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
Condition: Lymphoma
MeSH terms: Lymphoma
Study type: Interventional
Phase: Phase 1

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.
    

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.
    

Intervention name(s): rituximab; bortezomib; yttrium Y 90 ibritumomab tiuxetan; Indium 111 ibritumomab tiuxetan
Intervention type(s): Biological; Drug; Radiation; Radiation
Intervention description(s): 250mg/m2, IV, Days 1 and 8; dose escalation 1.0, 1.3, or 1.5, IVP; Days 4, 8, 11, 15; Dose dependant upon platelet count (0.4mCi/kg) not to exceed 32mCi; Day 8; 5cmCi; IV day 1
Other intervention name(s): Rituxan; Velcade
Intervention MeSH terms: Rituximab; Bortezomib; Antibodies, Monoclonal
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: recurrent grade 1 follicular lymphoma; recurrent grade 2 follicular lymphoma; recurrent grade 3 follicular lymphoma; recurrent mantle cell lymphoma; recurrent small lymphocytic lymphoma