RATIONALE: Giving low doses of chemotherapy, monoclonal antibodies, and radiation therapy before a donor peripheral 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 when they do not exactly match the patient's blood. The donated stem cells may replace the patient's immune system 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 before transplant may stop this from happening. PURPOSE: This phase I/II trial is studying the side effects of alemtuzumab, fludarabine, and melphalan with or without cyclosporine, mycophenolate mofetil, and total-body irradiation before donor peripheral blood stem cell transplant and to see how well they work in treating patients with relapsed or refractory hematologic cancer.
OBJECTIVES: * Determine the ability of a reduced-intensity conditioning regimen comprising alemtuzumab, fludarabine, and melphalan with or without cyclosporine, mycophenolate mofetil, and low-dose total body radiotherapy followed by haplotype-mismatched, KIR class I epitope-mismatched CD34-positive allogeneic peripheral blood stem cell transplantation to facilitate engraftment by day 35 post-transplantation in at least 85% of patients with relapsed, refractory, or poor-risk hematological malignancies. * Determine the risk of graft-versus-host-disease in patients treated with these regimens. * Determine, preliminarily, the efficacy of these regimens, in terms of progression-free survival, in these patients. * Correlate outcomes, engraftment, and progression-free survival with the number of detectable alloreactive natural killer cell clones before transplantation and after engraftment in patients treated with these regimens. * Determine immune reconstitution in patients treated with these regimens. OUTLINE: This is a multicenter, pilot study. Patients are initially treated with conditioning regimen A. If adequate donor engraftment is not achieved, subsequent patients are treated with conditioning regimen B. * Conditioning regimen A: Patients receive alemtuzumab IV over 2 hours on days -14 to -12; fludarabine IV over 30 minutes on days -7 to -3; and melphalan IV over 20-30 minutes on day -2. * Conditioning regimen B: Patients receive oral or IV cyclosporine twice daily and oral or IV mycophenolate mofetil twice daily on days -15 to 0. Patients also receive alemtuzumab, fludarabine, and melphalan as in conditioning regimen A. Patients undergo low-dose total body irradiation twice daily on days -2 and -1. All patients undergo allogeneic, T-cell-depleted, CD34-positive peripheral blood stem cell transplantation on day 0. Patients receive sargramostim (GM-CSF) subcutaneously beginning on day 1 and continuing until blood counts recover. Patients are followed every 3 months for 1 year and then every 6 months for 5 years. PROJECTED ACCRUAL: A total of 14-56 patients (14-28 per regimen) will be accrued for this study.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Moores UCSD Cancer Center
La Jolla, California, United States
Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center
Los Angeles, California, United States
UCSF Comprehensive Cancer Center
San Francisco, California, United States
CCOP - Christiana Care Health Services
Newark, Delaware, United States
Lombardi Comprehensive Cancer Center at Georgetown University Medical Center
Washington D.C., District of Columbia, United States
Engraftment rate
Time frame: Up to 6 years
Risk of graft-vs-host disease
Time frame: Up to 6 years
Progression-free survival (PFS)
Time frame: Up to 6 years
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University of Chicago Cancer Research Center
Chicago, Illinois, United States
Holden Comprehensive Cancer Center at University of Iowa
Iowa City, Iowa, United States
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, United States
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
Boston, Massachusetts, United States
University of Minnesota Cancer Center
Minneapolis, Minnesota, United States
...and 14 more locations