Bortezomib Plus CHOP Every 2 Weeks for Advanced Stage DLBCL

Phase 1

Completed

• Conditions: Lymphoma, Large-Cell, Diffuse; Lymphoma, B-Cell
• Interventions: Drug: Bortezomib; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Vincristine; Drug: Prednisolone; Drug: Lenograstim

• Registration Number: NCT00379574
• Lead Sponsor: Asan Medical Center

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.

Study Timeline

• Study Start: 2006-09
• Study First Submitted: 2006-09-21
• Study First Submitted QC: 2006-09-21
• Study First Posted: 2006-09-22
• Primary Completion: 2011-01
• Study Completion: 2011-01
• Results First Submitted: 2011-02-04
• Results First Submitted QC: 2013-02-12
• Status Verified: 2013-03
• Last Update Submitted: 2013-03-13
• Results First Posted: 2013-03-14
• Last Update Posted: 2013-03-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 49

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Bortezomib + CHOP every 2 weeks	Vincristine	Bortezomib + CHOP(Cycloophosphamide, vincristine, doxorubicin,and predinisolone) every 2 weeks
Bortezomib + CHOP every 2 weeks	Prednisolone	Bortezomib + CHOP(Cycloophosphamide, vincristine, doxorubicin,and predinisolone) every 2 weeks
Bortezomib + CHOP every 2 weeks	Cyclophosphamide	Bortezomib + CHOP(Cycloophosphamide, vincristine, doxorubicin,and predinisolone) every 2 weeks
Bortezomib + CHOP every 2 weeks	Bortezomib	Bortezomib + CHOP(Cycloophosphamide, vincristine, doxorubicin,and predinisolone) every 2 weeks
Bortezomib + CHOP every 2 weeks	Doxorubicin	Bortezomib + CHOP(Cycloophosphamide, vincristine, doxorubicin,and predinisolone) every 2 weeks
Bortezomib + CHOP every 2 weeks	Lenograstim	Bortezomib + CHOP(Cycloophosphamide, vincristine, doxorubicin,and predinisolone) every 2 weeks

Primary Outcome Measures

Name	Time	Method
Number of Patients Who Achieved Complete Response	14 weeks	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.

Secondary Outcome Measures

Name	Time	Method
Number of Patients Who Experienced Adverse Events	6 months

Trial Locations

Locations (2)

Asan Medical Center, University of Ulsan College of Medicine; 🇰🇷 Seoul, Korea, Republic of

Asan Medical Cener; 🇰🇷 Seoul, Korea, Republic of