This is a prospective, randomized, sequential, international, multicentric, 2-arm, non-comparative, open-label, 2-stage clinical study to determine disease response rates to Velcade™ therapy in subjects who have relapsed or refractory follicular B-cell lymphoma. Qualitative comparisons of the 2 treatment arms based on safety, efficacy and dosing convenience will be made in order to recommend a dose schedule for further clinical study.
This is a prospective, randomized, sequential, international, multicentric, 2-arm, non-comparative, open-label, 2-stage clinical study to determine disease response rates therapy of Velcade™ in subjects who have relapsed or refractory follicular B-cell lymphoma (FLL). Qualitative comparisons of the 2 treatment arms based on safety, efficacy and dosing convenience will be made in order to recommend a dose schedule for further clinical study. It is anticipated that approximatively 120 subjects will be enrolled to achieve the required 110 evaluable subjects, 55 in each treatment arm. Patients who receive any amount of Velcade™ are evaluable. Subjects not evaluable for response will be replaced. A central randomization will be used in this study. Subjects will be randomized and stratified with factors for prior therapies (1 or 2 versus \> 2) and time to progression (TPP) for the last given anti-neoplastic therapy (≤ 12 months versus \> 12 months). The eligible subjects will be randomized to either Treatment Arm A or Treatment Arm B in a 1:1 ratio: * Subjects randomized to Treatment Arm A will receive 1.5 mg/m² Velcade™ administered biweekly on Days 1, 4, 8, and 11 of a 21-day cycle. Patients will receive 8 cycles. The dose of Velcade™ received in schedule A will be 48 mg/m² over 24 weeks. * Subjects randomized to Treatment Arm B will receive 1.6 mg/m² Velcade™ administered weekly on Days 1, 8, 15, and 22 of a 35-day cycle. Patients will receive 6 cycles. The dose of Velcade™ received in schedule B will be 38.4 mg/m² over 30 weeks. Two additional cycles may be administered if the patient shows improvement to PR after 8 or 6 cycles for arm A or B, respectively. Study drug dose and schedule reduction for toxicity will be allowed during the study. A two stage interim analysis will be conducted in each treatment arm to determine whether either of the 2 treatments lacks sufficient efficacy. The final analysis will be conducted when all subjects have had the opportunity to complete the 30 day post-treatment evaluation visit. All data from all visits up until this point will be used in the final analysis, including data from any follow-up visits that have occurred. Patients will be recruited approximately over 2 years and followed until all data are available for final analysis. The total duration of the study is expected to be 5 years.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
87
Arm A: a 21-day cycle of 1.5 mg/m2 Velcade™ twice weekly for 2 weeks. Days 1, 4, 8, and 11 of a 21-day cycle
Arm B: a 35-day cycle of 1.6 mg/m2 Velcade™once weekly for 4 weeks. Days 1, 8, 15, and 22 of a 35-day cycle. Subjects in this treatment arm will receive a total of 6 cycles of treatment, approximately 30 weeks.
Groupe d'Etude des Lymphomes de l'adulte
Mont-Godinne, Belgium
Service d'Hématologie - Centre Hospitalier Lyon-Sud
Pierre-Bénite, France
Centre Henri Becquerel
Rouen, France
Institut Gustave Roussy
Villejuif, France
To determine the response rate to Velcade™ as a single agent
Time frame: End of treatment
To determine the overall complete response (CR) rate (CR + complete response unconfirmed [CRu])
Time frame: End of treatment
To determine time to progression (TTP)
Time frame: End of study
To determine overall survival
Time frame: End of study
To determine duration of response
Time frame: End of study
To determine the time to best response
Time frame: End of study
To evaluate the safety and tolerability of Velcade™
Time frame: End of study
To evaluate the effects of Velcade™ given biweekly at 1.5 mg/m2 versus 1.6 mg/m2 weekly
Time frame: End of study
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