Chemotherapy, Total-Body Irradiation, Rituximab, and Donor Stem Cell Transplant in Treating Patients With B-Cell Non-Hodgkin's Lymphoma or Chronic Lymphocytic Leukemia
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.
Description
OBJECTIVES:
Primary
- Determine the overall and event-free survival at 1 year in patients with B-cell non-Hodgkin's lymphoma or chronic lymphocytic leukemia treated with a nonmyeloablative conditioning regimen, rituximab, and allogeneic hematopoietic stem cell transplantation.
Secondary
- Determine the speed of neutrophil and platelet recovery in patients treated with this regimen.
- Determine the incidence and speed of donor-derived engraftment in these patients.
- Determine the incidence and severity of acute graft versus host disease (GVHD) at 100 days in patients treated with this regimen.
- Determine the incidence and severity of chronic GVHD at 1 year in patients treated with this regimen.
- Correlate the incidence of serious infectious complications with immune recovery in patients treated with this regimen.
- Determine the response in patients treated with this regimen.
- Determine the incidence of transplant-related mortality at 100 and 180 days in these patients.
- Determine the incidence of malignant relapse or disease progression at 1 and 2 years in these patients.
- Determine the probabilities of overall and event-free survival at 2 years in patients treated with this regimen.
OUTLINE: Patients are stratified according to donor type (HLA-matched related vs HLA-matched unrelated or single HLA allele-disparate related or unrelated).
- Rituximab therapy: Patients receive rituximab IV on day -8 or -7 and on days 21, 28, 35, and 42.
- Nonmyeloablative conditioning: Patients receive fludarabine phosphate IV over 30 minutes on days -6 to -2, cyclophosphamide IV on day -6, and anti-thymocyte globulin (ATG)* IV over 4-6 hours on days -3 and/or -2. Patients undergo total-body irradiation on day -1.
NOTE: *Patients with HLA-matched sibling donors do not receive ATG.
- Allogeneic hematopoietic stem cell transplantation (HSCT): Patients undergo filgrastim (G-CSF)-mobilized allogeneic HSCT on day 0. Patients receive filgrastim (G-CSF) IV or subcutaneously beginning on day 7 and continuing until blood counts recover.
- Graft versus host disease prophylaxis: Patients receive cyclosporine IV over 2-4 hours or orally twice daily on days -3 to 100 followed by a taper and mycophenolate mofetil IV or orally twice daily on days -3 to 45 followed by a taper, in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed every 3-6 months for 2 years and then annually thereafter.
PROJECTED ACCRUAL: A total of 60 patients will be accrued for this study.
Study Design
Masking: Open Label, Primary Purpose: Treatment
Conditions
Leukemia
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
Location
Memorial Sloan-Kettering Cancer Center
New York
New York
United States
10065
Status
Recruiting
Source
National Cancer Institute (NCI)
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT00425802
- Information obtained from ClinicalTrials.gov on July 15, 2010
Published on BioPortfolio: 2014-08-27T03:40:33-0400
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Medical and Biotech [MESH] Definitions
Graft Enhancement, Immunologic
The induction of prolonged survival and growth of allografts of either tumors or normal tissues which would ordinarily be rejected. It may be induced passively by introducing graft-specific antibodies from previously immunized donors, which bind to the graft's surface antigens, masking them from recognition by T-cells; or actively by prior immunization of the recipient with graft antigens which evoke specific antibodies and form antigen-antibody complexes which bind to the antigen receptor sites of the T-cells and block their cytotoxic activity.
Graft Vs Tumor Effect
Immunological rejection of tumor tissue/cells following bone marrow transplantation.
T-lymphocytes, Cytotoxic
Immunized T-lymphocytes which can directly destroy appropriate target cells. These cytotoxic lymphocytes may be generated in vitro in mixed lymphocyte cultures (MLC), in vivo during a graft-versus-host (GVH) reaction, or after immunization with an allograft, tumor cell or virally transformed or chemically modified target cell. The lytic phenomenon is sometimes referred to as cell-mediated lympholysis (CML). These CD8-positive cells are distinct from NATURAL KILLER CELLS and NATURAL KILLER T-CELLS. There are two effector phenotypes: TC1 and TC2.
Host Vs Graft Reaction
The immune responses of a host to a graft. A specific response is GRAFT REJECTION.
Rho(d) Immune Globulin
Immunizing agent containing IMMUNOGLOBULIN G anti-Rho(D) used for preventing Rh immunization in Rh-negative individuals exposed to Rh-positive red blood cells.
