This phase II clinical trial studies how well treosulfan, thiotepa, fludarabine, and rabbit anti-thymocyte globulin (rATG) before donor stem cell transplantation works in treating patients with nonmalignant (non-cancerous) diseases. Hematopoietic cell transplantation has been shown to be curative for many patients with nonmalignant (non-cancerous) diseases such as primary immunodeficiency disorders, immune dysregulatory disorders, hemophagocytic lymphohistiocytosis, bone marrow failure syndromes, and hemoglobinopathies. Powerful chemotherapy drugs are often used to condition the patient before infusion of the new healthy donor cells. The purpose of the conditioning therapy is to destroy the patient's abnormal bone marrow which doesn't work properly in order to make way for the new healthy donor cells which functions normally. Although effective in curing the patient's disease, many hematopoietic cell transplantation regimens use intensive chemotherapy which can be quite toxic, have significant side effects, and can potentially be life-threatening. Investigators are investigating whether a new conditioning regimen that uses less intensive drugs (treosulfan, thiotepa, and fludarabine phosphate) results in new blood-forming cells (engraftment) of the new donor cells without increased toxicities in patients with nonmalignant (non-cancerous) diseases.
Additional locations may be listed on ClinicalTrials.gov for NCT03980769.
Locations matching your search criteria
United States
Washington
Seattle
Fred Hutch/University of Washington/Seattle Children's Cancer ConsortiumStatus: Active
Contact: Lauri M Burroughs
Phone: 206-667-7385
PRIMARY OBJECTIVE:
I. To evaluate the preliminary efficacy as defined by engraftment, of a regimen consisting of treosulfan, fludarabine phosphate (fludarabine), and thiotepa followed by allogeneic hematopoietic cell transplant (HCT) in patients with nonmalignant disorders.
SECONDARY OBJECTIVES:
I. To estimate overall survival 1-year after HCT.
II. To estimate event-free survival at 1-year after HCT.
III. To estimate day 100 transplant related mortality after HCT.
IV. To evaluate the incidence of grade II-IV acute and chronic graft-versus-host disease.
V. To evaluate donor chimerism CD3 & CD33 at 1 year after HCT.
EXPLORATORY OBJECTIVE:
I. Pharmacokinetic parameters of treosulfan and treosulfan monoepoxide.
OUTLINE:
Patients receive thiotepa intravenously (IV) twice daily (BID) over 2 hours on day -7, treosulfan IV over 120 minutes on days -6 to -4, fludarabine phosphate IV over 60 minutes on days -6 to -2, and rabbit anti-thymocyte globulin IV over 4-6 hours on days -4 to -2. Patients then undergo allogeneic hematopoietic cell transplant via infusion on day 0. Patients may also undergo bone marrow biopsy and aspiration and magnetic resonance imaging (MRI) as clinically indicated and blood sample collection on study.
After completion of study treatment, patients are followed up at 1 year and then annually thereafter.
Lead OrganizationFred Hutch/University of Washington/Seattle Children's Cancer Consortium
Principal InvestigatorLauri M Burroughs
