Phase 2 Study of VELCADE With Fludarabine in Comparison to Rituximab With Fludarabine in Follicular Lymphoma Patients Previously Treated With Rituximab

Study Overview
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Brief Summary
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This is a randomized, open-label, active-control, multicenter Phase 2 study of VELCADE+fludarabine in comparison with rituximab+fludarabine in subjects with relapsed advanced follicular lymphoma. Eligible subjects will be randomized in a 1:1 ratio between the 2 treatment arms (55 subjects per arm).

Official Title
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A Randomized, Open-Label, Multicenter Phase 2 Study of VELCADE With Fludarabine in Comparison to Rituximab With Fludarabine in Follicular Lymphoma Patients Previously Treated With Rituximab

Conditions
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Follicular Lymphoma

Intervention / Treatment
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* Drug: fludarabine
* Drug: rituximab
* Drug: VELCADE


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subjects 18 years or older Histologically proven diagnosis of follicular non-Hodgkin's lymphoma grades 1or 2 according to the World Health Organization classification Subjects must have received at least 12 doses (375mg/m2 or appropriately adjusted dose) of rituximab for the treatment of this lymphoma as single agent rituximab or in rituximab-containing regimens as documented in the subject's medical record Documented relapse or progression following last antineoplastic treatment At least 1 measurable tumor mass (≥1.5 cm x ≥1.0 cm) Exclusion Criteria: Subjects with histological or clinical transformation to an aggressive lymphoma prior treatment with VELCADE or fludarabine. antineoplastic (including unconjugated therapeutic antibodies), experimental, or radiation therapy within 3 weeks before randomization nitrosoureas within 6 weeks before randomization radioimmunoconjugates or toxin immunoconjugates within 10 weeks before randomization major surgery within 3 weeks before randomization chronic use of corticosteroids, such as dexamethasone

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VELCADE and fludarabine (Group A)<br>VELCADE 1.6 mg/m2 intravenously (IV) on Days 1, 8, 15, and 22 and fludarabine 40mg/m2/day orally on Days 1 to 5 of every 35-day cycle | Drug: fludarabine<br>* fludarabine 40mg/m2/day orally on Days 1 to 5 of every 35-day cycle<br>Drug: VELCADE<br>* 1.6 mg/m2 intravenously (IV) on Days 1, 8, 15, and 22 of every 35-day cycle<br>|
| Active Comparator: fludarabine and rituximab (Group B)<br>fludarabine 40mg/m2/day orally on Days 1 to 5 and rituximab 375mg/m2 on Day 1 of every 35-day cycle | Drug: fludarabine<br>* fludarabine 40mg/m2/day orally on Days 1 to 5 of every 35-day cycle<br>Drug: rituximab<br>* rituximab 375mg/m2 on Day 1 of every 35-day cycle<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Response Rate | The proportion of response-evaluable subjects who achieved a confirmed complete response (CR) or complete response unconfirmed (CRu). Disease response and progression were evaluated according to modified International Workshop Response Criteria (IWRC) criteria by radiographic imaging and other procedures as necessary. | Up to 8 cycles (1 cycle is 35 days: 280 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate | The proportion of subjects who achieve CR, CRu, or partial response (PR) relative to the response evaluable population. Disease response and progression were evaluated according to the modified IWRC criteria by radiographic imaging and other procedures as necessary. | Up to 8 cycles (1 cycle is 35 days: 280 days) |