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

NCT03980769 | Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: RG1005072NCI-2019-032439621
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Non-Neoplastic Hematopoietic and Lymphoid Cell Disorder

Outcome Measures

Primary Outcomes (1)

• Engraftment failure

  Will be defined as donor CD3 chimerism \< 5% at 1 year after transplant.

  1 year after transplant

Secondary Outcomes (6)

• Overall survival

  At 1 year post-transplant

• Event-free survival

  At 1 year post-transplant

• Transplant-related mortality

  At day 100 after transplant

• Incidence of grade II-IV acute graft-versus-host disease

  At day 100 after transplant

• Incidence of chronic graft-versus-host disease

  At 1 year after transplant

Study Arms (1)

Treatment (chemotherapy, transplant)

EXPERIMENTAL

Patients receive thiotepa IV 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 MRI as clinically indicated and blood sample collection on study.

Drug: Thiotepa; Drug: Treosulfan; Drug: Fludarabine Phosphate; Biological: Rabbit Anti-Thymocyte Globulin; Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Procedure: Bone Marrow Biopsy; Procedure: Bone Marrow Aspiration; Procedure: Magnetic Resonance Imaging; Procedure: Biospecimen Collection

Interventions

Thiotepa DRUG

Given IV

Also known as: 1,1',1"-phosphinothioylidynetrisaziridine, N,N', N''-Triethylenethiophosphoramid, Oncotiotepa, STEPA, Tepadina, TESPA, Tespamin, Tespamine, Thio-Tepa, Thiofosfamide, Thiofozil, Thiophosphamide, Thiophosphoramide, Thiotef, Tifosyl, TIO TEF, Triethylene thiophosphoramide, Triethylenethiophosphoramide, TSPA

Treatment (chemotherapy, transplant)

Treosulfan DRUG

Given IV

Also known as: (S-(R*,R*))-1,2,3,4-butanetetrol, 1,4-dimethanesulfonate, [R-(R*,S*)]-, 299-75-2, 39069, Dihydroxybusulfan, Ovastat, Treosulphan, Tresulfon

Treatment (chemotherapy, transplant)

Fludarabine Phosphate DRUG

Given IV

Also known as: 2-F-ara-AMP, 312887, 328002, 75607-67-9, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara, Fludarabine-5'-Monophosphate

Treatment (chemotherapy, transplant)

Rabbit Anti-Thymocyte Globulin BIOLOGICAL

Given IV

Treatment (chemotherapy, transplant)

Bone Marrow Biopsy PROCEDURE

Undergo bone marrow biopsy

Treatment (chemotherapy, transplant)

Allogeneic Hematopoietic Stem Cell Transplantation PROCEDURE

Undergo HCT via infusion

Also known as: Allogeneic Hematopoietic Cell Transplantation, Allogeneic Stem Cell Transplantation, HSC, HSCT

Treatment (chemotherapy, transplant)

Bone Marrow Aspiration PROCEDURE

Undergo bone marrow aspiration

Treatment (chemotherapy, transplant)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: MRI, MRI Scan

Treatment (chemotherapy, transplant)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Treatment (chemotherapy, transplant)

Eligibility Criteria

• Age: Up to 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

RECRUITING

MeSH Terms

Interventions

Thiotepa; treosulfan; fludarabine phosphate; Antilymphocyte Serum; Magnetic Resonance Spectroscopy

Intervention Hierarchy (Ancestors)

Phosphoramides; Organophosphorus Compounds; Organic Chemicals; Triethylenephosphoramide; Aziridines; Azirines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques

Study Officials

• Lauri Burroughs

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lauri Burroughs

CONTACT

206-667-7385; lburroug@fredhutch.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 6, 2019
• First Posted: June 10, 2019
• Study Start: May 5, 2021
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): July 1, 2028
• Last Updated: March 12, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)