Combination Chemotherapy in Treating Patients With Non-Hodgkin's Lymphoma or Acute Lymphocytic Leukemia

OBJECTIVES:

• Determine if increasing the methotrexate dose in combination with standard treatment is feasible in patients with advanced small noncleaved cell non-Hodgkin's lymphoma or B-cell acute lymphocytic leukemia.
• Assess the toxicity of this intensified therapy in these patients.
• Assess the feasibility of treating these patients that have CNS disease at diagnosis with this intensified therapy plus etoposide and ifosfamide.
• Assess toxicities and late effects of this intensive therapy on the central nervous system, cardiac function, and fertility in these patients.

OUTLINE: This is a multicenter study. Patients are stratified according to stage and disease (stage III non-Hodgkin's lymphoma (NHL) vs stage IV NHL with no CNS involvement vs stage IV NHL with CNS involvement vs B-cell acute lymphocytic leukemia (B-ALL) with no CNS involvement vs B-ALL with CNS involvement).

Patients receive methotrexate and cytarabine intrathecally on days 1, 4, 11, and 36 (on day 40 for patients with stage IV NHL or B-ALL only) in combination with alternating courses of: A) cyclophosphamide IV every 12 hours for a total of six doses on days 1-3, doxorubicin IV over 30 minutes on day 4, vincristine IV on days 4 and 11, dexamethasone IV or orally twice daily on days 1-5, and filgrastim (G-CSF) subcutaneously (SQ) or IV over 30 minutes beginning on day 5 and continuing until blood counts recover and B) methotrexate IV over 24 hours on day 18, methotrexate intrathecally on day 18, dexamethasone IV or orally twice daily on days 18-22, leucovorin calcium IV or orally every 6 hours for a total of 6 doses on days 20-21, cytarabine IV over 48 hours on days 20-21, and G-CSF SQ or IV over 30 minutes beginning on day 22 and continuing until blood counts recover. Patients with stage III NHL receive at total of 5 courses of treatment (A-B-A-B-A) and patients with stage IV NHL or B-ALL with no CNS involvement receive a total of 6 courses of treatment (A-B-A-B-A-B).

Patients with CNS involvement receive a third course of treatment: C) etoposide IV over 1 hour on days 36-40, ifosfamide IV over 1 hour on days 36-40, oral dexamethasone twice daily on days 36-40, and G-CSF SQ or IV over 30 minutes beginning on day 41 and continuing until blood counts recover. Patients with CNS involvement receive a total of 7 courses of treatment (A-B-C-A-B-A-B).

Patients are followed every 6 months for 4 years and then annually thereafter.

PROJECTED ACCRUAL: A total of 27-80 patients will be accrued for this study over 24 months.

DISEASE CHARACTERISTICS:

• One of the following diagnoses:

• Histologically confirmed small noncleaved cell non-Hodgkin's lymphoma

• Stage III or IV
• Burkitt's or non-Burkitt's by the Working Formulation OR
• Burkitt's or Burkitt's-like by the REAL classification
• Histologically confirmed B-cell acute lymphocytic leukemia

• At least 25% blasts in bone marrow
• FAB L3 morphology
• FAB L1 morphology allowed if blasts show B-cell markers (CD19, 20, 22) and surface immunoglobulin positivity
• Must be registered on POG-9900 in past 8 days

PATIENT CHARACTERISTICS:

Age:

• Under 22 at time of diagnosis

Performance status:

• Not specified

Life expectancy:

• Not specified

Hematopoietic:

• Not specified

Hepatic:

• Not specified

Renal:

• Not specified

Other:

• Not pregnant or nursing
• Negative pregnancy test
• HIV positive allowed

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• Not specified

Endocrine therapy:

• No concurrent use of dexamethasone as antiemetic

Radiotherapy:

• Not specified

Surgery:

• Prior surgery allowed

Other:

• No prior therapy except surgery