NCT03513328

Conditioning Regimen for Allogeneic Hematopoietic Stem-Cell Transplantation

PEDS024, Phase I/II Feasibility Study of Busulfan Fludarabine and Thiotepa Conditioning Regimen for Allogeneic Hematopoietic Stem-Cell Transplantation (HSCT) for Children With Non-Malignant Disorders

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 6 (actual)
• Sponsor: University of Florida · Academic / Other
• Sex: All
• Age: 3 Months – 39 Years
• Healthy volunteers: Not accepted

Summary

In this study, the investigators test 2 dose levels of thiotepa (5 mg/kg and 10 mg/kg) added to the backbone of targeted reduced dose IV busulfan, fludarabine and rabbit anti-thymocyte globulin (rATG) to determine the minimum effective dose required for reliable engraftment for subjects undergoing hematopoietic stem cell transplantation for non-malignant disease.

Detailed description

Hematopoietic stem cell transplantation is the only curative choice for a number of inherited bone marrow failure syndromes, hemoglobinopathies, metabolic disorders and primary immune deficiencies. While survival of these patients is typically better than survival of patients with malignancies, toxicities of conditioning regimens and failure of engraftment remain challenges. Most children with non-malignant disorders present with normocellular or even hypercellular bone marrow, posing a barrier to engraftment and requiring intensive conditioning. Commonly used backbone of busulfan and fludarabine, although well tolerated, results in variable engraftment, in particular with mismatched unrelated donors and cord blood recipients. In this study, the investigators test 2 dose levels of thiotepa (5 mg/kg and 10 mg/kg) added to the backbone of targeted reduced dose IV busulfan, fludarabine and rabbit anti-thymocyte globulin (rATG) in order to determine the minimum effective dose required for reliable engraftment. Subjects are stratified in groups A and B based the risk of graft failure.

Conditions

• Bone Marrow Failure Syndrome
• Thalassemia
• Sickle Cell Disease
• Diamond Blackfan Anemia
• Acquired Neutropenia in Newborn
• Acquired Anemia Hemolytic
• Acquired Thrombocytopenia
• Hemophagocytic Lymphohistiocytoses
• Wiskott-Aldrich Syndrome
• Chronic Granulomatous Disease
• Common Variable Immunodeficiency
• X-linked Lymphoproliferative Disease
• Severe Combined Immunodeficiency
• Hurler Syndrome
• Mannosidosis
• Adrenoleukodystrophy

Interventions

Type	Name	Description
DRUG	Thiotepa--single daily dose	Conditioning regimen for hematopoietic stem-cell transplant. Single daily IV dose of Thiotepa at 5 mg/kg.
DRUG	Thiotepa--escalated dose	Twice daily IV dose of Thiotepa at 5 mg/kg, twelve hours apart, 10mg/kg total.

Timeline

• Start date: 2018-06-15
• Primary completion: 2022-02-17
• Completion: 2023-02-19
• First posted: 2018-05-01
• Last updated: 2023-09-15
• Results posted: 2023-09-15

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study