Bortezomib and Rituximab in Treating Patients With Non-Hodgkin's Lymphoma

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Jonsson Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00093769
First received: October 6, 2004
Last updated: October 3, 2012
Last verified: October 2012
  Purpose

RATIONALE: Bortezomib may stop the growth of cancer cells by blocking the enzymes necessary for their growth. Monoclonal antibodies such as rituximab can locate cancer cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Giving bortezomib together with rituximab may kill more cancer cells.

PURPOSE: This randomized phase II trial is studying how well giving bortezomib together with rituximab works in treating patients with relapsed or refractory non-Hodgkin's lymphoma.


Condition Intervention Phase
Lymphoma
Drug: bortezomib + rituximab
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of VELCADE With Rituximab in Subjects With Relapsed or Refractory Indolent B-Cell Lymphoma

Resource links provided by NLM:


Further study details as provided by Jonsson Comprehensive Cancer Center:

Primary Outcome Measures:
  • Response rate (complete response [CR], CR-unconfirmed [CRu], and partial response [PR]) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Response rate (CR, CRu, and PR) at the first disease response evaluation [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Overall CR rate (CR and CRu) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Safety and tolerability [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]

Enrollment: 15
Study Start Date: August 2004
Primary Completion Date: August 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: bortezomib + rituximab

Arm I: Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Patients also receive rituximab IV on days 1, 8, and 15 of course 1 only and on day 1 of course 2 only. Treatment with repeats every 21 days for up to 5 courses in the absence of disease progression or unacceptable toxicity.

Arm II: Patients receive bortezomib IV over 3-5 seconds on days 1, 8, 15 and 22. Patients also receive rituximab IV on days 1, 8, 15, and 22 of course 1 only. Treatment repeats every 35 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.

Patients in either arm may crossover to the other arm if treatment is found to be ineffective.

Drug: bortezomib + rituximab

Arm I: Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Patients also receive rituximab IV on days 1, 8, and 15 of course 1 only and on day 1 of course 2 only. Treatment with repeats every 21 days for up to 5 courses in the absence of disease progression or unacceptable toxicity.

  • Arm II: Patients receive bortezomib IV over 3-5 seconds on days 1, 8, 15 and 22. Patients also receive rituximab IV on days 1, 8, 15, and 22 of course 1 only. Treatment repeats every 35 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.

Patients in either arm may crossover to the other arm if treatment is found to be ineffective.


Detailed Description:

OBJECTIVES:

Primary

  • Determine the response rate (complete response [CR], CR-unconfirmed [CRu], and partial response [PR]) in patients with relapsed or refractory indolent B-cell non-Hodgkin's lymphoma treated with bortezomib and rituximab.

Secondary

  • Determine the response rate (CR, CRu, and PR) at the first disease response evaluation in patients treated with this regimen.
  • Determine the overall CR rate (CR and CRu) in patients treated with this regimen.
  • Determine the time to progression in patients treated with this regimen.
  • Determine the duration of response in patients treated with this regimen.
  • Determine the time to best response in patients treated with this regimen.
  • Determine the safety and tolerability of this regimen in these patients.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to participating center, Karnofsky performance status (< 70% vs ≥ 70%), lactic dehydrogenase level (normal vs > upper limit of normal), age (18 to 60 years vs > 60 years), and lymphoma subtype (follicular vs marginal zone). Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Patients also receive rituximab IV on days 1, 8, and 15 of course 1 only and on day 1 of course 2 only. Treatment with repeats every 21 days for up to 5 courses in the absence of disease progression or unacceptable toxicity.
  • Arm II: Patients receive bortezomib IV over 3-5 seconds on days 1, 8, 15 and 22. Patients also receive rituximab IV on days 1, 8, 15, and 22 of course 1 only. Treatment repeats every 35 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.

Patients in either arm may crossover to the other arm if treatment is found to be ineffective.

Patients are followed at 30 days and then every 12 weeks thereafter.

PROJECTED ACCRUAL: A total of 24-66 patients (12-33 per treatment arm) will be accrued for this study within 1 year.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Diagnosis of indolent B-cell non-Hodgkin's lymphoma of 1 of the following subtypes:

    • Follicular (grade 1, 2, or 3)
    • Marginal zone (extranodal, nodal, or splenic)
  • CD20-positive disease
  • Relapsed or progressive disease after prior anti-neoplastic therapy, as indicated by 1 of the following:

    • New lesions
    • Objective evidence of progression of existing lesions
  • Complete response ≥ 6 months in duration after prior rituximab therapy* NOTE: *For patients who were previously treated with a regimen that included rituximab
  • At least 1 measurable lymph node mass > 1.5 cm in 2 perpendicular dimensions that has not been irradiated OR that has progressed since prior radiotherapy
  • No active CNS lymphoma

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Performance status

  • Karnofsky 50-100% OR
  • ECOG 0-2

Life expectancy

  • Not specified

Hematopoietic

  • Absolute neutrophil count ≥ 1,000/mm^3
  • Platelet count ≥ 50,000/mm^3

Hepatic

  • AST and ALT ≤ 3 times upper limit of normal (ULN)
  • Bilirubin ≤ 2 times ULN

Renal

  • Creatinine ≤ 2 mg/dL OR
  • Creatinine clearance ≥ 30 mL/min

Immunologic

  • No known anaphylaxis or immunoglobulin E-mediated hypersensitivity to murine proteins or to any component of rituximab, including polysorbate 80 and sodium citrate dihydrate
  • No active systemic infection requiring treatment
  • No history of allergic reaction attributable to compounds containing boron or mannitol

Other

  • No peripheral neuropathy or neuropathic pain ≥ grade 2
  • No other malignancy within the past 5 years except completely resected basal cell or squamous cell skin cancer or an in situ malignancy

    • Previously diagnosed prostate cancer allowed provided the following criteria are met:

      • T1-2a, N0, M0 disease AND Gleason score ≤ 7 AND prostate specific antigen (PSA) ≤ 10 ng/mL before initial therapy
      • Treated with definitive curative therapy (i.e., prostatectomy or radiotherapy) within the past 2 years
      • No clinical evidence of prostate cancer AND undetectable PSA (for prostatectomy patients) or PSA < 1 ng/mL (for patients who did not undergo prostatectomy)
  • No serious medical or psychiatric illness that would preclude study participation
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • See Disease Characteristics
  • More than 10 weeks since prior radioimmunoconjugates or toxin immunoconjugates (e.g., ibritumomab tiuxetan or iodine I 131 tositumomab)
  • More than 4 weeks since prior rituximab, alemtuzumab, or other unconjugated therapeutic antibody
  • No concurrent prophylactic bone marrow growth factors (e.g., filgrastim [G-CSF], sargramostim [GM-CSF], or epoetin alfa) during course 1 of study therapy

Chemotherapy

  • More than 6 weeks since prior nitrosoureas
  • No concurrent cisplatin

Endocrine therapy

  • No concurrent corticosteroids (e.g., dexamethasone) except prednisone ≤ 15 mg/day or equivalent for adrenal insufficiency

Radiotherapy

  • See Disease Characteristics
  • See Biologic therapy
  • More than 3 weeks since prior radiotherapy
  • No concurrent radiotherapy

Surgery

  • More than 2 weeks since prior major surgery

Other

  • Recovered from all prior therapy
  • No prior bortezomib
  • More than 3 weeks since prior antineoplastic therapy
  • More than 3 weeks since prior experimental therapy
  • No other concurrent antineoplastic therapy
  • No other concurrent investigational agents

    • Concurrent participation in a non-treatment study allowed provided it does not interfere with participation in this study
  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: NCT00093769

Locations
United States, California
Jonsson Comprehensive Cancer Center at UCLA
Los Angeles, California, United States, 90095
Sponsors and Collaborators
Jonsson Comprehensive Cancer Center
Investigators
Principal Investigator: Sven De Vos, MD Jonsson Comprehensive Cancer Center
  More Information

Additional Information:
Publications:
Responsible Party: Jonsson Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00093769     History of Changes
Other Study ID Numbers: CDR0000390235, UCLA-0401054-01, MILLENNIUM-M34103-061
Study First Received: October 6, 2004
Last Updated: October 3, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Jonsson Comprehensive Cancer Center:
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
nodal marginal zone B-cell lymphoma
recurrent marginal zone lymphoma
splenic marginal zone lymphoma

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Rituximab
Bortezomib
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 22, 2014