A Trial of Reduced Intensity Conditioning and Transplantation of Haplotype Mismatched and KIR Class I Epitope-Mismatched Highly Purified CD34 Cells
- 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
- 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
Primary Purpose: Treatment
Sherif S. Farag, MD, PhD
Indiana University Melvin and Bren Simon Cancer Center
United States: Federal Government
|Roswell Park Cancer Institute||Buffalo, New York 14263|
|Memorial Sloan-Kettering Cancer Center||New York, New York 10021|
|University of Chicago Cancer Research Center||Chicago, Illinois 60637|
|University of Minnesota Cancer Center||Minneapolis, Minnesota 55455|
|Duke Comprehensive Cancer Center||Durham, North Carolina 27710|
|CCOP - Christiana Care Health Services||Wilmington, Delaware 19899|
|Massachusetts General Hospital Cancer Center||Boston, Massachusetts 02114|
|Holden Comprehensive Cancer Center at University of Iowa||Iowa City, Iowa 52242-1002|
|Siteman Cancer Center at Barnes-Jewish Hospital||Saint Louis, Missouri 63110|
|Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill||Chapel Hill, North Carolina 27599-7570|
|Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University||Columbus, Ohio 43210-1240|
|St. Joseph's Hospital and Medical Center||Paterson, New Jersey 07503|
|Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute||Boston, Massachusetts 02115|
|UCSF Comprehensive Cancer Center||San Francisco, California 94115|
|Mount Sinai Medical Center||New York, New York 10029|
|Wake Forest University Comprehensive Cancer Center||Winston-Salem, North Carolina 27157-1096|
|Hollings Cancer Center at Medical University of South Carolina||Charleston, South Carolina 29425|
|UNMC Eppley Cancer Center at the University of Nebraska Medical Center||Omaha, Nebraska 68198-7680|
|Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center||Los Angeles, California 90048-1865|
|Lombardi Comprehensive Cancer Center at Georgetown University Medical Center||Washington, District of Columbia 20007|
|Don Monti Comprehensive Cancer Center at North Shore University Hospital||Manhasset, New York 11030|
|Virginia Commonwealth University Massey Cancer Center||Richmond, Virginia 23298-0037|
|Moores UCSD Cancer Center||La Jolla, California 92093-0658|
|Western Pennsylvania Cancer Institute at Western Pennsylvania Hospital||Pittsburgh, Pennsylvania 15224-1791|