Trial Information

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

OBJECTIVES: I. Evaluate the feasibility and toxicity of dose intensification of methotrexate
and cyclophosphamide in patients with stage III or IV small, noncleaved cell non-Hodgkin's
lymphoma or B cell acute lymphoblastic leukemia. II. Estimate the response rate and survival
of these patients after this therapy.

OUTLINE: This is a two-stage study. Patients will receive cytarabine either by continuous
infusion (first stage) or bolus injection (second stage). Patients are stratified by disease
(stage III non-Hodgkin's lymphoma (NHL) vs stage IV NHL vs stage B acute lymphoblastic
leukemia). Therapy for all patients consists of alternating courses of "A" and "B". Patients
with stage III disease receive 4 courses of chemotherapy (ABAB) while those with stage IV
disease and B cell acute lymphoblastic leukemia receive 6 chemotherapy courses (ABABAB).
Course A - Induction: Patients receive intrathecal methotrexate (IT MTX) and intrathecal
cytarabine (IT Ara-C) on days 1, 4, and 11. Dexamethasone is administered by IV or orally
twice a day on days 1-5. Cyclophosphamide IV is administered every 12 hours on days 1-3.
Doxorubicin IV is administered over 15 minutes beginning 12 hours after the beginning of the
6th dose of cyclophosphamide (day 4). At the same time, vincristine IV is administered, then
repeated on day 11. Patients begin filgrastim (granulocyte colony-stimulating factor; G-CSF)
subcutaneously or IV over 30 minutes on day 5. Course B - Induction: The first 10 patients
enrolled receive cytarabine by continuous infusion while the second 10 patients enrolled
receive cytarabine by bolus IV. Patients begin treatment on day 18 and receive methotrexate
IV over 24 hours plus IT MTX during hour 1. Dexamethasone is administered by IV or orally
twice a day on days 1-5. After completing the 24 hour IV MTX infusion, patients begin
cytarabine by continuous infusion over 48 hours or bolus IV every 12 hours for 4 doses.
Patients receive G-CSF subcutaneously or IV over 30 minutes beginning on day 22. Patients
are assessed for remission status before day 36. Course A - Consolidation: Patients receive
dexamethasone IV or orally twice a day on days 1-5. IT MTX and IT Ara-C are administered on
days 1 and 4. Cyclophosphamide is administered as during Induction, with vincristine IV and
doxorubicin IV over 15 minutes 12 hours later. Vincristine repeats 1 week later. G-CSF
administration begins on day 5. Course B - Consolidation: Therapy begins on day 22 with
dexamethasone administered as previously. Methotrexate infusion and IT MTX are administered
as in Course B - Induction, as is cytarabine (either as a continuous infusion or bolus IV).
G-CSF is also administered as previously. Patients are followed monthly for the first 6
months, every 2 months for the next 6 months, then every 6 months for 3 years, then annually
thereafter.

PROJECTED ACCRUAL: A total of 20 patients will be accrued for this study within 16 months.