A Trial of Reduced Intensity Conditioning and Transplantation of Haplotype Mismatched and KIR Class I Epitope-Mismatched Highly Purified CD34 Cells
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.
Interventional
Primary Purpose: Treatment
Engraftment rate
No
Sherif S. Farag, MD, PhD
Study Chair
Indiana University Melvin and Bren Simon Cancer Center
United States: Federal Government
CDR0000370797
NCT00085449
May 2006
Name | Location |
---|---|
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 |