Bortezomib in Treating Patients With Diffuse Large B-Cell Lymphoma That Is Refractory To Chemotherapy

A Phase II Study Of PS-341 (VELCADE) In Chemotherapy-Refractory Diffuse Large B-Cell Lymphoma (DLBCL)

RATIONALE: Bortezomib may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth.

PURPOSE: Phase II trial to study the effectiveness of bortezomib in treating patients who have diffuse large B-cell lymphoma that is refractory to previous chemotherapy.

Study Overview

• Status: Completed
• Conditions: Lymphoma
• Intervention / Treatment: Drug: bortezomib

Detailed Description

OBJECTIVES:

• Determine the overall response rate in patients with chemotherapy-refractory diffuse large B-cell lymphoma treated with bortezomib.
• Determine the safety and tolerability of this drug in these patients.
• Determine the time to disease progression in patients treated with this drug.
• Determine the possible mechanism of resistance to this drug in these patients.

OUTLINE: This is an open-label, multicenter study.

Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed at 20 days and then every 3 months thereafter.

PROJECTED ACCRUAL: A total of 22-40 patients will be accrued for this study.

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • Jonsson Comprehensive Cancer Center at UCLA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Histologically confirmed diffuse large B-cell lymphoma, meeting criteria for 1 of the following:

  • Relapsed after prior high-dose chemotherapy with stem cell support
  • Relapsed after prior chemotherapy, including at least 1 prior standard non-Hodgkin's chemotherapy regimen, but not a candidate for high-dose chemotherapy with stem cell support

• Measurable disease

  • At least 1 bidimensionally measurable lesion at least 1.5 cm by CT scan
• No primary or secondary CNS lymphoma
• No HIV-related lymphoma
• No known brain metastases

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2 OR
• Karnofsky 60-100%

Life expectancy

• More than 3 months

Hematopoietic

• Hemoglobin at least 9 g/dL

• Absolute neutrophil count at least 1,000/mm^3

  • No colony-stimulating factors within 4 weeks before obtaining this result

• Platelet count at least 50,000/mm^3

  • No platelet transfusion within 4 weeks before obtaining this result

Hepatic

• Bilirubin no greater than 2 times upper limit of normal (ULN)
• AST and ALT no greater than 2.5 times ULN
• No active hepatitis B or C viral infection

Renal

• Creatinine no greater than 2 times ULN OR
• Creatinine clearance at least 60 mL/min

Cardiovascular

• No myocardial infarction within the past 6 months
• No evidence of acute ischemia or new conduction system abnormalities on EKG
• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Sodium greater than 130 mEq/L
• HIV negative
• No ongoing or active infection
• No other concurrent uncontrolled illness that would preclude study participation
• No psychiatric illness or social situation that would preclude study compliance
• No prior allergic reaction attributable to compounds of similar chemical or biological composition to bortezomib

PRIOR CONCURRENT THERAPY:

Biologic therapy

• See Disease Characteristics
• See Chemotherapy
• At least 4 weeks since prior immunotherapy

Chemotherapy

• See Disease Characteristics
• More than 4 weeks since prior chemotherapy
• More than 12 weeks since prior high-dose chemotherapy with hematopoietic stem cell support

Endocrine therapy

• Not specified

Radiotherapy

• More than 4 weeks since prior radiotherapy
• No concurrent radiotherapy

Surgery

• More than 4 weeks since prior major surgery unless fully recovered

Other

• Recovered from prior therapy
• No other concurrent investigational agents
• No other concurrent investigational or commercial agents or therapies to treat the malignancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Overall response rate (combined complete response and partial response)

Secondary Outcome Measures

Outcome Measure
Time to disease progression
Safety
Tolerability
Possible mechanism of resistance

Collaborators and Investigators

• Sponsor: Jonsson Comprehensive Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Sven De Vos, MD, Jonsson Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start: May 1, 2003
• Primary Completion (Actual): July 1, 2005

Study Registration Dates

• First Submitted: August 6, 2003
• First Submitted That Met QC Criteria: August 6, 2003
• First Posted (Estimate): August 7, 2003

Study Record Updates

• Last Update Posted (Estimate): January 8, 2013
• Last Update Submitted That Met QC Criteria: January 7, 2013
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Keywords: recurrent adult diffuse large cell lymphoma
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Lymphoma; Lymphoma, Large B-Cell, Diffuse; Antineoplastic Agents; Bortezomib
• Other Study ID Numbers: CDR0000316254; UCLA-0301090