Study of Bortezomib Combined With ACVBP in Peripheral T-cell Lymphoma

Study Overview
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Brief Summary
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The purpose of this study is to determine the efficacy and the safety profile and toxicity of a combination of Velcade™ (bortezomib) with a standard chemotherapy regimen (ACVBP [doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone]) in the treatment of previously untreated patients with peripheral T-cell lymphoma (PTCL).

Detailed Description
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This is a multicentric, open-label, non-randomized, non-competitive clinical study, evaluating the efficacy and safety of V-ACVBP chemotherapy in previously untreated patients aged from 18 to 65 years with peripheral T-lymphoma. It is anticipated that 60 subjects will be enrolled over two years (from June 2005 to May 2007). The duration of the treatment period is approximately 28 weeks and patients are followed until death. The total duration of the study is expected to be 5 years (from June 2005 to May 2010).

Official Title
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A Phase II Study Evaluating the Efficacy and Safety of Bortezomib (Velcade™) Combined With ACVBP Regimen in Patients With Previously Untreated Peripheral T-cell Lymphoma

Conditions
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Peripheral T-cell Lymphoma

Intervention / Treatment
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* Drug: Velcade
* Drug: Doxorubicin
* Drug: Prednisone
* Drug: Cyclophosphamide
* Drug: Vindesine
* Drug: Bleomycin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Previously untreated non-cutaneous peripheral T-cell lymphoma, including human T-cell lymphotropic virus type 1 (HTLV-1) related T-cell lymphoma, and natural killer (NK)-cell lymphoma. Ages 18 to 65 years. Life expectancy > 3 months. Written informed consent. Exclusion Criteria: B-cell lymphoma or other subtype of T-cell lymphoma including anaplastic large cell lymphoma AKL(+), lymphoblastic lymphoma and primary cutaneous T-cell lymphoma. Any previous therapy for lymphoma except for short-term corticosteroids before inclusion. Inability to tolerate the ACVBP regimen according to investigator's judgement. Positive serology for HIV. Poor renal function (creatinin > 150 µmol/l within 14 days before enrollment), poor liver function (total bilirubin > 30 µmol/l, transaminases > 2.5 upper normal limit [UNL] within 14 days before enrollment), unless these abnormalities are related to the lymphoma. Poor bone marrow reserve as defined by neutrophils < 1.5 G/l or platelets < 100 G/l within 14 days before enrollment, unless these abnormalities are related to the lymphoma. Patient with >= grade 2 peripheral neuropathy non-related to lymphoma. Any central nervous system (CNS) disease. CNS or meningeal involvement by the lymphoma. Any serious active disease or comorbidity according to the investigator's decision. Any history of cancer during the last 5 years with the exception of non-melanoma skin tumours or stage 0 (in situ) cervical carcinoma. Known hypersensitivity to bortezomib, boron or mannitol. Contraindication to any cytotoxic drug contained in chemotherapy regimen. Pregnant or lactating women or women of childbearing potential not willing to use an adequate method of birth control (i.e. hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of study. Men not agreeing to take adequate contraceptive precautions during the study. Treatment with investigational drug within 30 days before planned first cycle of chemotherapy and during the study. Adult patient under tutelage.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Experimental<br>Velcade, Doxorubicine, Cyclophosphamide, Vindesine, Bleomycin, Prednisone | Drug: Velcade<br>* 1.5 mg/m², D1, D5, 4 cycles<br>Drug: Doxorubicin<br>* 75 mg/m², D1, 4 cycles<br>Drug: Prednisone<br>* 60 mg/m², D1-D5, 4 cycles<br>Drug: Cyclophosphamide<br>* 1200 mg/m², D1, 4 cycles<br>Drug: Vindesine<br>* 2 mg/m², D1, D5, 4 cycles<br>Drug: Bleomycin<br>* 10 mg, D1, D5, 4 cycles<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Event-free survival (EFS) | percentage of patients alive with no event, events being defined as disease progression, institution of a new treatment for the lymphoma, relapse after complete response (CR), or death from any cause | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete response rate unconfirmed (CR+CR uncertain) | percentage of patients with complete response | 2 years | 
| Partial response (PR) rate | percentage of patients with partial response | 2 years | 
| Progression free survival (PFS) | Duration of survival without progression | 2 years | 
| Duration of response in complete responders (CR + CRu) |  | 2 years | 
| Overall survival (OS) | Percentage of patients alive | 2 years | 
| Number of SAE |  | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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peripheral T-cell lymphomas, bortezomib, ACVBP regimen