• Immune response rates in patients who received at least 4 immunizations by anti-idiotype antibody and anti-KLH antibody assays during every other immunization, last immunization, 2 and 8 weeks post immunization, and then quarterly for 1 year [ Designated as safety issue: No ]
• Clinical response in patients who received at least 1 immunization in groups I and II by modified Cheson criteria post-immunization and then every 6 months for 1 year [ Designated as safety issue: No ]
• Safety at the start of immunization, every 8 weeks during immunization, 2 and 8 weeks post immunization, and then quarterly for 1 year [ Designated as safety issue: Yes ]

• Immune response rates in patients who received at least 4 immunizations by anti-idiotype antibody and anti-KLH antibody assays during every other immunization, last immunization, 2 and 8 weeks post immunization, and then quarterly for 1 year
• Clinical response in patients who received at least 1 immunization in groups I and II by modified Cheson criteria post-immunization and then every 6 months for 1 year
• Safety at the start of immunization, every 8 weeks during immunization, 2 and 8 weeks post immunization, and then quarterly for 1 year

RATIONALE: Monoclonal antibodies such as rituximab can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Vaccines made from a person's cancer cells may make the body build an immune response to kill cancer cells. Colony-stimulating factors such as sargramostim may increase the number of immune cells found in bone marrow or peripheral blood.

PURPOSE: Phase II trial to study the effectiveness of rituximab followed by vaccine therapy and sargramostim in treating patients who have refractory or progressive non-Hodgkin's lymphoma.

OBJECTIVES:

• Determine progression-free survival in patients with refractory or progressive follicular non-Hodgkin's lymphoma treated with immediate or delayed autologous immunoglobulin idiotype-KLH conjugate vaccine and sargramostim after rituximab (groups I and II).
• Determine the immune response rate in patients treated with these regimens (groups I, II, and III).
• Determine the safety and toxicity of these regimens in these patients (groups I, II, and III).

OUTLINE: This is an open-label, multicenter study for patients previously registered on and confirmed ineligible for randomization in protocol Genitope-G2000-03.

Patients receive rituximab IV weekly for 4 weeks.

• Group I: The first 30 patients to achieve and maintain a partial response (PR) or better receive autologous immunoglobulin idiotype-KLH conjugate vaccine subcutaneously (SC) on day 1 and sargramostim SC on days 1-4 beginning 26 weeks after the last dose of rituximab. Treatment repeats every 2 weeks for 14 weeks (8 immunizations).
• Group II: All subsequent patients who achieve a PR or better receive autologous immunoglobulin idiotype-KLH conjugate vaccine and sargramostim SC as in group I beginning 13 weeks after the last dose of rituximab.
• Group III: Patients who are not eligible for group I or II and, in the investigator's opinion, are suitable candidates for immunization with autologous immunoglobulin idiotype-KLH conjugate vaccine and sargramostim SC receive the same treatment as groups I and II, beginning no more than 1 year after the last (fourth) dose of rituximab.

In all groups, treatment continues in the absence of unacceptable toxicity or emergence of an illness that may interfere with study assessments.

Patients are followed for initial response 8 weeks after completion of immunizations and then every 12 weeks for an additional year. Thereafter, all immunized patients will be followed every 6 months until receipt of first subsequent anti-lymphoma therapy.

PROJECTED ACCRUAL: Up to 120 patients will be accrued for this study.

• Biological: autologous immunoglobulin idiotype-KLH conjugate vaccine
• Biological: sargramostim

DISEASE CHARACTERISTICS:

• Histologically confirmed follicular center cell non-Hodgkin's lymphoma
• Stage III or IV disease at time of entry on Genitope-G2000-03
• At least 1 bidimensionally measurable lesion (1.5 cm X 1.5 cm) by radiography
• Previously registered on and confirmed to be ineligible for randomization on Genitope-G2000-03 by failing to achieve or maintain a complete or partial response after chemotherapy by CT scans of the chest, abdomen, and pelvis (and neck if there was palpable disease)
• Completed all 8 courses of chemotherapy (cyclophosphamide, vincristine, and prednisone [CVP]) per Genitope-G2000-03
• No intervening therapy for lymphoma (i.e., antibody, corticosteroids, or cytotoxic) between CVP and study entry
• No evidence of transformation (e.g., rapid tumor growth or increasing lactic dehydrogenase)
• No CNS involvement

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-1

Life expectancy

• Not specified

Hematopoietic

• Not specified

Hepatic

• Not specified

Renal

• Not specified

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 6 months after the last immunization series
• HIV negative
• No history of autoimmune disease or conditions requiring treatment with immunosuppressive agents, including corticosteroids
• No other malignancy within the past 2 years except non-basal cell skin cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

Biologic therapy

• See Disease Characteristics

Chemotherapy

• See Disease Characteristics

Endocrine therapy

• See Disease Characteristics
• At least 6 months since prior corticosteroids, including topical administration for any concurrent disease

• No concurrent chronic (more than twice monthly) corticosteroids (including topical or inhaled)

  • Transient use (prior to CT scan) or optical solutions allowed

Radiotherapy

• Prior radiotherapy to no more than 2 sites more than 13 weeks before rituximab is allowed

Surgery

• Not specified

Other

• No concurrent participation in other therapeutic clinical trials