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Bortezomib, Rituximab, and Yttrium Y 90 Ibritumomab Tiuxetan in Treating Patients With Relapsed or Refractory Low-Grade, Follicular, or Mantle Cell Non-Hodgkin's Lymphoma
This study is ongoing, but not recruiting participants.
First Received: June 6, 2006   Last Updated: February 6, 2009   History of Changes
Sponsor: UNC Lineberger Comprehensive Cancer Center
Collaborator: National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00334438
  Purpose

RATIONALE: Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as rituximab, and radiolabeled monoclonal antibodies, such as yttrium Y 90 ibritumomab tiuxetan, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them without harming normal cells. Giving bortezomib together with rituximab and yttrium Y 90 ibritumomab tiuxetan may kill more cancer cells.

PURPOSE: This phase I trial is studying the side effects and best dose of bortezomib when given together with rituximab and yttrium Y 90 ibritumomab tiuxetan in treating patients with relapsed or refractory low-grade, follicular, or mantle cell non-Hodgkin's lymphoma.


Condition Intervention Phase
Lymphoma
Biological: rituximab
Drug: bortezomib
Radiation: yttrium Y 90 ibritumomab tiuxetan
Phase I

Study Type: Interventional
Study Design: Treatment, Non-Randomized, Open Label
Official Title: A Phase I Study Evaluating Combined Zevalin (Ibritumomab Tiuxetan) and Valcade (Bortezomib) in Relapsed/Refractory Low-Grade or Follicular B-Cell and Mantle Cell Lymphoma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Maximum tolerated dose of bortezomib [ Designated as safety issue: Yes ]
  • Dose-limiting toxicity [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Response rate [ Designated as safety issue: No ]

Estimated Enrollment: 18
Study Start Date: July 2006
Detailed Description:

OBJECTIVES:

Primary

  • Determine the maximum tolerated dose (MTD) of bortezomib in combination with rituximab and yttrium Y 90 ibritumomab tiuxetan in patients with relapsed or refractory low-grade, follicular B-cell, or mantle cell non-Hodgkin's lymphoma.
  • Determine the dose-limiting toxicity of this regimen in these patients.

Secondary

  • Determine the response rate in patients treated with this regimen.

OUTLINE: This is a multicenter, open-label, nonrandomized, dose-escalation study of bortezomib.

Patients receive rituximab IV over 4 hours followed by indium In 111 ibritumomab tiuxetan IV over 10 minutes on day 1 to assess biodistribution. Patients without altered biodistribution receive rituximab IV over 4 hours followed by yttrium Y 90 ibritumomab tiuxetan IV over 10 minutes on day 8. Patients also receive bortezomib IV over 3-5 seconds on days 4, 8, 11, and 15.

Cohorts of 3-6 patients receive escalating doses of bortezomib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Additional patients may be treated at the MTD.

After completion of study treatment, patients are followed every 3 months for 18 months and then every 6 months thereafter.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Histologically confirmed low-grade, follicular B-cell, or mantle cell non-Hodgkin's lymphoma

    • Bone marrow biopsy required for pretreatment evaluation

      • Unilateral bone marrow biopsy allowed
      • Core biopsies allowed if they contain adequate tissue for primary diagnosis and immunophenotyping
  • Relapsed or refractory disease as defined by disease progression after initial complete response (CR) or failure to achieve CR
  • No bone marrow involvement ≥ 25% within the past 30 days
  • No pleural effusion or significant ascites
  • No active CNS involvement

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-2
  • Life expectancy ≥ 3 months
  • Platelet count ≥ 100,000/mm^3
  • Absolute neutrophil count ≥ 1,500/mm^3
  • AST ≤ 2.5 times upper limit of normal (ULN)
  • Total bilirubin ≤ 2.5 times ULN
  • Creatinine clearance ≥ 50 mL/min
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Hepatitis B surface antigen negative
  • No current infection with hepatitis B virus
  • No HIV positivity
  • No neuropathy or neuropathic pain ≥ grade 2
  • No history of allergic reaction to boron or mannitol
  • No active serious infection or medical or psychiatric illness that would preclude study therapy
  • No other malignancy within the past 5 years except for the following:

    • Basal cell or squamous cell carcinoma of the skin that has been completely resected
    • In situ malignancy that has been completely resected
    • T1-T2a, N0, M0 prostate cancer treated with a prostatectomy or radiotherapy within the past 2 years with an undetectable PSA level
  • No other condition, including any of the following:

    • Myocardial infarction within the past 6 months
    • New York Heart Association class III-IV heart failure
    • Uncontrolled angina
    • Severe uncontrolled ventricular arrhythmias
    • Electrocardiographic evidence of acute ischemia or active conduction system abnormalities

PRIOR CONCURRENT THERAPY:

  • Recovered from all prior therapy
  • More than 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C), radiotherapy, or surgical resection of malignancy

    • No limitations on the number of prior therapies
  • More than 4 weeks since prior major surgery
  • More than 14 days since prior filgrastim (G-CSF) or sargramostim (GM-CSF)
  • More than 14 days since prior and no other concurrent investigational agents

    • Concurrent participation in a nontreatment study allowed
  • No prior radioimmunotherapy
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00334438

Locations
United States, New Jersey
Hackensack University Medical Center Cancer Center
Hackensack, New Jersey, United States, 07601
United States, North Carolina
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
Chapel Hill, North Carolina, United States, 27599-7295
Sponsors and Collaborators
UNC Lineberger Comprehensive Cancer Center
Investigators
Principal Investigator: Thomas C. Shea, MD UNC Lineberger Comprehensive Cancer Center
  More Information

Additional Information:
No publications provided

Study ID Numbers: CDR0000550130, UNC-LCCC-0525
Study First Received: June 6, 2006
Last Updated: February 6, 2009
ClinicalTrials.gov Identifier: NCT00334438     History of Changes
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
recurrent mantle cell lymphoma
recurrent small lymphocytic lymphoma

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

ClinicalTrials.gov processed this record on November 11, 2009