Allogeneic Hematopoietic Cell Transplantation for Patients With Nonmalignant Inherited Disorders Using a Treosulfan Based Preparative Regimen.
I. To evaluate within the limits of a phase II study, the preliminary efficacy, as defined
by engraftment, of a regimen consisting of treosulfan and fludarabine followed by allogeneic
hematopoietic cell transplantation (HCT) in patients with nonmalignant inherited disorders.
I. To evaluate the incidence of non-relapse mortality 200 days and 1 year post-HCT.
II. To evaluate the incidence of grade II-IV acute graft-versus-host disease (GVHD).
III. To evaluate the incidence of chronic GVHD as defined as those patients requiring
IV. To evaluate donor chimerism on days +28 and +100.
V. To assess disease response following HCT.
VI. To evaluate immune reconstitution following HCT.
VII. To evaluate the incidence of infections.
VIII. To evaluate overall survival.
CONDITIONING REGIMEN: Patients receive treosulfan intravenously (IV) over 2 hours on days -6
to -4 and fludarabine IV over 1 hour on days -6 to -2. Patients receive anti-thymocyte
globulin IV over 4-6 hours on days -4 to -2. Patients undergoing umbilical cord blood
transplantation will also receive low dose total-body irradiation on day -1.
TRANSPLANTATION: Patients will receive either bone marrow, peripheral blood stem cells
(PBSC), or umbilical cord blood from the donor on day 0. The use of either bone marrow,
PBSC, or umbilical cord blood will depend on the donor status.
IMMUNOSUPPRESSION: Patients will receive a combination of immunosuppressive medications to
try and prevent graft-versus-host disease. If patients undergo bone marrow or PBSC
transplantation, tacrolimus and methotrexate will be used. If patients undergo cord blood
transplantation, cyclosporine and mycophenolate mofetil will be used. In general, patients
will receive immunosuppression until at least 180 days after transplantation; however they
could be on immunosuppression longer if they develop graft versus host disease.
After completion of study treatment, patients are followed up periodically for 5 years.
Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Preliminary efficacy as defined by engraftment of a regimen consisting of treosulfan and fludarabine followed by allogeneic HCT in patients with nonmalignant inherited disorders
1 year following transplant
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|
|Children's Hospital of Wisconsin||Milwaukee, Wisconsin 53201|
|Oregon Health and Science University||Portland, Oregon 97201|
|Monroe Carell Jr. Children's Hospital at Vanderbilt||Nashville, Tennessee 37232|