Trial Information

A Phase III Trial To Evaluate The Safety And Efficacy Of Specific Immunotherapy, Recombinant Idiotype Conjugated To KLH With GM-CSF, Compared To Non-Specific Immunotherapy, KLH With GM-CSF, In Patients With Follicular Non-Hodgkin's Lymphoma

OBJECTIVES:

- Compare the time to tumor progression in patients with stage III or IV follicular
B-cell non-Hodgkin's lymphoma treated with cyclophosphamide, prednisone, and
vincristine followed by immunotherapy with keyhole limpet hemocyanin with or without
autologous tumor-derived immunoglobulin idiotype and adjuvant sargramostim (GM-CSF).

- Compare the efficacy of these immunotherapy regimens in terms of converting patients
with partial response or unconfirmed complete response to clinical complete response.

- Compare the safety and toxic effects of these immunotherapy regimens in this patient
population.

- Compare the time to treatment failure and survival of patients treated with these
regimens.

- Correlate the induction of idiotype-specific immune response with clinical benefits of
achieving molecular remission in these patients.

- Compare the quality of life of patients treated with these regimens.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study.

Patients receive cyclophosphamide IV over 30-40 minutes and vincristine IV on day 1.
Patients also receive oral prednisone on days 1-5. Treatment repeats every 21 days for 8
courses.

At 6 months after completion of chemotherapy, patients maintaining partial response (PR),
complete response (CR), or unconfirmed complete response (CRU) receive immunotherapy.
Patients are stratified according to participating center and baseline disease status (PR vs
CR/CRU). Patients are randomized to one of two treatment arms.

- Arm I: Patients receive autologous tumor-derived immunoglobulin idiotype conjugated to
keyhole limpet hemocyanin (KLH) subcutaneously (SC) on day 1 and adjuvant sargramostim
(GM-CSF) SC on days 1-4 of weeks 0, 4, 8, 12, 16, 20, and 24.

- Arm II: Patients receive KLH alone SC on day 1 and GM-CSF SC on days 1-4 of weeks 0, 4,
8, 12, 16, 20, and 24.

Quality of life is assessed prior to first immunization, at 2-8 weeks after completion of
immunizations, and then every 6 months for 30 months.

Patients are followed every 3 months for 1 year and then every 6 months thereafter. Patients
also enroll in a long-term follow-up study for an additional 5 years.

PROJECTED ACCRUAL: A total of 360 patients (240 in arm I and 120 in arm II) will be accrued
from the 480 patients biopsied for this study within 15-18 months.