Conditioning Regimen for Allogeneic Hematopoietic Stem-Cell Transplantation

Sickle Cell Disease Clinical Trial

Official title: 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

Clinical Trial 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.

Clinical Trial 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. ;

Related Conditions & MeSH terms

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

• NCT number: NCT03513328
• Study type: Interventional
• Source: University of Florida
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: June 15, 2018
• Completion date: February 19, 2023