Bortezomib Plus CHOP Every 2 Weeks for Advanced Stage DLBCL

Asan Medical Center49 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

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

Interventions

BortezomibDRUG

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.

CyclophosphamideDRUG

cyclophosphamide 750mg/m2 day 1, every 2 weeks

DoxorubicinDRUG

doxorubicin 50 mg/m2 day 1, every 2 weeks

Eligibility

Sex: ALLMin age: 15 YearsMax age: 70 Years

Medical Language ↔ Plain English

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

Locations (2)

Asan Medical Center, University of Ulsan College of Medicine

Seoul, South Korea

Asan Medical Cener

Seoul, South Korea

Outcomes

Primary Outcomes

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.

Time frame: 14 weeks

Secondary Outcomes

Number of Patients Who Experienced Adverse Events

Time frame: 6 months

Data from ClinicalTrials.gov

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