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

Study Overview
=================
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.

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

Conditions
-----------------
Non-Hodgkins Lymphoma

Intervention / Treatment
-----------------
* Biological: FNHLId1
* Biological: KLH + GM-CSF


Participation Criteria
=================
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ID-KLH + GM-CSF<br> | Biological: FNHLId1<br>* 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<br>|
| Active Comparator: KLH + GM-CSF<br> | Biological: KLH + GM-CSF<br>* 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<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To demonstrate prolongation of the period of Disease Free Survival (significant prolongation of the period of complete remission) in idiotype vaccine treated patients |  | until date of relapse | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the ability of the idiotype vaccine to produce a molecular complete remission |  | once subject achieves molecular CR | 
| To determine the impact of molecular disease free survival |  | until relapse | 
| To assess the ability of the idiotype vaccine to generate an immunologic response against the NHL tumor |  | varies | 
| To compare the overall survival of subjects randomized to receive either treatment |  | minimum 5 years from last subject randomized | 
| To confirm the safety of 5 monthly injections of the vaccine with GM-CSF |  | 4 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
follicular, lymphoma, Non-Hodgkins, idiotype, vaccine, indolent follicular Non-Hodgkins Lymphoma, tumor-derived, B-cell, cancer