A Phase II Study of VELCADE (Bortezomib) in Combination With Bendamustine and Rituximab in Subjects With Relapsed or Refractory Follicular Lymphoma

Study Overview
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Brief Summary
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This is a phase 2, single-arm, open label, multicenter study evaluating the efficacy and safety of the combination of VELCADE, bendamustine, and rituximab in subjects with relapsed or refractory follicular lymphoma, who have received 4 or more doses of rituximab. Subjects may be sensitive or refractory to prior therapies, including rituximab.

Official Title
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A Phase II Study of VELCADE (Bortezomib) in Combination With Bendamustine and Rituximab in Subjects With Relapsed or Refractory Follicular Lymphoma

Conditions
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Follicular Lymphoma

Intervention / Treatment
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* Drug: VELCADE
* Drug: Bendamustine
* Drug: Rituximab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subject 18 years of age or older Pathological diagnosis of follicular lymphoma (any grade) Documented relapse or progression following prior antineoplastic therapy Have received 4 or more prior doses of rituximab At least 1 measurable tumor mass (>1.5 cm in the long axis and >1.0 cm in the short axis that has not been previously irradiated, or has grown since previous irradiation No clinically significant central nervous system lymphoma Karnofsky performance status (KPS) ≥50 (equivalent to Eastern Cooperative Group Oncology Group [ECOG] status ≤2 Exclusion Criteria: Diagnosed or treated for a malignancy other than non-Hodgkin's lymphoma (NHL) within 2 years of first dose, or who were previously diagnosed with a malignancy other than NHL and have any radiographic or biochemical marker evidence of malignancy. Subjects with prostate cancer who were treated with definitive radiotherapy and have a serum prostate-specific antigen (PSA) <1 ng/mL are not excluded. Subjects are also not excluded if they have had basal cell or squamous cell carcinoma of the skin that was completely resected, or any in situ malignancy that was adequately treated. Prior treatment with VELCADE® or bendamustine Antineoplastic (including unconjugated therapeutic antibodies and toxin immunoconjugates), experimental, or radiation therapy within 3 weeks before Day 1 of Cycle 1 Nitrosoureas within 6 weeks before Day 1 of Cycle 1 Radioimmunoconjugates within 10 weeks before Day 1 of Cycle 1 Autologous stem cell transplant within 3 months before Day 1 of Cycle 1, or prior allogeneic stem cell transplant at any time Major surgery within 2 weeks before Day 1 of Cycle 1 Platelet transfusion within 7 days of Day 1 of Cycle 1 (applies to subjects enrolled in the dose escalation phase only. This does not apply to subjects enrolled in phase 2 of the study). Ongoing therapy with corticosteroids. Prednisone ≤15 mg per day or its equivalent is allowed.

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>This is a phase 2, single-arm, open label, multicenter study evaluating the efficacy and safety of the combination of VELCADE, bendamustine, and rituximab in subjects with relapsed or refractory follicular lymphoma, who have received 4 or more doses of rituximab. Subjects may be sensitive or refractory to prior therapies, including rituximab. | Drug: VELCADE<br>* VELCADE administered as a 3- to 5-second intravenous (IV) bolus prior to Bendamustine and Rituximab on Days 1,8,15 and 22 of each cycle.<br>Drug: Bendamustine<br>* Bendamustine administered IV over 30-60 minutes after VELCADE on Days 1 and 2 of each cycle<br>Drug: Rituximab<br>* Rituximab administered by IV infusion after VELCADE and Bendamustine on Days 1, 8, 15 and 22 of Cycle 1, and on Day 1 of Cycles 2, 3, 4 and 5<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Complete Response | Response is assessed by investigator according to International Working Group (IWG) criteria. Complete response requires disappearance of all evidence of disease. | 12 weeks after the last subject completes their end of treatment visit. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Overall Response (Complete and Partial Response) | Response is assessed by investigator according to International Working Group (IWG) criteria. Complete response requires disappearance of all evidence of disease. Partial response requires regression of measurable disease and no new sites. | 12 weeks after the last subject completes their end of treatment visit |