Trial Information

A Pilot Study of Dose Intensification of Methotrexate in Patients With Advanced-Stage (III/IV) Small Non-Cleaved Cell Non-Hodgkins Lymphoma and B-Cell All

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.