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.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
40
Given IV
Given IV
Given IV
Given IV
Undergo HCT via infusion
Undergo bone marrow biopsy
Undergo bone marrow aspiration
Undergo MRI
Undergo blood sample collection
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, United States
RECRUITINGEngraftment failure
Will be defined as donor CD3 chimerism \< 5% at 1 year after transplant.
Time frame: 1 year after transplant
Overall survival
Time frame: At 1 year post-transplant
Event-free survival
Defined as death due to any cause, donor lymphocyte infusion, CD34 boost, second transplant, graft rejection or graft failure, or the development of myelodysplastic syndrome or leukemia following transplant (whichever event occurs first).
Time frame: At 1 year post-transplant
Transplant-related mortality
Time frame: At day 100 after transplant
Incidence of grade II-IV acute graft-versus-host disease
Time frame: At day 100 after transplant
Incidence of chronic graft-versus-host disease
Time frame: At 1 year after transplant
Donor chimerism CD3 & CD33
Time frame: At 1 year after transplant
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