A Phase II Study of Allo-HCT for B-Cell NHL Using Zevalin, Fludarabine and Melphalan
Condition: Graft Versus Host Disease; Leukemia; Lymphoma
MeSH terms: Lymphoma; Leukemia; Graft vs Host Disease
Study type: Interventional
Phase: Phase 2

Summary: 
      RATIONALE: Giving monoclonal antibody therapy, radioimmunotherapy, and chemotherapy before a
      donor stem cell transplant helps stop the growth of cancer cells and helps stop the patient's
      immune system from rejecting the donor's stem cells. When the stem cells from a related donor
      that do not exactly match the patient's blood, are infused into the patient, they may help
      the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets.
      Sometimes the transplanted cells from a donor can also make an immune response against the
      body's normal cells. Giving tacrolimus and sirolimus before and after transplant may stop
      this from happening.

      PURPOSE: This phase II trial is studying the side effects and how well giving indium In 111
      ibritumomab tiuxetan and yttrium y 90 ibritumomab tiuxetan together with rituximab,
      fludarabine, melphalan, and donor stem cell transplant works in treating patients with B-cell
      non-Hodgkin lymphoma.
    

Detailed description: 
      PRIMARY OBJECTIVES: I. To evaluate the safety and efficacy of a preparative regimen of
      Yttrium-90 (90^Y)- labeled anti-cluster of differentiation (CD)20 monoclonal antibody (MAb)
      (yttrium Y 90 ibritumomab tiuxetan) in combination with fludarabine (fludarabine phosphate)
      and melphalan followed by allogeneic hematopoietic stem cell transplant (APBSCT) for
      treatment of patients with B-cell low-grade non-Hodgkin lymphoma (LG NHL), intermediate-grade
      non-Hodgkin lymphoma (IG NHL) and mantle cell lymphoma (MCL). II. To evaluate the short- and
      long-term complications of this new preparative regimen, including rates of engraftment,
      acute and chronic graft-versus-host-disease (GVHD) and infectious complications. III. To
      estimate the disease response rate, disease relapse (progression) rate, and non-relapse
      mortality rate. IV. To perform exploratory studies that seek to measure/characterize the
      expression of costimulatory molecules and impact of these molecules on the natural killer
      (NK) and T cells of a subset of lymphoma patients pre- post- allogeneic stem cell transplant
      (ASCT) and the stem cell product from a portion of sibling donors.

      OUTLINE: REDUCED-INTENSITY CONDITIONING: Patients receive rituximab intravenously (IV)
      followed by indium In-111 ibritumomab tiuxetan IV over 10 minutes on day -21 and rituximab IV
      followed by yttrium Y 90 ibritumomab tiuxetan IV over 10 minutes on day -14. Patients also
      receive fludarabine phosphate IV on days -9 to -5 and melphalan IV on day -4.

      STEM CELL TRANSPLANTATION: Patients undergo APBSCT on day 0.

      GVHD PROPHYLAXIS: Patients receive tacrolimus IV or orally (PO) and sirolimus PO beginning on
      day -3 and continuing for up to 6 months with taper.

      After completion of study treatment, patients are followed up every 3 months for 1 year and
      then every 6 months for up to 5 years.
    

Intervention name(s): rituximab; fludarabine phosphate; melphalan; sirolimus; tacrolimus; allogeneic hematopoietic stem cell transplantation; indium In 111 ibritumomab tiuxetan; yttrium Y 90 ibritumomab tiuxetan; laboratory biomarker analysis
Intervention type(s): Biological; Drug; Drug; Drug; Drug; Procedure; Radiation; Radiation; Other
Intervention description(s): Given IV; Given IV; Given IV; Given PO; Given PO or IV; Undergo APBSCT; Given IV; Given IV; Correlative Studies
Other intervention name(s): IDEC-C2B8; IDEC-C2B8 monoclonal antibody; Mabthera; MOAB IDEC-C2B8; Rituxan; 2-F-ara-AMP; Beneflur; Fludara; Alkeran; CB-3025; L-PAM; L-phenylalanine mustard; L-Sarcolysin; AY 22989; Rapamune; rapamycin; SLM; FK 506; Prograf; IDEC-In2B8; 90Y ibritumomab tiuxetan; IDEC Y2B8; Y90 Zevalin; Y90-labeled ibritumomab tiuxetan
Intervention MeSH terms: Sirolimus; Rituximab; Fludarabine; Fludarabine phosphate; Melphalan; Tacrolimus; Antibodies, Monoclonal
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: graft versus host disease; contiguous stage II grade 1 follicular lymphoma; contiguous stage II grade 2 follicular lymphoma; contiguous stage II grade 3 follicular lymphoma; noncontiguous stage II grade 1 follicular lymphoma; noncontiguous stage II grade 2 follicular lymphoma; noncontiguous stage II grade 3 follicular lymphoma; recurrent grade 1 follicular lymphoma; recurrent grade 2 follicular lymphoma; recurrent grade 3 follicular lymphoma; stage I grade 1 follicular lymphoma; stage I grade 2 follicular lymphoma; stage I grade 3 follicular lymphoma; stage III grade 1 follicular lymphoma; stage III grade 2 follicular lymphoma; stage III grade 3 follicular lymphoma; stage IV grade 1 follicular lymphoma; stage IV grade 2 follicular lymphoma; stage IV grade 3 follicular lymphoma; contiguous stage II adult diffuse large cell lymphoma; noncontiguous stage II adult diffuse large cell lymphoma; recurrent adult diffuse large cell lymphoma; stage I adult diffuse large cell lymphoma; stage III adult diffuse large cell lymphoma; stage IV adult diffuse large cell lymphoma; Waldenstrom macroglobulinemia; contiguous stage II marginal zone lymphoma; extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue; nodal marginal zone B-cell lymphoma; noncontiguous stage II marginal zone lymphoma; recurrent marginal zone lymphoma; stage I marginal zone lymphoma; stage III marginal zone lymphoma; stage IV marginal zone lymphoma; B-cell chronic lymphocytic leukemia; refractory chronic lymphocytic leukemia; stage I chronic lymphocytic leukemia; stage II chronic lymphocytic leukemia; stage III chronic lymphocytic leukemia; stage IV chronic lymphocytic leukemia; contiguous stage II mantle cell lymphoma; noncontiguous stage II mantle cell lymphoma; recurrent mantle cell lymphoma; stage I mantle cell lymphoma; stage III mantle cell lymphoma; stage IV mantle cell lymphoma; contiguous stage II adult diffuse mixed cell lymphoma; noncontiguous stage II adult diffuse mixed cell lymphoma; recurrent adult diffuse mixed cell lymphoma; stage I adult diffuse mixed cell lymphoma; stage III adult diffuse mixed cell lymphoma; stage IV adult diffuse mixed cell lymphoma; contiguous stage II small lymphocytic lymphoma; noncontiguous stage II small lymphocytic lymphoma; recurrent small lymphocytic lymphoma; stage I small lymphocytic lymphoma; stage III small lymphocytic lymphoma; stage IV small lymphocytic lymphoma