A total of 140 patients will be accrued for this study within 15 months.