NCT03980769 · Fred Hutchinson Cancer Center
Donor Stem Cell Transplant With Treosulfan, Fludarabine, and Thiotepa in Treating Patients With Non-malignant Disorders
What this study is about
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.
View original scientific description
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.
Interventions
DRUG
Thiotepa
Given IV
DRUG
Treosulfan
Given IV
DRUG
Fludarabine Phosphate
Given IV
BIOLOGICAL
Rabbit Anti-Thymocyte Globulin
Given IV
PROCEDURE
Allogeneic Hematopoietic Stem Cell Transplantation
Undergo HCT via infusion
PROCEDURE
Bone Marrow Biopsy
Undergo bone marrow biopsy
PROCEDURE
Bone Marrow Aspiration
Undergo bone marrow aspiration
PROCEDURE
Magnetic Resonance Imaging
Undergo MRI
PROCEDURE
Biospecimen Collection
Undergo blood sample collection
Primary outcome measures
Engraftment failure
Time frame: 1 year after transplant
Will be defined as donor CD3 chimerism \< 5% at 1 year after transplant.
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
Inclusion criteria
- Patient with nonmalignant disease treatable by allogeneic HCT
- Patient with a nonmalignant disease that is not clearly defined (a patient with a non-malignant disease for whom genetic testing has been done and 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)
- Age \< 50 years
- 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 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 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 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
- Evidence of synthetic dysfunction or severe cirrhosis requiring deferral of conditioning as recommended by a gastroenterology specialist
- Active infectious disease requiring deferral of conditioning as recommended by an infectious disease specialist
- Positive for HIV (human immunodeficiency virus)
- Females who are pregnant or breast-feeding
- 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
Where
- Seattle, Washington
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Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Mar 12, 2026 · Source of record for eligibility and locations