• To determine the ability of the idiotype vaccine to produce a molecular complete remission [ Time Frame: once subject achieves molecular CR ] [ Designated as safety issue: No ]
• To determine the impact of molecular disease free survival [ Time Frame: until relapse ] [ Designated as safety issue: No ]
• To assess the ability of the idiotype vaccine to generate an immunologic response against the NHL tumor [ Time Frame: varies ] [ Designated as safety issue: No ]
• To compare the overall survival of subjects randomized to receive either treatment [ Time Frame: minimum 5 years from last subject randomized ] [ Designated as safety issue: No ]
• To confirm the safety of 5 monthly injections of the vaccine with GM-CSF [ Time Frame: 4 days ] [ Designated as safety issue: Yes ]

• To determine the ability of the idiotype vaccine to produce a molecular complete remission
• To determine the impact of molecular disease free survival
• To assess the ability of the idiotype vaccine to generate an immunologic response against the NHL tumor
• To compare the overall survival of subjects randomized to receive either treatment
• To confirm the safety of 5 monthly injections of the vaccine with GM-CSF

The primary objective of this Phase 3 study is to definitively confirm the safety and efficacy of BiovaxId, an autologous tumor derived immunoglobulin idiotype vaccine, as measured by a significant prolongation of the period of disease free survival when administered to patients with indolent follicular Non-Hodgkin's Lymphoma (NHL) during their first complete remission.

Patients with Stage III-IV follicular lymphoma and tumor > 2cm (Stage II allowed if tumor > 5cm), previously untreated by other than local radiation, provide tumor material by tissue biopsy for production of a patient-specific Ig idiotype vaccine conjugated to the immunogenic protein KLH. After completing PACE or CHOP-R chemotherapy and achieving a complete remission, followed by a waiting period to reconstitute the immune system, patients who remain in remission randomized to the active treatment arm receive a series of 5 idiotype vaccinations accompanied by the immune stimulant GM-CSF. Patients randomized to the control arm receive a time-matched series of KLH injections also accompanied by GM-CSF. Patients are subsequently studied to observe their immune responses both to the non-specific immune stimulating agents and for the specific immune response to the vaccine. Patients are followed for a minimum of 4 years post-randomization or until relapse.

• Biological: tumor specific immune response
• Biological: control vaccine

• Hsu FJ, Caspar CB, Czerwinski D, Kwak LW, Liles TM, Syrengelas A, Taidi-Laskowski B, Levy R. Tumor-specific idiotype vaccines in the treatment of patients with B-cell lymphoma--long-term results of a clinical trial. Blood. 1997 May 1;89(9):3129-35.
• Bendandi M, Gocke CD, Kobrin CB, Benko FA, Sternas LA, Pennington R, Watson TM, Reynolds CW, Gause BL, Duffey PL, Jaffe ES, Creekmore SP, Longo DL, Kwak LW. Complete molecular remissions induced by patient-specific vaccination plus granulocyte-monocyte colony-stimulating factor against lymphoma. Nat Med. 1999 Oct;5(10):1171-7.
• Kwak LW, Campbell MJ, Czerwinski DK, Hart S, Miller RA, Levy R. Induction of immune responses in patients with B-cell lymphoma against the surface-immunoglobulin idiotype expressed by their tumors. N Engl J Med. 1992 Oct 22;327(17):1209-15.
• Dar MM, Kwak LW. Vaccination strategies for lymphomas. Curr Oncol Rep. 2003 Sep;5(5):380-6. Review.

Inclusion/Exclusion Criteria:

• Diagnosis of indolent follicular lymphoma(follicular small-cleaved cell, follicular mixed or follicular large cell with centrocytes) with surface IgM or IgG phenotype.
• Stage III-IV with lymph node > 2cm or Stage II with lymph node > 5 cm
• No prior chemotherapy other than local radiation (not greater than 2 sites)
• ECOG < 2
• Survival > 1 yr
• Serum creatinine < 1.5 mg/dl
• Bilirubin <1.5 mg/dl
• SGOT/SGPT < 3.5 ULN
• No HIV antibodies or HBV antigen
• Negative pregnancy screen (females)
• No unrelated neoplasm in the previous 10 years
• No evidence of primary or secondary CNS lymphoma