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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

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ClinicalTrials.gov Identifier: NCT00334438
Recruitment Status : Completed
First Posted : June 7, 2006
Last Update Posted : December 23, 2016
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
UNC Lineberger Comprehensive Cancer Center

Brief Summary:

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 or disease Intervention/treatment Phase
Lymphoma Biological: rituximab Drug: bortezomib Radiation: yttrium Y 90 ibritumomab tiuxetan Radiation: Indium 111 ibritumomab tiuxetan Phase 1

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 12 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Study Start Date : July 2006
Actual Primary Completion Date : October 2008
Actual Study Completion Date : October 2011


Arm Intervention/treatment
Zevalin + Velcade Single Arm Study
Zevalin (Ibritumomab Tiuxetan) and Velcade (Bortezomib)
Biological: rituximab
250mg/m2, IV, Days 1 and 8
Other Name: Rituxan

Drug: bortezomib
dose escalation 1.0, 1.3, or 1.5, IVP; Days 4, 8, 11, 15
Other Name: Velcade

Radiation: yttrium Y 90 ibritumomab tiuxetan
Dose dependant upon platelet count (0.4mCi/kg) not to exceed 32mCi; Day 8

Radiation: Indium 111 ibritumomab tiuxetan
5cmCi; IV day 1




Primary Outcome Measures :
  1. Maximum tolerated dose of bortezomib [ Time Frame: 2 years ]
  2. Dose-limiting toxicity [ Time Frame: 8 weeks ]

Secondary Outcome Measures :
  1. Response rate [ Time Frame: 5 years ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 120 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00334438


Locations
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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
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Thomas C. Shea, MD UNC Lineberger Comprehensive Cancer Center

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Responsible Party: UNC Lineberger Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00334438     History of Changes
Other Study ID Numbers: LCCC 0525
CDR0000550130 ( Other Identifier: PDQ number )
First Posted: June 7, 2006    Key Record Dates
Last Update Posted: December 23, 2016
Last Verified: December 2016

Keywords provided by UNC Lineberger Comprehensive Cancer Center:
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:
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Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Rituximab
Bortezomib
Antibodies, Monoclonal
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents