Vaccine Therapy and GM-CSF in Treating Patients With CNS Lymphoma

OBJECTIVES:

Primary

- To determine the proportion of patients with CNS lymphoma who develop anti-idiotype (Id)
and anti-keyhole limpet hemocyanin (KLH) humoral immune responses in the serum and/or
CSF following patient-specific immunotherapy comprising recombinant tumor-derived
immunoglobulin Id-KLH conjugate vaccine and sargramostim (GM-CSF).

- To assess the safety and tolerability of this regimen in these patients.

Secondary

- To evaluate the progression-free survival (PFS) of patients treated with this regimen.

- To determine the time to receipt of first subsequent anti-lymphoma therapy after
initiating immunization with the Id-KLH conjugate vaccine.

- To assess the correlation of anti-Id immune response in the CSF and/or serum with PFS
and overall survival.

Tertiary

- To evaluate the kinetics of humoral immune response development in patients treated with
this regimen.

OUTLINE:

- Pre-immunotherapy: Patients submit a tumor sample for manufacturing of the idiotype
(Id)-keyhole limpet hemocyanin (KLH) conjugate vaccine and undergo placement of an
Ommaya reservoir. Patients then receive induction therapy comprising methotrexate IV
once every 2 weeks until a maximum radiographic response is achieved, as assessed by MRI
of the brain. Patients then receive methotrexate IV once a month for 6 months. Patients
with leptomeningeal or CSF involvement also receive intraventricular thiotepa twice a
week until the CSF is clear on three evaluations and then once a week until the CSF is
clear on four evaluations. Patients under 55 years of age also undergo whole brain
radiotherapy (or craniospinal radiotherapy when extensive leptomeningeal disease is
present). Patients who achieve a stable response to induction therapy proceed to
immunotherapy.

- Immunotherapy: Patients receive recombinant tumor-derived immunoglobulin Id-KLH
conjugate vaccine subcutaneously (SC) on day 1 of weeks 0, 2, 4, 6, 8, 10, 12, 16, 20,
24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, and 76. Patients also receive
sargramostim (GM-CSF) SC on days 1-4 of the same weeks as the Id-KLH conjugate vaccine.

After completion of therapy, patients are followed periodically for up to 2 years.

DISEASE CHARACTERISTICS:

- Histologically or CSF cytologically confirmed CNS lymphoma with any of the following
clinical histories:

- Primary CNS lymphoma at initial diagnosis

- Primary CNS lymphoma at relapse

- Systemic lymphoma with CNS disease at initial diagnosis or at relapse

- Adequate fresh tissue or cell pellet available for analysis by Genitope Corporation to
determine adequacy for idiotype (Id) manufacturing

- Tumor must express both functional light and heavy chain genes

- No tumors known or found to be surface immunoglobulin negative

- Not in leukemic phase (i.e., > 5,000/mm³ circulating tumor cells)

PATIENT CHARACTERISTICS:

- ECOG performance status (PS) 0-2 OR Karnofsky PS 70-100%

- WBC ≥ 1,500/mm³

- Platelet count ≥ 75,000/mm³

- Hemoglobin ≥ 10 g/dL

- Serum bilirubin ≤ 1.5 times upper limit of normal (ULN) (unless due to Gilbert's
disease)

- Creatinine ≤ 1.5 times ULN

- Able to undergo placement of an Ommaya reservoir

- Able to receive induction therapy (chemotherapy with or without brain radiotherapy)
with intent to induce remission

- Speaks English or Spanish

- No other malignancy within the past 3 years, except adequately treated basal cell or
squamous cell carcinoma of the skin or cervical carcinoma in situ

- Not pregnant or nursing

- No immunosuppressive viral infections as evidenced by HIV antibody or antigen,
hepatitis B antigen, or hepatitis C antibody or antigen positivity

- No history of autoimmune disease that required treatment within the past 5 years,
including previously treated autoimmune hemolytic anemia or immune thrombocytopenia

PRIOR CONCURRENT THERAPY:

- More than 30 days since prior and no concurrent participation in another therapeutic
clinical trial

- More than 2 weeks since prior steroids

- No concurrent immunosuppressives, including corticosteroids

- Transient use of optical or nasal steroid solutions is allowed

- No other concurrent anticancer therapy or therapy for non-Hodgkin lymphoma