Reduced-Intensity Allogeneic Hematopoietic Cell Transplantation as Second Transplantation for Patients With Disease Relapse or Myelodysplasia After Prior Autologous Transplantation
- To demonstrate the efficacy of performing reduced-intensity conditioning allogeneic
hematopoietic cell transplantation in patients with relapsed hematologic malignancies
or secondary myelodysplasia after completion of prior high-dose chemotherapy and
autologous hematopoietic stem cell transplantation.
- To compare the strategy of this regimen with the strategy used in CALGB-100002.
- To describe the response rate at 6 and 12 months in patients treated with this regimen.
- To describe the time-to-progression in patients treated with this regimen.
- To determine the ability to use pharmacokinetic-directed busulfan to achieve AUC within
20% of target AUC in > 80% of patients.
- To determine percent of donor chimerism in T-cell, myeloid and B-cell populations
achieved with this regimen compared with CALGB-100002.
- To determine the risk of acute and chronic graft-versus-host disease and other
toxicities of this regimen in these patients.
- To describe the overall survival and disease-free survival of patients treated on this
- To determine the rate of viral, bacterial, and fungal opportunistic infections
occurring in the first year after transplantation compared with CALGB-100002.
OUTLINE: This is a multicenter study.
- Preparative Regimen:
- Busulfan test dose: Patients receive busulfan IV over 45 minutes once during days
-14 and -9.
- Busulfan treatment dose: Patients receive fludarabine phosphate IV over 30 minutes
on days -7 to -3 and busulfan IV over 3 hours on days -6 to -3.
- Graft-vs-Host Disease (GVHD) Prophylaxis:
- HLA-identical donor: Patients receive antithymocyte globulin IV over 6-10 hours on
days -6 to -5; oral tacrolimus twice daily on days -2 to 90 followed by a taper*
as tolerated until day 150 or 180; and methotrexate IV on days 1, 3, and 6.
NOTE: * Tacrolimus may be tapered on days 60-90 if donor chimerism of CD3+ cells is < 50% at
day 60 or patient has progressive disease.
- Matched-unrelated donor: Patients receive antithymocyte globulin, tacrolimus, and
methotrexate as in HLA-identical donor regimen. Patients also receive oral
mycophenolate mofetil twice daily on days 0 to 60.
- Allogeneic Stem Cell Transplantation: Patients undergo allogeneic peripheral blood
stem cell transplantation on days 0 and 1. Patients then receive filgrastim
subcutaneously daily beginning on day 7 and continuing until blood counts recover.
- 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.
Blood samples are collected at baseline and then periodically during study therapy for
After completion of study therapy, patients are followed up every 3 months for 2 years and
then every 6 months for up to 5½ years.
Masking: Open Label, Primary Purpose: Treatment
Event-free survival (EFS)
Asad Bashey, MD, PhD
Blood and Marrow Transplant Group of Georgia
United States: Federal Government
|CCOP - Christiana Care Health Services||Wilmington, Delaware 19899|
|Florida Hospital Cancer Institute at Florida Hospital Orlando||Orlando, Florida 32803-1273|
|Wake Forest University Comprehensive Cancer Center||Winston-Salem, North Carolina 27157-1096|
|Greenebaum Cancer Center at University of Maryland Medical Center||Baltimore, Maryland 21201|
|New York Weill Cornell Cancer Center at Cornell University||New York, New York 10021|
|Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis||St. Louis, Missouri 63110|
|Cancer Institute of New Jersey at Cooper - Voorhees||Voorhees, New Jersey 08043|
|Tunnell Cancer Center at Beebe Medical Center||Lewes, Delaware 19958|
|Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center||Columbus, Ohio 43210-1240|
|Union Hospital of Cecil County||Elkton MD, Maryland 21921|