Chemotherapy, Total-Body Irradiation, Rituximab, and Donor Stem Cell Transplant in Treating Patients With B-Cell Non-Hodgkin's Lymphoma or Chronic Lymphocytic Leukemia
Condition: Leukemia; Lymphoma
MeSH terms: Lymphoma; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell
Intervention: anti-thymocyte globulin; filgrastim; graft-versus-tumor induction therapy; rituximab; cyclophosphamide; cyclosporine; fludarabine phosphate; mycophenolate mofetil; nonmyeloablative allogeneic hematopoietic stem cell transplantation; total-body irradiation
Intervention MeSH terms: Cyclosporine; Mycophenolic Acid; Cyclophosphamide; Rituximab; Fludarabine; Fludarabine phosphate; Cyclosporins; Antilymphocyte Serum
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 61.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: noncontiguous stage II adult diffuse large cell lymphoma; recurrent adult diffuse large cell lymphoma; stage III adult diffuse large cell lymphoma; stage IV adult diffuse large cell lymphoma; B-cell chronic lymphocytic leukemia; refractory chronic lymphocytic leukemia; stage III chronic lymphocytic leukemia; stage IV chronic lymphocytic leukemia; noncontiguous stage II mantle cell lymphoma; recurrent mantle cell lymphoma; stage III mantle cell lymphoma; stage IV mantle cell lymphoma; noncontiguous stage II grade 1 follicular lymphoma; noncontiguous stage II grade 2 follicular lymphoma; recurrent grade 1 follicular lymphoma; recurrent grade 2 follicular lymphoma; stage III grade 1 follicular lymphoma; stage III grade 2 follicular lymphoma; stage IV grade 1 follicular lymphoma; stage IV grade 2 follicular lymphoma; noncontiguous stage II small lymphocytic lymphoma; recurrent small lymphocytic lymphoma; stage III small lymphocytic lymphoma; stage IV small lymphocytic lymphoma; noncontiguous stage II marginal zone lymphoma; recurrent marginal zone lymphoma; splenic marginal zone lymphoma; stage III marginal zone lymphoma; stage IV marginal zone lymphoma; noncontiguous stage II adult immunoblastic large cell lymphoma; stage III adult immunoblastic large cell lymphoma; stage IV adult immunoblastic large cell lymphoma; extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue; nodal marginal zone B-cell lymphoma; recurrent adult immunoblastic large cell lymphoma

Summary:

      RATIONALE: Giving low doses of chemotherapy and total-body irradiation before a donor stem
      cell transplant helps stop the growth of cancer cells. It also helps stop the patient's
      immune system from rejecting the donor's stem cells. Also, monoclonal antibodies, such as
      rituximab, can find cancer cells and either kill them or deliver cancer-killing substances to
      them without harming normal cells. The donated stem cells may replace the patient's immune
      cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the
      transplanted cells from a donor can also make an immune response against the body's normal
      cells. Giving rituximab before transplant and cyclosporine and mycophenolate mofetil after
      transplant may stop this from happening.

      PURPOSE: This phase II trial is studying the side effects and how well giving chemotherapy
      and radiation therapy together with rituximab and donor stem cell transplant works in
      treating patients with B-cell non-Hodgkin's lymphoma or chronic lymphocytic leukemia.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Diagnosis of 1 of the following:

               -  CD20-positive aggressive B-cell non-Hodgkin's lymphoma (NHL), including any of
                  the following subtypes:

                    -  Diffuse large cell lymphoma*, meeting 1 of the following criteria:

                         -  Relapsed disease after initial therapy, but failed to mobilize or had
                            bone marrow involvement and therefore is not suitable for an autologous
                            stem cell transplantation

                         -  High-intermediate- or high-risk second-line, age-adjusted International
                            Prognostic Index score and in second complete remission (CR) or partial
                            remission (PR) after autologous stem cell transplantation

                         -  Failed prior autologous stem cell transplantation and in PR or better
                            after salvage chemotherapy

                    -  Large cell transformation of indolent NHL or chronic lymphocytic leukemia
                       (CLL), meeting the following criteria:

                         -  In CR or PR of the large cell component of disease after salvage
                            chemotherapy or autologous stem cell transplantation

                    -  Mantle cell lymphoma*, meeting 1 of the following criteria:

                         -  High-risk disease (e.g., p53 positivity) and in first CR or PR after
                            initial therapy

                         -  Relapsed disease after initial therapy and in second or third CR or PR
                            after salvage chemotherapy NOTE: *No progressive disease at allograft
                            work-up

               -  CD20-positive indolent NHL (e.g., follicular lymphoma, small cell lymphoma, or
                  marginal zone NHL) OR CLL

                    -  Second or subsequent progression (pre-allograft cytoreduction necessary, but
                       CR or PR not required)

          -  Relapsed disease must be biopsy-proven

          -  Must have received pre-allograft salvage chemotherapy, including 1 of the following:

               -  Single autologous stem cell transplantation using high-dose chemotherapy
                  conditioning within the past 120 days

               -  At least 2 courses of intensive combination chemotherapy (e.g., RICE [rituximab,
                  ifosfamide, carboplatin, etoposide]), according to diagnosis, within the past 80
                  days

               -  CLL patients who have received CAMPATH do not have to receive pre-allograft
                  salvage chemotherapy

          -  HLA-compatible related or unrelated donor available

               -  HLA-matched ≥ 9/10 of the A, B, C, DRB1, and DQB1 loci, as tested by high
                  resolution typing

                    -  One allele mismatch allowed

        PATIENT CHARACTERISTICS:

          -  Karnofsky performance status 70-100%

          -  Creatinine < 1.2 mg/mL OR creatinine clearance ≥ 50 mL/min

          -  Bilirubin < 2.5 mg/dL

          -  AST and ALT ≤ 3 times upper limit of normal (unless benign congenital
             hyperbilirubinemia is present)

          -  Spirometry and corrected DLCO ≥ 50% of normal

          -  LVEF ≥ 40%

          -  Albumin ≥ 2.5 g/dL

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception

          -  No active uncontrolled infection, including active infection with Aspergillus or other
             mold

          -  No HIV infection

          -  No hepatitis B antibody or antigen positivity

        PRIOR CONCURRENT THERAPY:

          -  See Disease Characteristics

          -  No prior allogeneic transplantation