Phase 2 Study of VELCADE (Bortezomib) in Patients With Relapsed Follicular Lymphoma

Study Overview
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Brief Summary
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This is a phase 2, two-arm, non-randomized, open-label, multicenter study evaluating the safety and efficacy of 2 VELCADE-containing regimens. Patients will be treated with either a combination of VELCADE, rituximab, cyclophosphamide, doxorubicin, and prednisone (VELCADE-R-CAP) or a combination of VELCADE, rituximab, cyclophosphamide, and prednisone (VELCADE-R-CP) based on investigator preference. Following completion of the treatment period, patients will receive maintenance therapy with rituximab up to a maximum of 2 years.

Official Title
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A Two-Arm, Non-Randomized, Multicenter, Phase 2 Study of VELCADE (Bortezomib) in Combination With Rituximab, Cyclophosphamide, and Prednisone With or Without Doxorubicin Followed by Rituximab Maintenance in Patients With Relapsed Follicular Lymphoma.

Conditions
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Relapsed Follicular Lymphoma

Intervention / Treatment
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* Drug: rituximab
* Drug: cyclophosphamide
* Drug: doxorubicin
* Drug: VELCADE
* Drug: prednisone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patient 18 years of age or older Pathological diagnosis of follicular lymphoma (any grade) or marginal zone lymphoma. Patients with transformed follicular lymphoma are eligible, provided there has previously been pathologic documentation of follicular lymphoma. Documented relapse or progression following prior antineoplastic therapy At least 1 measurable tumor mass that is greater than 1.5 cm in the long axis and greater than 1.0 cm in the short axis that has not been previously irradiated, or has grown since previous irradiation No clinically significant evidence of active 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. Patients with prostate cancer who were treated with definitive radiotherapy who have a serum prostate-specific antigen <1 ng/mL are not excluded. Patients are 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. Received any of the following treatments or procedures outside of the specified timeframes: Prior treatment with VELCADE Prior treatment with a cumulative dose of doxorubicin of more than 100 mg/m2, if assigned to Arm A (VELCADE-R-CAP) 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

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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VELCADE R-CAP<br>VELCADE will be administered as a 3- to 5-second intravenous bolus injection, rituximab 375 mg/m2 Intravenous on Day 1, cyclophosphamide 750 mg/m2 intravenous on Day 1, doxorubicin 50 mg/m2 intravenous on Day 1, VELCADE 1.6 mg/m2 intravenous on Days 1 and 8, prednisone 100 mg orally on Days 1 to 5 of a 21-day (3-week) cycle for 6 cycles. | Drug: rituximab<br> <br> Drug: cyclophosphamide<br> <br> Drug: doxorubicin<br> <br> Drug: VELCADE<br> <br> Drug: prednisone<br> <br> |
| Experimental: VELCADE R-CP<br>VELCADE will be administered as a 3- to 5-second intravenous bolus injection, rituximab 375 mg/m2 intravenous on Day 1, cyclophosphamide 1000 mg/m2 intravenous on Day 1, VELCADE 1.6 mg/m2 intravenous on Days 1 and 8, prednisone 100 mg orally on Days 1 to 5 of a 21-day (3-week) cycle for 6 cycles. | Drug: rituximab<br> <br> Drug: cyclophosphamide<br> <br> Drug: VELCADE<br> <br> Drug: prednisone<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With Complete Response (CR) | Disappearance of all evidence of disease assessed by computed tomography (CT) and PET (position-emission tomography) according to the revised International Working Group (IWG) Criteria. | 30 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Overall Response (OR) | OR = Complete Response (CR) + Partial Response (PR)according to the revised International Working Group (IWG) Criteria. CR is the disappearance of all evidence of disease assessed by CT and PET. PR is the regression of measurable disease and no new sites assessed by CT and PET. | 30 weeks | 
| Percentage of Participants With Progression-free Survival (PFS) at 1 Year | PFS was defined as the time from the first dose to the date of progressive disease (PD)/relapse or death, whichever comes first. For a participant who had not progressed/relapsed or died, PFS was censored at the last response assessment that was stable disease (failure to attain complete response/partial response or PD or better). | Assessed at at the end of Cycle 2, at end of treatment visit, and every 12± 1 weeks for the first year (4 visits) until PD | 
| Duration of Response | Time (in months) from the first documentation of a response (CR or partial response [PR]) to the date of first documentation of progressive disease or relapse from complete response. CR is defined as disappearance of all evidence of disease assessed by CT or PET; PR is defined as regression of measurable disease and no new sites assessed by CT or PET according to the revised International Working Group (IWG) Criteria. | 2 years | 
| Number of Patients Who Experienced at Least One Serious Adverse Event |  | From completion of informed consent through 30 days after the last dose of study drug |