Optimized Donor Selection, Nonmyeloablative BMT for B-cell Lymphomas With Post-transplantation Cy and Rituximab

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.

This phase II for relapsed or refractory B-cell malignancies builds on the platform of nonmyeloablative, related-donor, HLA (human leukocyte antigen)-matched or HLA-haploidentical BMT with post-transplantation high-dose cyclosphosphamide administered for prophylaxis of graft-versus-host disease and graft rejection. Rituximab is added to the transplant regimen with the goal of augmenting anti-tumor activity. In patients with B-cell lymphomas, specific polymorphisms in the immunoglobulin Fc receptor have been associated with greater sensitivity to rituximab or rituximab-based therapies, translating in some series into higher response rates and improved progression-free survival. This raises the possibility of selecting donors who carry this permissive polymorphism. This trial identifies and selects donors who have the favorable polymorphism at FcgammaR3A-158, thereby potentially conferring greater sensitivity to rituximab in the host after BMT.

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