Bortezomib Plus CHOP Every 2 Weeks for Advanced Stage DLBCL

Asan Medical Center

Status and phase

Completed

Phase 2

Phase 1

Conditions

Lymphoma, B-Cell

Lymphoma, Large-Cell, Diffuse

Treatments

Drug: Doxorubicin

Drug: Lenograstim

Drug: Cyclophosphamide

Drug: Bortezomib

Drug: Vincristine

Drug: Prednisolone

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT00379574

AMC 2006-276

Details and patient eligibility

About

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.

Full 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.

Enrollment

49 patients

Sex

All

Ages

15 to 70 years old

Volunteers

No Healthy Volunteers

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