- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03980769
Donor Stem Cell Transplant With Treosulfan, Fludarabine, and Thiotepa in Treating Patients With Non-malignant Disorders
Allogeneic Hematopoietic Cell Transplantation for Patients With Non-Malignant Disorders Using Treosulfan, Fludarabine, and Thiotepa
Study Overview
Status
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.
After completion of study treatment, patients are followed up at 1 year and then annually thereafter.
Study Type
Enrollment (Estimated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Lauri Burroughs
- Phone Number: 206-667-2396
- Email: lburroug@fredhutch.org
Study Locations
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-
Washington
-
Seattle, Washington, United States, 98109
- Recruiting
- Fred Hutch/University of Washington Cancer Consortium
-
Contact:
- Lauri Burroughs
- Phone Number: 206-667-2396
- Email: lburroug@fredhutch.org
-
Principal Investigator:
- Lauri Burroughs
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Treatment (chemotherapy, transplant)
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.
|
Given IV
Other Names:
Given IV
Other Names:
Given IV
Other Names:
Given IV
Undergo HCT via infusion
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Engraftment failure
Time Frame: 1 year after transplant
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Will be defined as donor CD3 chimerism < 5% at 1 year after transplant.
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1 year after transplant
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall survival
Time Frame: At 1 year post-transplant
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At 1 year post-transplant
|
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Event-free survival
Time Frame: At 1 year post-transplant
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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).
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At 1 year post-transplant
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Transplant-related mortality
Time Frame: At day 100 after transplant
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At day 100 after transplant
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Incidence of grade II-IV acute graft-versus-host disease
Time Frame: At day 100 after transplant
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At day 100 after transplant
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Incidence of chronic graft-versus-host disease
Time Frame: At 1 year after transplant
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At 1 year after transplant
|
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Donor chimerism CD3 & CD33
Time Frame: At 1 year after transplant
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At 1 year after transplant
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Lauri Burroughs, Fred Hutch/University of Washington Cancer Consortium
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Hematologic Diseases
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Fludarabine
- Fludarabine phosphate
- Thiotepa
- Busulfan
- Thymoglobulin
- Antilymphocyte Serum
- Treosulfan
Other Study ID Numbers
- RG1005072
- NCI-2019-03243 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
- 9621 (Other Identifier: Fred Hutch/University of Washington Cancer Consortium)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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