Non-Neoplastic Hematopoietic and Lymphoid Cell DisorderPhase 2NCT03980769
Donor Stem Cell Transplant With Treosulfan, Fludarabine, and Thiotepa in Treating Patients With Non-malignant Disorders
A Phase 2 study testing Thiotepa, Treosulfan and Fludarabine Phosphate in people with Non-Neoplastic Hematopoietic and Lymphoid Cell Disorder, run by Fred Hutchinson Cancer Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages Up to 50 years
- Conditions the study is for
- Non-Neoplastic Hematopoietic and Lymphoid Cell Disorder
- What is being tested?
- Thiotepa, Treosulfan and Fludarabine Phosphate
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- 5 May 2021to 1 Jul 2028
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 50 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 18Show fewer
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, 98109
Lauri Burroughs, 206-667-7385, lburroug@fredhutch.org
Lauri Burroughs
About this study
Official title: Allogeneic Hematopoietic Cell Transplantation for Patients With Non-Malignant Disorders Using Treosulfan, Fludarabine, and Thiotepa
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.
Read the detailed description
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.
- Being tested
- Thiotepa, Treosulfan, Fludarabine Phosphate, Rabbit Anti-Thymocyte Globulin, Allogeneic Hematopoietic Stem Cell Transplantation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ThiotepaDrug
Also called 1,1',1"-phosphinothioylidynetrisaziridine, N,N', N''-Triethylenethiophosphoramid, Oncotiotepa, STEPA
Given IV
TreosulfanDrug
Also called (S-(R*,R*))-1,2,3,4-butanetetrol, 1,4-dimethanesulfonate, [R-(R*,S*)]-, 299-75-2, 39069, Dihydroxybusulfan
Given IV
Also called 2-F-ara-AMP, 312887, 328002, 75607-67-9
Given IV
Rabbit Anti-Thymocyte GlobulinBiological
Given IV
Allogeneic Hematopoietic Stem Cell TransplantationProcedure or surgery
Also called Allogeneic Hematopoietic Cell Transplantation, Allogeneic Stem Cell Transplantation, HSC, HSCT
Undergo HCT via infusion
Bone Marrow BiopsyProcedure or surgery
Undergo bone marrow biopsy
Bone Marrow AspirationProcedure or surgery
Undergo bone marrow aspiration
Magnetic Resonance ImagingProcedure or surgery
Also called MRI, MRI Scan
Undergo MRI
Biospecimen CollectionProcedure or surgery
Undergo blood sample collection
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Engraftment failure
Will be defined as donor CD3 chimerism < 5% at 1 year after transplant.
Measured: 1 year after transplant
Secondary outcomes (6)
Overall survival
Measured: 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).
Measured: At 1 year post-transplant
Transplant-related mortality
Measured: At day 100 after transplant
Incidence of grade II-IV acute graft-versus-host disease
Measured: At day 100 after transplant
Incidence of chronic graft-versus-host disease
Measured: At 1 year after transplant
Donor chimerism CD3 & CD33
Measured: At 1 year after transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jun 2019
- Study start5 May 2021
- Primary completion1 Jul 2028 (estimated)
- Study completion1 Jul 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-Neoplastic Hematopoietic and Lymphoid Cell DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fred Hutchinson Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Lauri Burroughs, Principal investigator, Fred Hutch/University of Washington Cancer Consortium
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03980769
- Sponsor's protocol ID
- RG1005072
- Other IDs
- NCI-2019-03243, 9621
- Status last verified
- Sep 2026
- First submitted
- 6 Jun 2019
- Last updated
- 16 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No