Bortezomib Plus CHOP Every 2 Weeks for Advanced Stage DLBCL

This study has been completed.
Sponsor:
Collaborator:
Janssen Korea, Ltd., Korea
Information provided by (Responsible Party):
Cheolwon Suh, Asan Medical Center
ClinicalTrials.gov Identifier:
NCT00379574
First received: September 21, 2006
Last updated: March 13, 2013
Last verified: March 2013
  Purpose

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.


Condition Intervention Phase
Lymphoma, Large-Cell, Diffuse
Lymphoma, B-Cell
Drug: Bortezomib
Drug: Cyclophosphamide
Drug: Doxorubicin
Drug: Vincristine
Drug: Prednisolone
Drug: Lenograstim
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Study of Bortezomib Plus CHOP Every 2 Weeks in Patients With Advanced Stage Diffuse Large B-cell Lymphomas

Resource links provided by NLM:


Further study details as provided by Asan Medical Center:

Primary Outcome Measures:
  • Number of Patients Who Achieved Complete Response [ Time Frame: 14 weeks ] [ Designated as safety issue: No ]
    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:
  • Number of Patients Who Experienced Adverse Events [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]

Enrollment: 49
Study Start Date: September 2006
Study Completion Date: January 2011
Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Bortezomib + CHOP every 2 weeks
Bortezomib + CHOP(Cycloophosphamide, vincristine, doxorubicin,and predinisolone) every 2 weeks
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.

Other Name: velcade
Drug: Cyclophosphamide
cyclophosphamide 750mg/m2 day 1, every 2 weeks
Other Name: cytoxan
Drug: Doxorubicin
doxorubicin 50 mg/m2 day 1, every 2 weeks
Other Name: adriamycin
Drug: Vincristine
vincristine 1.4 mg/m2 (max. 2 mg) day 1, every 2 weeks
Other Name: Oncovin
Drug: Prednisolone
prednisolone 100 mg days 1-5, every 2 weeks
Other Name: Pd
Drug: Lenograstim
Lenograstim 5 microgram/kg subcutaneously days 4-13 every 2 weeks
Other Names:
  • Neutrogin
  • G-CSF

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

Ages Eligible for Study:   15 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00379574

Locations
Korea, Republic of
Asan Medical Cener
Seoul, Korea, Republic of
Asan Medical Center, University of Ulsan College of Medicine
Seoul, Korea, Republic of, 138-736
Sponsors and Collaborators
Asan Medical Center
Janssen Korea, Ltd., Korea
Investigators
Principal Investigator: Cheolwon Suh, M.D.,Ph.D. Asan Medical Center
  More Information

No publications provided

Responsible Party: Cheolwon Suh, Professor, Asan Medical Center
ClinicalTrials.gov Identifier: NCT00379574     History of Changes
Other Study ID Numbers: AMC 2006-276
Study First Received: September 21, 2006
Results First Received: February 4, 2011
Last Updated: March 13, 2013
Health Authority: Korea: Food and Drug Administration

Keywords provided by Asan Medical Center:
diffuse large B-cell lymphoma
Bortezomib
CHOP
Lenograstim

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Large B-Cell, Diffuse
Lymphoma, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Cyclophosphamide
Liposomal doxorubicin
Bortezomib
Doxorubicin
Vincristine
Prednisolone
Methylprednisolone Hemisuccinate
Lenograstim
Methylprednisolone acetate
Prednisolone acetate
Methylprednisolone
Prednisolone hemisuccinate
Prednisolone phosphate
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating

ClinicalTrials.gov processed this record on September 18, 2014