Chemotherapy, Total-Body Irradiation, Rituximab, and Donor Stem Cell Transplant in Treating Patients With B-Cell Non-Hodgkin's Lymphoma or Chronic Lymphocytic Leukemia

Study Overview
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Brief Summary
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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.

Official Title
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A Non-Myeloablative Conditioning Regimen With Peri-Transplant Rituximab and the Transplantation of Hematopoietic Stem Cells From HLA-Compatible Related or Unrelated Donors in Patients With B Cell Lymphoid Malignancies

Conditions
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Leukemia, Lymphoma

Intervention / Treatment
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* Biological: anti-thymocyte globulin
* Biological: filgrastim
* Biological: graft-versus-tumor induction therapy
* Biological: rituximab
* Drug: cyclophosphamide
* Drug: cyclosporine
* Drug: fludarabine phosphate
* Drug: mycophenolate mofetil
* Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation
* Radiation: total-body irradiation


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: treatment<br>This is a phase 2 study of a treatment regimen consisting of a non-myeloablative (NMA) conditioning regimen incorporating low dose chemotherapy and low dose radiation as well as peri-transplant Rituximab and the transplantation of peripheral blood stem cells (PBSC) or bone marrow if PBSC collection not possible from an HLA compatible related or unrelated donor in patients with B cell lymphoid malignancies including diffuse large cell (DLC) and mantle cell non-Hodgkin's lymphoma (NHL), indolent B cell NHL, or chronic lymphocytic leukemia (CLL). | Biological: anti-thymocyte globulin<br> <br> Biological: filgrastim<br> <br> Biological: graft-versus-tumor induction therapy<br> <br> Biological: rituximab<br> <br> Drug: cyclophosphamide<br> <br> Drug: cyclosporine<br> <br> Drug: fludarabine phosphate<br> <br> Drug: mycophenolate mofetil<br> <br> Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation<br> <br> Radiation: total-body irradiation<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival at 1 Year |  | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Neutrophil Engraftment |  | 2 years | 
| Time to Platelet Engraftment |  | 1 year | 
| Incidence of Moderate to Severe Grades II to IV Graft Versus Host Disease (GVHD) at 100 Days |  | 100 days | 
| Incidence of Chronic GVHD at 1 Year |  | 1 year | 
| Immune Reconstruction/CD4+ Count at 3 Months |  | 3 months | 
| Response to Treatment |  | 2 years | 
| Immune Reconstruction/CD4+ Count at 6 Months |  | 6 months | 
| Immune Reconstruction/CD4+ Count at 1 Year |  | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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