A Multi-Center Phase II Study of Nonmyeloablative Conditioning With TBI and Fludarabine for HLA-Matched Related Hematopoietic Cell Transplantation for Treatment of Chronic Myeloid Leukemia in Chronic and Accelerated Phase
- Determine the disease-free survival rate in patients with chronic or accelerated phase
chronic myelogenous leukemia that failed or inadequately responded to prior imatinib
mesylate treated with nonmyeloablative conditioning comprising fludarabine and low-dose
total-body irradiation followed by allogeneic peripheral blood stem cell
- Determine the complete cytogenetic and molecular response rates in patients treated
with this regimen.
- Determine overall survival of patients treated with this regimen.
- Determine non-relapse mortality in patients treated with this regimen.
- Determine the incidence of serious infection, graft-versus-host disease, and
myelosuppression in patients treated with this regimen.
OUTLINE: This is a multicenter study.
- Conditioning treatment: Patients receive fludarabine IV on days -4 to -2. Patients
undergo low-dose total-body irradiation (TBI) on day 0.
- Allogeneic peripheral blood stem cell transplantation: After TBI, patients undergo
allogeneic peripheral blood stem cell transplantation on day 0.
- Immunosuppression: Patients receive oral cyclosporine twice daily on days -3 to 56
followed by a taper to day 180 in the absence of graft-versus-host disease (GVHD).
Patients also receive oral mycophenolate mofetil twice daily on days 0-27.
- Post-transplant treatment: Patients experiencing disease persistence or progression AND
low donor chimerism discontinue immunosuppression. Patients with disease persistence or
progression after discontinuing immunosuppression receive oral imatinib mesylate once
daily. Patients who have disease improvement after day 28 of imatinib mesylate
treatment AND who have no evidence of disease after day 84 of imatinib mesylate
treatment continue imatinib mesylate in the absence of disease progression or
unacceptable toxicity. Patients who fail to improve after day 28 of imatinib mesylate
treatment OR who have residual disease after day 84 of imatinib mesylate treatment
receive donor lymphocytes IV over 15-30 minutes once every 1-4 months for up to 4
infusions. Patients ineligible to receive donor lymphocytes (e.g., patients with
evidence of GVHD) receive interferon alfa subcutaneously 3 times a week for up to 12
months in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed at 6, 9, 12, 18, and 24 months,
and then annually for 5 years.
PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.
Masking: Open Label, Primary Purpose: Treatment
Brenda Sandmaier, MD
Fred Hutchinson Cancer Research Center
United States: Federal Government
|Fred Hutchinson Cancer Research Center||Seattle, Washington 98109|
|City of Hope Comprehensive Cancer Center||Duarte, California 91010|
|Seattle Cancer Care Alliance||Seattle, Washington 98109|