Clinical trial NCT00091676: Study of the BiovaxId Tumor Derived Idiotype Vaccine in Patients With Follicular Lymphoma
Official title: Randomized Trial of Patient-Specific Vaccination With Conjugated Follicular Lymphoma-Derived Idiotype (FNHLId1) With Local GM-CSF in First Complete Remission
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Non-Hodgkins Lymphoma
Keywords: follicular
lymphoma
Non-Hodgkins
idiotype
vaccine
indolent follicular Non-Hodgkins Lymphoma
tumor-derived
B-cell
cancer
Lead sponsor: Biovest International
Sponsor class: INDUSTRY
First posted: 2004-09-17
Enrollment: 629
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: To demonstrate prolongation of the period of Disease Free Survival (significant prolongation of the period of complete remission) in idiotype vaccine treated patients
timeFrame: until date of relapse
Secondary outcomes:
measure: To determine the ability of the idiotype vaccine to produce a molecular complete remission
timeFrame: once subject achieves molecular CR
measure: To determine the impact of molecular disease free survival
timeFrame: until relapse
measure: To assess the ability of the idiotype vaccine to generate an immunologic response against the NHL tumor
timeFrame: varies
measure: To compare the overall survival of subjects randomized to receive either treatment
timeFrame: minimum 5 years from last subject randomized
measure: To confirm the safety of 5 monthly injections of the vaccine with GM-CSF
timeFrame: 4 days
Other outcomes:
Locations:
Study officials:
affiliation: Biovest International
name: Carlos F Santos, PhD
role: STUDY_DIRECTOR
affiliation: University of Pennsylvania
name: Stephen J Schuster, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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. doi: 10.1038/13928.
citation: 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.
citation: Dar MM, Kwak LW. Vaccination strategies for lymphomas. Curr Oncol Rep. 2003 Sep;5(5):380-6. doi: 10.1007/s11912-003-0022-x.
citation: 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.