Donor Stem Cell Transplant With Treosulfan, Fludarabine, and Thiotepa in Treating Patients With Non-malignant Disorders

  • End date
    Jul 1, 2027
  • participants needed
  • sponsor
    Fred Hutchinson Cancer Center
Updated on 29 April 2022
treatment regimen
bone marrow procedure
primary cancer


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-cancerious) 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.



Patients receive thiotepa intravenously (IV) twice daily (BID) on day -7, treosulfan IV on days -6 to -4, fludarabine phosphate IV on days -6 to -2, and rabbit anti-thymocyte globulin IV on days -4 to -2. Patients then undergo allogeneic hematopoietic cell transplant via infusion on day 0.

After completion of study treatment, patients are followed up at 1 year and then annually thereafter.

Condition Non-Neoplastic Hematologic and Lymphocytic Disorder
Treatment fludarabine phosphate, allogeneic hematopoietic stem cell transplantation, treosulfan, thiotepa, Rabbit Anti-thymocyte Globulin
Clinical Study IdentifierNCT03980769
SponsorFred Hutchinson Cancer Center
Last Modified on29 April 2022


Yes No Not Sure

Inclusion Criteria

Patient with nonmalignant disease treatable by allogenic HCT
Patient with a nonmalignant disease that is not clearly defined (a patient with a non-malignant disease HCT for whom a genetic mutation responsible for their non-malignant disease phenotype has not been identified) are eligible for the study following discussion with and approval by the protocol principal investigator (PI) (Dr. Lauri Burroughs)
DONOR: Human leukocyte antigen (HLA)-identical related donor OR unrelated donor matched for HLA-A, B, C, DRB1 and DQB1 or mismatched for a single allele at HLA-A, B, C, or a single DQB1 antigen or allele mismatch by high resolution deoxyribonucleic acid (DNA) typing
DONOR: Bone marrow is the preferred cell source (when feasible). However, peripheral blood stem cells (PBSC) is also allowed and the PI may determine if PBSC is preferred for certain patients
The recommended total nucleated cell count (TNC) for bone marrow grafts is >= 4.0 x 10^8 TNC/kg (actual recipient weight)
The recommended CD34 cell count for PBSC grafts is >= 5 x 10^6 CD34/kg (actual recipient weight) and the recommended maximum CD34 cell count for PBSC grafts is 10 x 10^6 CD34/kg (actual recipient weight)
DONOR: HLA-matched sibling bone marrow in combination with HLA-matched sibling
umbilical cord blood if the HLA-matched sibling umbilical cord blood was
collected and stored. The HLA-matched sibling bone marrow and cord blood would
be matched for HLA-A, B, C, DRB1 and DQB1

Exclusion Criteria

Patients with idiopathic aplastic anemia and Fanconi anemia; patients with aplastic anemia associated with paroxysmal nocturnal hemoglobinuria (PNH) or inherited marrow failure syndromes (except Fanconi anemia) will be allowed
Impaired pulmonary function as evidenced by carbon monoxide diffusing capability (DLCO) corrected < 50% of predicted (or, if unable to perform pulmonary function tests, then oxygen [O2] saturation < 92% on room air)
Impaired cardiac function as evidenced by ejection fraction < 35% (or, if unable to obtain ejection fraction, shortening fraction of < 26%) or cardiac insufficiency requiring treatment or symptomatic coronary artery disease. Patients with a shortening fraction of < 26% may be enrolled if approved by a cardiologist
Impaired renal function as evidenced by
Estimated creatinine clearance < 60 mL/min/1.73m^2 using either the Chronic Kidney Disease Epidemiology Collaboration (CKD EPI) equation for adult patients (>= 18 years old), or the updated Schwartz formula for pediatric patients (< 18 years old). If the estimated creatinine clearance is < 60 mL/min/1.73m^2, then renal function must be measured by 24-hour creatinine clearance, Iothalamate, Iohexol or nuclear GFR and the patient is excluded if their measured creatinine clearance is < 50 mL/min/1.73 m^2, OR
Serum creatinine > 2 x upper limit of normal, OR
Dialysis dependent
Active infectious disease requiring deferral of conditioning as recommended by an infectious disease specialist
Positive for HIV (human immunodeficiency virus)
Evidence of synthetic dysfunction or severe cirrhosis requiring deferral of
Females who are pregnant or breast-feeding
conditioning as recommended by a gastroenterology specialist
Known hypersensitivity to treosulfan, fludarabine, and/or thiotepa
DONOR: Donors deemed unable to undergo marrow harvesting of PBSC mobilization and leukapheresis
DONOR: HIV-positive donors
DONOR: Donors with active infectious hepatitis
DONOR: Female donor with positive pregnancy test
DONOR: Donors are excluded if the patient has an identified antibody against a donor-specific HLA locus as specified in standard practice
DONOR: HLA-matched sibling cord blood units that have not passed donor screening for infectious disease markers as recommended by the National Marrow Donor Project (NMDP) will not be used unless a waiver is signed by the clinical attending allowing use of cord blood unit. Cord blood units are presumed to be cytomegalovirus (CMV) negative regardless of serologic testing due to passive transmission of maternal CMV antibodies
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