Non-Myeloablative Allogeneic Hematopoietic Cell Transplantation For Patients With Disease Relapse Or Myelodysplasia After Prior Autologous Transplantation
- Determine the feasibility of non-myeloablative allogeneic hematopoietic stem cell
transplantation by demonstrating that the risk of treatment-related mortality during
the first 6 months is an acceptable rate of less than 40% in patients with relapsed
hematologic malignancies after prior high-dose chemotherapy and autologous stem cell
- Determine the response rates (disease-specific partial and complete response) in
patients treated with this regimen.
- Determine the 6-month and 12-month probabilities of response in patients treated with
- Determine the distribution of time-to-progression in patients responding to this
- Determine the percent donor chimerism in patients treated with this regimen.
- Determine the risk of acute and chronic graft-vs-host disease in patients treated with
- Determine the toxic effects of this regimen in these patients.
- Determine the disease-free and overall survival of patients treated with this regimen.
OUTLINE: This is an open-label study.
- Preparative Regimen: Patients receive fludarabine IV over 30 minutes on days -7 to -3
and busulfan IV over 2 hours every 6 hours (for a total of 8 doses) on days -4 and -3.
- Graft vs Host Disease (GVHD) Prophylaxis: Patients who have an HLA-identical donor
receive oral (or IV if unable to tolerate oral administration) tacrolimus twice daily
on days -1 to 90 followed by a taper^* until day 150 and methotrexate IV on days 1, 3,
and 6. Patients with a matched related or matched unrelated donor receive oral (or IV
if unable to tolerate oral administration) tacrolimus twice daily on days -1 to 180
followed by a taper^* as tolerated; methotrexate IV on days 1, 3, 6, and 11; oral
mycophenolate mofetil twice daily on days -2 to 60 followed by a taper; and rabbit
anti-thymocyte globulin IV over 4-6 hours on days -4 to -1 (for a total of 4 doses).
NOTE: *Tacrolimus may be tapered on days 60-90 if donor chimerism of CD3+ cells is less than
50% at day 60 or patient has progressive disease
- Allogeneic Stem Cell Transplantation: Patients undergo allogeneic bone marrow or
peripheral blood stem cell transplantation on days 0 and 1. Patients then receive
filgrastim (G-CSF) subcutaneously daily beginning on day 7 and continuing until blood
- Donor Lymphocyte Infusion (DLI): After day 180 (or day 210 for patients without an
HLA-identical donor), patients with stable or progressive disease and no active GVHD
may receive up to 3 DLIs every 8 weeks.
Patients are followed within 2-3 months, every 3 months for 2 years, and then every 6 months
for 3 years.
PROJECTED ACCRUAL: A total of 20-80 patients will be accrued for this study within 10-40
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
6 months post transplant
Asad Bashey, MD, PhD
University of California, San Diego
United States: Federal Government
|Roswell Park Cancer Institute||Buffalo, New York 14263|
|CCOP - Christiana Care Health Services||Wilmington, Delaware 19899|
|Siteman Cancer Center at Barnes-Jewish Hospital||Saint Louis, Missouri 63110|
|Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University||Columbus, Ohio 43210-1240|
|Rebecca and John Moores UCSD Cancer Center||La Jolla, California 92093-0658|
|Wake Forest University Comprehensive Cancer Center||Winston-Salem, North Carolina 27157-1096|
|Massey Cancer Center at Virginia Commonwealth University||Richmond, Virginia 23298-0037|
|Cancer Institute of New Jersey at the Cooper University Hospital - Voorhees||Camden, New Jersey 08103|
|Beebe Medical Center||Lewes, Delaware 19958|
|St. Francis Hospital||Wilmington, Delaware 19805|
|Union Hospital Cancer Center at Union Hospital||Elkton MD, Maryland 21921|
|Western Pennsylvania Cancer Institute at Western Pennsylvania Hospital||Pittsburgh, Pennsylvania 15224-1791|