Study of the BiovaxId Tumor Derived Idiotype Vaccine in Patients With Follicular Lymphoma (BiovaxID)

Randomized Trial of Patient-Specific Vaccination With Conjugated Follicular Lymphoma-Derived Idiotype (FNHLId1) With Local GM-CSF in First Complete Remission

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.

follicular, lymphoma, Non-Hodgkins, idiotype, vaccine, indolent follicular Non-Hodgkins Lymphoma, tumor-derived, B-cell, cancer

5 monthly vaccinations over a 6 month time period consisting of 0.5 mg ID-KLH s.c. on day 1 and 100 mcg/m²/day GM-CSF s.c. on days 1-4

5 monthly vaccinations at month 1, 2, 3, 4, and 6 consisting of 0.5 mg KLH s.c on day 1 and 100 mcg/m²/day GM-CSF s.c. on days 1-4

To demonstrate prolongation of the period of Disease Free Survival (significant prolongation of the period of complete remission) in idiotype vaccine treated patients

To assess the ability of the idiotype vaccine to generate an immunologic response against the NHL tumor

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

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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. doi: 10.1056/NEJM199210223271705.

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Schuster SJ, Neelapu SS, Gause BL, Janik JE, Muggia FM, Gockerman JP, Winter JN, Flowers CR, Nikcevich DA, Sotomayor EM, McGaughey DS, Jaffe ES, Chong EA, Reynolds CW, Berry DA, Santos CF, Popa MA, McCord AM, Kwak LW. Vaccination with patient-specific tumor-derived antigen in first remission improves disease-free survival in follicular lymphoma. J Clin Oncol. 2011 Jul 10;29(20):2787-94. doi: 10.1200/JCO.2010.33.3005. Epub 2011 May 31.