Bortezomib Plus CHOP Every 2 Weeks for Advanced Stage DLBCL

Lymphoma, B-Cell Clinical Trial

Official title:

A Phase I/II Study of Bortezomib Plus CHOP Every 2 Weeks in Patients With Advanced Stage Diffuse Large B-cell Lymphomas

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00379574
• Other study ID #: AMC 2006-276
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: September 21, 2006
• Last updated: March 13, 2013
• Start date: September 2006
• Est. completion date: January 2011

Study information

• Verified date: March 2013
• Source: Asan Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: Korea: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 49
• Est. completion date: January 2011
• Est. primary completion date: January 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 15 Years to 70 Years

Eligibility

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

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

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

Intervention

Drug:
• 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.
• Cyclophosphamide
cyclophosphamide 750mg/m2 day 1, every 2 weeks
• Doxorubicin
doxorubicin 50 mg/m2 day 1, every 2 weeks
• Vincristine
vincristine 1.4 mg/m2 (max. 2 mg) day 1, every 2 weeks
• Prednisolone
prednisolone 100 mg days 1-5, every 2 weeks
• Lenograstim
Lenograstim 5 microgram/kg subcutaneously days 4-13 every 2 weeks

Locations

Country	Name	City	State
Korea, Republic of	Asan Medical Cener	Seoul
Korea, Republic of	Asan Medical Center, University of Ulsan College of Medicine	Seoul

Sponsors (2)

Lead Sponsor	Collaborator
Asan Medical Center	Janssen Korea, Ltd., Korea

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	14 weeks	No
Secondary	Number of Patients Who Experienced Adverse Events		6 months	Yes