Chemotherapy, Radiation Therapy, Rituximab, and Umbilical Cord Blood Transplant in Treating Patients With B-Cell Non-Hodgkin's Lymphoma
Condition: Leukemia; Lymphoma
MeSH terms: Lymphoma; Leukemia
Intervention: filgrastim; rituximab; cyclophosphamide; cyclosporine; fludarabine phosphate; mycophenolate mofetil; allogeneic hematopoietic stem cell transplantation; umbilical cord blood transplantation; total-body irradiation
Intervention MeSH terms: Cyclosporine; Mycophenolic Acid; Cyclophosphamide; Rituximab; Fludarabine; Fludarabine phosphate; Cyclosporins
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 17.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: recurrent mantle cell lymphoma; stage III mantle cell lymphoma; stage IV mantle 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; extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue; nodal marginal zone B-cell lymphoma; recurrent marginal zone lymphoma; recurrent adult diffuse small cleaved cell lymphoma; splenic marginal zone lymphoma; recurrent grade 1 follicular lymphoma; recurrent grade 2 follicular lymphoma; recurrent 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; 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; noncontiguous stage II marginal zone lymphoma; stage III marginal zone lymphoma; stage IV marginal zone lymphoma; noncontiguous stage II adult diffuse small cleaved cell lymphoma; stage III adult diffuse small cleaved cell lymphoma; stage IV adult diffuse small cleaved cell lymphoma; noncontiguous stage II adult diffuse large cell lymphoma; noncontiguous stage II mantle cell lymphoma

Summary:

      RATIONALE: Giving low doses of chemotherapy, such as cyclophosphamide and fludarabine,
      total-body irradiation, and rituximab before a donor umbilical cord blood stem cell
      transplant helps stop the growth of cancer cells. It also stops the patient's immune system
      from rejecting the donor's stem 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 cyclosporine and mycophenolate mofetil after the transplant may
      stop this from happening.

      PURPOSE: This phase II trial is studying how well giving chemotherapy and radiation therapy
      together with rituximab and an umbilical cord blood transplant works in treating patients
      with B-cell non-Hodgkin's lymphoma.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Diagnosis of 1 of the following:

               -  CD20+* aggressive B-cell non-Hodgkin's lymphoma (NHL), including 1 of the
                  following:

                    -  Diffuse large cell (DLC) NHL 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 (IPI) score and in second complete remission (CR) or
                            partial remission (PR) after prior autologous stem cell transplantation

                         -  Failed prior autologous stem cell transplantation and in at least PR
                            after salvage chemotherapy

                    -  Large cell transformation of indolent NHL/chronic lymphocytic leukemia (CLL)
                       meeting the following criteria:

                         -  CR/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, as defined by p53 positivity and in first CR/PR after
                            initial therapy

                         -  Relapsed disease after initial therapy and in second or third CR/PR
                            after salvage chemotherapy

               -  CD20+* indolent NHL or CLL meeting the following criteria:

                    -  Must be in second or subsequent progression (pre-allograft cytoreduction
                       necessary but CR/PR not required)

                    -  Indolent NHL includes, but is not limited to, any of the following:

                         -  Follicular NHL

                         -  Small cell NHL

                         -  Marginal zone NHL NOTE: *CD20 positivity must be demonstrated within
                            the past 12 months

          -  Relapsed disease must be biopsy proven

          -  Prior pre-allograft cytoreduction may have included 1 of the following:

               -  Single autologous stem cell transplantation with high-dose chemotherapy
                  conditioning, if appropriate, and no conditioning prior to transplantation

               -  Two or more courses of intensive combination chemotherapy (e.g., rituximab,
                  irinotecan hydrochloride, cetuximab, epirubicin hydrochloride [RICE]) as
                  appropriate according to diagnosis and prior therapy

                    -  Heavily pre-treated CLL patients in whom further combination chemotherapy is
                       not appropriate may receive single-agent intermediate-dose cyclophosphamide
                       for 2-3 courses

          -  No mantle cell or DLC NHL with progressive disease at allograft work-up

          -  No suitable matched related or unrelated donor available

          -  Two umbilical cord blood (UCB) units available meeting the following criteria:

               -  Units and recipient must be ≥ 4/6 HLA-A and -B antigen and DRB1 allele matched

               -  Each unit must have ≥ 1.5 x 10^7 total nucleated cells/recipient body weight

        PATIENT CHARACTERISTICS:

          -  Karnofsky performance score 70-100%

          -  Creatinine clearance ≥ 50 mL/min

          -  Bilirubin < 2.5 mg/dL

          -  AST and ALT ≤ 3 times upper limit of normal (unless due to benign congenital
             hyperbilirubinemia)

          -  Spirometry and corrected DLCO ≥ 50% normal

          -  LVEF ≥ 40%

          -  Albumin ≥ 2.5 g/dL

          -  No active and uncontrolled infection at time of transplantation, including active
             infection with Aspergillus or other mold

          -  No HIV positivity

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception

        PRIOR CONCURRENT THERAPY:

          -  See Disease Characteristics

          -  No more than 120 days since prior autologous stem cell transplantation

          -  No more than 60 days since prior chemotherapy

          -  No prior allogeneic transplantation