Bone Marrow Transplant With Abatacept for Non-Malignant Diseases

Sickle Cell Disease Clinical Trial

Official title: Abatacept for Post-Transplant Immune Suppression in Children and Adolescents Receiving Allogeneic Hematopoietic Stem Cell Transplants for Non-Malignant Diseases

Status Completed

Clinical Trial Summary

This is a single arm, phase I study to assess the tolerability of abatacept when combined with cyclosporine and mycophenolate mofetil as graft versus host disease prophylaxis in children undergoing unrelated hematopoietic stem cell transplant for serious non-malignant diseases as well as to assess the immunological effects of abatacept. Participants will be followed for 2 years.

Clinical Trial Description

Allogeneic hematopoietic stem cell transplantation (HSCT) represents the only viable cure for children who suffer from a wide variety of rare, serious non-malignant diseases, such as Fanconi Anemia, Hurler syndrome, and hemophagocytic lymphohistiocytosis. A major obstacle to the success of HSCT is morbidity and mortality from graft versus host disease (GVHD), driven by donor T cells recognizing and reacting against disparate host antigens. This trial is being conducted as a step toward testing the long-term hypothesis that the costimulation blockade agent abatacept can be added to a standard post-transplant GVHD prophylaxis regimen, cyclosporine and mycophenolate mofetil, to improve disease-free survival after unrelated hematopoietic stem cell transplantation (HSCT) using reduced intensity conditioning for children with non-malignant diseases (NMD). This study will have the following Specific Aims:

Specific Aim #1: To conduct a multicenter pilot assessing the tolerability of abatacept (n=10). Patients will receive four doses (10 mg/kg IV on days -1, +5, +14 and +28), a schedule well tolerated by adolescents and adults with hematologic malignancies in a previous pilot. Abatacept will be combined with cyclosporine and mycophenolate mofetil.

Specific Aim #2: To examine the immunological effects of abatacept in this setting.

Three reduced intensity conditioning regimens that have been shown to be effective in achieving sustained engraftment in patients with non-malignant diseases are available for use, depending on the patient's disease:

• Patients with Fanconi anemia will receive fludarabine, low dose cyclophosphamide, and anti-thymocyte globulin.

• Patients with severe aplastic anemia will receive low dose total body irradiation, fludarabine, cyclophosphamide, and anti-thymocyte globulin.

• Patients with other NMD will receive either the low dose total body irradiation regimen or an alemtuzumab, fludarabine, thiotepa, and melphalan regimen. ;

Related Conditions & MeSH terms

• Anemia
• Anemia, Aplastic
• Anemia, Diamond-Blackfan
• Anemia, Sickle Cell
• beta-Thalassemia
• Chediak-Higashi Syndrome
• Chronic Granulomatous Disease
• Diamond-Blackfan Anemia
• Dyskeratosis Congenita
• Dyskeratosis-congenita
• Fanconi Anemia
• Glanzmann Thrombasthenia
• Granulomatous Disease, Chronic
• Hemophagocytic Lymphohistiocytosis
• Hurler Syndrome
• Leukocyte Adhesion Deficiency
• Lymphohistiocytosis, Hemophagocytic
• Mucopolysaccharidosis I
• Neutropenia
• Severe Aplastic Anemia
• Severe Congenital Neutropenia
• Shwachman-Diamond Syndrome
• Sickle Cell Disease
• Syndrome
• Thalassemia
• Thalassemia Major
• Wiskott-Aldrich Syndrome

• NCT number: NCT01917708
• Study type: Interventional
• Source: Emory University
• Status: Completed
• Phase: Phase 1
• Start date: January 2014
• Completion date: September 19, 2019