Transplantation of Umbilical Cord Blood in Patients With Hematological Malignancies Using a Treosulfan Based Preparative Regimen
I. Combined incidence of primary graft failure/rejection and secondary graft failure in Arm
1 and Arm 2.
II. Day 200 non-relapse mortality in Arm 1 and Arm 2.
I. Incidence of platelet engraftment by six months.
II. Incidence of grade II-IV and III-IV acute graft-versus-host disease (GVHD) at day 100
and one year.
III. Incidence of one year chronic GVHD.
IV. Incidence of clinically significant infections at 6 months, 1 year, 2 years.
V. Probability of one and two year survival.
VI. Incidence of one and two year relapse or disease progression.
VII. Kinetics of immune reconstitution, with both functional and quantitative assays (Fred
Hutchinson Cancer Research Center [FHCRC] only).
VIII. Examination of possible immunologic factors leading to emergence of a dominant unit
ARM I (low risk for graft failure): Patients receive a conditioning regimen comprising
fludarabine phosphate intravenously (IV) over 1 hour once daily on days -6 to -2 and
treosulfan IV over 120 minutes on days - 6 to -4. Patients undergo TBI on day -1. Patients
then undergo donor UCBT on day 0. Patients receive GVHD prophylaxis comprising cyclosporine
IV or orally (PO) 2-3 times daily on days -3 to 100, followed by a taper in the absence of
GVHD. Patients also receive mycophenolate mofetil IV 3 times daily on days 0 to 40, followed
by a taper in the absence of GVHD.
ARM II (high risk for graft failure): Patients receive a conditioning regimen, TBI, donor
UCBT, GVHD prophylaxis, and mycophenolate mofetil as in arm I.
After completion of the study treatment, patients are followed up periodically.
Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Incidence of graft failure/rejection
For both arms we will accept a graft failure rate of 5%. Arm 1 will be terminated if graft failure rates exceed 10% after maximum dose escalation. Arm 2 will be terminated if graft failure rates exceed 15% after maximum dose escalation.
By day 42
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
United States: Food and Drug Administration
|Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium||Seattle, Washington 98109|
|Oregon Health and Science University||Portland, Oregon 97201|
|University of Colorado Cancer Center - Anschutz Cancer Pavilion||Aurora, Colorado 80045|