Phase I/II Trial of VELCADE + CHOP-Rituximab in Untreated DLCBL or Mantle Cell NHL

Study Overview
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Brief Summary
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Primary Objective: To determine the toxicity profile and maximum tolerated dose (MTD) of VELCADE when administered in combination with CHOP + Rituximab to patients with previously untreated diffuse large B cell or mantle cell non-Hodgkin's lymphoma (NHL) Secondary Objectives: To assess the response rate (overall and complete), event-free survival and overall survival with VELCADE and CHOP-R in patients with previously untreated diffuse large B cell or mantle cell lymphoma (phase II component) Treatment: Standard CHOP chemotherapy administered every 21 days (full dose) for six cycles Rituximab administered (375 mg/m2) day 1 of each cycle (with usual premedications) VELCADE is administered prior to rituximab and CHOP on day 1 of each cycle. The dose of VELCADE will be determined by the following dose escalation schedule: Level Dose/Schedule (-2) 0.7 mg/m2 on day 1 of each cycle (-1) 0.7 mg/m2 on days 1 and 8 (0) 0.7 mg/m2 on days 1 and 4 (+1) 1.0 mg/m2 on days 1 and 4 (+2) 1.3 mg/m2 on days 1 and 4

Detailed Description
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Standard CHOP chemotherapy administered every 21 days (full dose) for six cycles Rituximab administered (375 mg/m2) day 1 of each cycle (with usual premedications) VELCADE is administered prior to rituximab and CHOP on day 1 of each cycle. The dose of VELCADE will be determined by the following dose escalation schedule: Once completed six cycles of therapy ( 18 weeks), patients will be evaluated every 3 months for the first year post treatment, then every 6 months until disease progression or death for years 2 through 5 post treatment. Patients who have disease progression will be contacted every 6 months until death to assess for survival status.

Official Title
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Phase I/II Trial of VELCADE+ CHOP-Rituximab in Patients With Previously Untreated Diffuse Large B Cell or Mantle Cell Non-Hodgkin's Lymphoma

Conditions
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Non-Hodgkin's Lymphoma

Intervention / Treatment
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* Drug: Bortezomib, CHOP, Rituximab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed diagnosis of diffuse large B cell or mantle cell Non-Hodgkin's Lymphoma with characteristic immunophenotypic profiles. For mantle cell: CD5(+), CD19(+) or CD20(+), cyclin D1(+), CD23(-) and CD10(-). Patient has not received any prior anti-cancer therapy for lymphoma Tumor tissue confirmed to express the CD20 antigen Available frozen tumor tissue(rebiopsy if needed) Patient has measurable disease as defined by a tumor mass > 1.5 cm Patient has Stage II, III, or IV disease Age > 18 years Absolute granulocyte count > 1000 cells/mm3 Platelet count > 50,000 cells/mm3 Creatinine < 2.0 x ULN Total bilirubin < 2.0 x ULN Exclusion Criteria: Known central nervous system (CNS) involvement by lymphoma Known HIV disease Patient is pregnant or nursing Patient has had major surgery within the last 3 weeks Patient is receiving other investigational drugs Known peripheral neuropathy > Grade 2

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
Interventional Model Description: Standard CHOP chemotherapy administered every 21 days (full dose) for six cycles Rituximab administered (375 mg/m2) day 1 of each cycle (with usual premedications) VELCADE is administered prior to rituximab and CHOP on day 1 of each cycle. The dose of VELCADE will be determined by the dose escalation schedule.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br>Standard CHOP chemotherapy administered every 21 days (full dose) for six cycles Rituximab administered (375 mg/m2) day 1 of each cycle (with usual premedications) VELCADE (Bortezomib) is administered prior to rituximab and CHOP on day 1 of each cycle. The dose of VELCADE will be determined by a dose escalation schedule. | Drug: Bortezomib, CHOP, Rituximab<br>* Standard CHOP chemotherapy administered every 21 days (full dose) for six cycles Rituximab administered (375 mg/m2) day 1 of each cycle (with usual premedications) VELCADE (Bortezomib) is administered prior to rituximab and CHOP on day 1 of each cycle. The dose of VELCADE will be determined by the following dose escalation schedule: Level Dose/Schedule (-2) 0.7 mg/m2 on day 1 of each cycle (-1) 0.7 mg/m2 on days 1 and 8 (0) 0.7 mg/m2 on days 1 and 4 (+1) 1.0 mg/m2 on days 1 and 4 (+2) 1.3 mg/m2 on days 1 and 4<br>* Other names: VELCADE;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR | Overall Response Rate | 6 cycles (18 weeks) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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diffuse large B cell, mantle cell lymphoma