Bortezomib Plus CHOP Every 2 Weeks for Advanced Stage DLBCL

NCT ID: NCT00379574

Last Updated: 2013-03-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 49 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-09-30
• Study Completion Date: 2011-01-31

Brief Summary

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

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.

Conditions

Lymphoma, Large-Cell, Diffuse; Lymphoma, B-Cell

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Bortezomib + CHOP every 2 weeks

Bortezomib + CHOP(Cycloophosphamide, vincristine, doxorubicin,and predinisolone) every 2 weeks

Group Type: EXPERIMENTAL

Bortezomib

Intervention Type: DRUG

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.

Cyclophosphamide

Intervention Type: DRUG

cyclophosphamide 750mg/m2 day 1, every 2 weeks

Doxorubicin

Intervention Type: DRUG

doxorubicin 50 mg/m2 day 1, every 2 weeks

Vincristine

Intervention Type: DRUG

vincristine 1.4 mg/m2 (max. 2 mg) day 1, every 2 weeks

Prednisolone

Intervention Type: DRUG

prednisolone 100 mg days 1-5, every 2 weeks

Lenograstim

Intervention Type: DRUG

Lenograstim 5 microgram/kg subcutaneously days 4-13 every 2 weeks

Interventions

Bortezomib

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.

Intervention Type: DRUG

Cyclophosphamide

cyclophosphamide 750mg/m2 day 1, every 2 weeks

Intervention Type: DRUG

Doxorubicin

doxorubicin 50 mg/m2 day 1, every 2 weeks

Intervention Type: DRUG

Vincristine

vincristine 1.4 mg/m2 (max. 2 mg) day 1, every 2 weeks

Intervention Type: DRUG

Prednisolone

prednisolone 100 mg days 1-5, every 2 weeks

Intervention Type: DRUG

Lenograstim

Lenograstim 5 microgram/kg subcutaneously days 4-13 every 2 weeks

Intervention Type: DRUG

Other Intervention Names

velcade; cytoxan; adriamycin; Oncovin; Pd; Neutrogin; G-CSF

Eligibility Criteria

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

• Minimum Eligible Age: 15 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen Korea, Ltd., Korea

INDUSTRY

Sponsor Role: collaborator

Asan Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Cheolwon Suh

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Cheolwon Suh, M.D.,Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Asan Medical Center

Locations

Asan Medical Center, University of Ulsan College of Medicine

Seoul, , South Korea

Asan Medical Cener

Seoul, , South Korea

Countries

South Korea

Other Identifiers

AMC 2006-276

Identifier Type: -

Identifier Source: org_study_id