Optimized Donor Selection, Nonmyeloablative BMT for B-cell Lymphomas With Post-transplantation Cy and Rituximab
Condition: Lymphoma; B-cell Lymphoma; Non Hodgkin Lymphoma; Chronic Lymphocytic Leukemia
MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Leukemia, Lymphocytic, Chronic, B-Cell
Intervention: Fludarabine; Cyclophosphamide; Total body irradiation; Tacrolimus; Mycophenolate Mofetil; Rituximab; Allogeneic Bone Marrow Transplant (BMT)
Intervention description: Days -6 through -2: 30 mg/m^2 IV daily; Days -6 and -5: 14.5 mg/kg IV daily; Days 3 and 4: 50 mg/kg IV daily; Day -1: 200 centigray (cGy) in a single fraction; Start on Day 5 through Day 180; Days 5 through 35: 15 mg/kg PO three times daily (max 3 g/day); Day 30 and every week after for 8 total doses: 375 mg/m^2 IV; Day 0: Donor bone marrow infusion
Intervention MeSH terms: Mycophenolic Acid; Cyclophosphamide; Rituximab; Fludarabine; Tacrolimus
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 135.0
Sex: All
Minimum age: 1 Year
Maximum age: 75 Years
Healthy volunteers: No
Keywords: lymphoma; non hodgkin lymphoma; allogeneic; bone marrow transplantation; nonmyeloablative; cyclophosphamide; rituximab

Summary:

      This phase II trial is studying how well giving fludarabine and cyclophosphamide together
      with total-body irradiation and rituximab works in treating patients with B-cell lymphoma or
      chronic lymphocytic leukemia who are undergoing an allogeneic (donor) bone marrow transplant.
      The type of bone marrow transplant is a less intensive or "mini" transplant using a relative
      as the bone marrow donor. The donated bone marrow stem cells may replace the patient's immune
      system cells and help destroy any remaining cancer (graft-versus-tumor effect). Patients
      undergoing this type of transplant often have more than one relative who could be a donor.
      The trial is also studying a new way of choosing amongst possible donors which might improve
      how the rituximab works.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Poor-risk CD20+, B-cell lymphoma, as follows:

               -  Low grade B-cell lymphoma that has failed at least two prior therapies (excluding
                  single agent rituximab), or undergone histologic conversion (if histologic
                  conversion, PR or CR is required):

                    1. Follicular grade 1 or 2 lymphoma

                    2. Follicular lymphoma not otherwise specified

                    3. Marginal zone (or MALT) lymphoma

                    4. Lymphoplasmacytic lymphoma / Waldenstrom's macroglobulinemia

                    5. Hairy cell leukemia

                    6. Small lymphocytic lymphoma / chronic lymphocytic leukemia (SLL/CLL)

                    7. Low grade B-cell lymphoma, unspecified

                    8. Nodular lymphocyte-predominant Hodgkin lymphoma

          -  Poor-risk small lymphocytic lymphoma or chronic lymphocytic leukemia, defined by a 17p
             deletion, 11q deletion, or histologic conversion (if histologic conversion, PR or CR
             is required)

          -  Aggressive B-cell non-Hodgkin's lymphoma that has failed at least one prior regimen of
             multiagent chemotherapy, is in PR (partial remission) or CR (complete remission), and
             patient is either ineligible for autologous hematopoietic BMT or autologous BMT is not
             recommended:

               1. Follicular grade 3 lymphoma

               2. Histoconversion of low-grade B-cell lymphoma (including SLL/CLL) to aggressive
                  B-cell non-Hodgkin's lymphoma

               3. Mantle cell lymphoma

               4. Diffuse large B-cell lymphoma (excluding primary CNS [central nervous system]
                  lymphoma)

               5. "Gray zone" or composite lymphomas with combined features of primary mediastinal
                  large B-cell and Hodgkin's lymphoma

               6. Burkitt's lymphoma/leukemia

               7. Atypical Burkitt's lymphoma/leukemia (high grade B-cell lymphoma, unclassified,
                  including that with features intermediate between Burkitt's and diffuse large
                  B-cell lymphoma)

          -  Must have a related donor who is at least HLA haploidentical

          -  Any previous BMT must have occurred at least 3 months prior

          -  Left ventricular ejection fraction at least 35%

          -  Bilirubin no more than 3.0 mg/dL (unless due to Gilbert's syndrome), and ALT (alanine
             aminotransferase) and AST (aspartate aminotransferase) no more than 5 x upper limit of
             normal

          -  FEV1 (forced expiratory volume in one second) and FVC (forced vital capacity) at least
             40% of predicted

          -  Absence of uncontrolled infection

        Exclusion Criteria:

          -  More than 20% involvement of bone marrow by chronic lymphocytic leukemia

          -  Active central nervous system lymphoma

          -  ECOG (Eastern Cooperative Oncology Group) performance status greater than 1 (2,3, and
             4)

          -  HIV positive

          -  Pregnant or breastfeeding