Clinical trial NCT00379574: Bortezomib Plus CHOP Every 2 Weeks for Advanced Stage DLBCL
Official title: A Phase I/II Study of Bortezomib Plus CHOP Every 2 Weeks in Patients With Advanced Stage Diffuse Large B-cell Lymphomas
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Lymphoma, Large-Cell, Diffuse
Lymphoma, B-Cell
Keywords: diffuse large B-cell lymphoma
Bortezomib
CHOP
Lenograstim
Lead sponsor: Asan Medical Center
Sponsor class: OTHER
Collaborators: name: Janssen Korea, Ltd., Korea
First posted: 2006-09-22
Enrollment: 49
Sex: ALL
Minimum age (years): 15
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Number of Patients Who Achieved Complete Response
timeFrame: 14 weeks
Secondary outcomes:
measure: Number of Patients Who Experienced Adverse Events
timeFrame: 6 months
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center, University of Ulsan College of Medicine
city: Seoul
country: Korea, Republic of
facility: Asan Medical Cener
Study officials:
affiliation: Asan Medical Center
name: Cheolwon Suh, M.D.,Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: