Bortezomib Plus CHOP Every 2 Weeks for Advanced Stage DLBCL

Study Overview
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Brief Summary
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Diffuse large B-cell lymphoma is a most prevalent non-Hodgkin's lymphoma. Recently the clinical results have been improved with new drugs and new modalities such as cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) every 2 weeks. Bortezomib is well known to be effective for multiple myeloma and has been being tried for other malignancies including lymphoma. The investigators will incorporate Bortezomib to CHOP every 2 weeks to further improve the clinical efficacy in diffuse large B-cell lymphoma.

Detailed Description
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Intended number of patients: 63 patients in total Phase I: 9 patients for 3 levels Phase II: 50 patients plus 3 patient from Phase I at MTD level Plus 4 patients: considering 5% follow-up loss rate Study design and methodology: For phase I, 9 patients; 3 levels of bortezomib (1.0, 1.3 and 1.6 mg/m2), 3 patients at each dose level. If escalation of bortezomib beyond 1.0 mg/m2 is not possible, the trial will be stopped. For phase II, 53 patients (3 from phase I at MTD level); Reject when complete response rate equal or less than 12/19 or 37/53 by Simon two-stage optimal phase II design. Treatments: Bortezomib: For phase I, 3 dose levels (1.0, 1.3 or 1.6 mg/m2), days 1 and 4, every 2 weeks. For phase II, suggested dose of Bortezomib through phase I, days 1 and 4, every 2 weeks. CHOP2: cyclophosphamide 750mg/ m2 day 1, vincristine 1.4 mg/ m2 (max. 2 mg) day 1, doxorubicin 50 mg/ m2 day 1, prednisolone 100 mg days 1-5, every 2 weeks. G-CSF: Lenograstim 5 microgram/kg subcutaneously days 4-13 every 2 weeks.

Official Title
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A Phase I/II Study of Bortezomib Plus CHOP Every 2 Weeks in Patients With Advanced Stage Diffuse Large B-cell Lymphomas

Conditions
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Lymphoma, Large-Cell, Diffuse, Lymphoma, B-Cell

Intervention / Treatment
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* Drug: Bortezomib
* Drug: Cyclophosphamide
* Drug: Doxorubicin
* Drug: Vincristine
* Drug: Prednisolone
* Drug: Lenograstim


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed DLBCL Age 70 years or less Previously untreated Performance status: ECOG 0-2 Advanced stage: stage III, IV, or non-contiguous stage II Measurable disease: 1 cm or more by spiral CT Normal liver function Exclusion Criteria: Platelet count less than 75,000/microL within 14 days before enrollment. Absolute neutrophil count of less than 1,500/microlL within 14 days before enrollment. Cr more than 2.0 mg/dL and/or calculated or measured creatinine clearance less than 50 mL/min within 14 days before enrollment. Peripheral neuropathy of Grade 2 or worse within 14 days before enrollment. Hypersensitivity to bortezomib, boron or mannitol. Female subject is pregnant or breast-feeding. Other investigational drugs with 14 days before enrollment Serious medical or psychiatric illness likely to interfere with participation in this clinical study. Uncontrolled or severe cardiovascular disease, including MI within 6 months of enrolment, New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, clinically significant pericardial disease, or cardiac amyloidosis

Ages Eligible for Study
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Minimum Age: 15 Years
Maximum Age: 70 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: Bortezomib + CHOP every 2 weeks<br>Bortezomib + CHOP(Cycloophosphamide, vincristine, doxorubicin,and predinisolone) every 2 weeks | Drug: Bortezomib<br>* Bortezomib: For phase I, 3 dose levels (1.0, 1.3 or 1.6 mg/m2), days 1 and 4, every 2 weeks. For phase II, suggested dose of Bortezomib through phase I, days 1 and 4, every 2 weeks.<br>* Other names: velcade;Drug: Cyclophosphamide<br>* cyclophosphamide 750mg/m2 day 1, every 2 weeks<br>* Other names: cytoxan;Drug: Doxorubicin<br>* doxorubicin 50 mg/m2 day 1, every 2 weeks<br>* Other names: adriamycin;Drug: Vincristine<br>* vincristine 1.4 mg/m2 (max. 2 mg) day 1, every 2 weeks<br>* Other names: Oncovin;Drug: Prednisolone<br>* prednisolone 100 mg days 1-5, every 2 weeks<br>* Other names: Pd;Drug: Lenograstim<br>* Lenograstim 5 microgram/kg subcutaneously days 4-13 every 2 weeks<br>* Other names: G-CSF;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients Who Achieved Complete Response | All patients,9 patients of phase I study and 40 patietns in phase II stuay, were assessed with International Working Group response criteria assessed by CT; Complete Response (CR), Disappearance of all detectable clinical and radiographic evidence of disease and diappearance of all disease-related symptoms. | 14 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients Who Experienced Adverse Events |  | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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diffuse large B-cell lymphoma, Bortezomib, CHOP, Lenograstim