Haploidentical Transplant for People With Chronic Granulomatous Disease (CGD) Using Alemtuzumab, Busulfan and TBI With Post-Transplant Cyclophosphamide

Chronic Granulomatous Disease Clinical Trial

Official title: Haploidentical Transplant for Patients With Chronic Granulomatous Disease (CGD) Using Alemtuzumab, Busulfan and TBI With Post-Transplant Cyclophosphamide

Status Recruiting

Clinical Trial Summary

Background: CGD causes infections and inflammation. The only cure currently is a bone marrow transplant. Most often a perfectly matched bone marrow donor is used. Researchers want to see if they can lower the risks of using a mismatched donor. Objectives: To see if it is safe to use a related bone marrow donor who is only a partial match to a person with CGD. To see how well drugs given to a person before and after transplant help the body accept the transplant. Eligibility: People ages 4-65 with CGD for whom stem cell transplant may be a cure and who do not have a perfectly matched donor, related or unrelated. Design: Participants will be screened with: Medical history Physical exam Blood tests Participants will be admitted to the hospital about 2 weeks before the transplant. They will have blood, urine, breathing, and heart tests. They may have CT and/or MRI scans. They will have a needle inserted into their hipbone to remove marrow. They will have dental, neurologic, and psychologic tests. They will have a central catheter placed: A line will be placed into a vein in their upper chest. They will get drugs, chemotherapy, and radiation to prepare for the transplant. Participants will receive the donated cells through their catheter. The cells will be from one of their relatives. Participants will stay in the hospital about 6 weeks after the transplant. After they leave the hospital, participants will have to stay in the area with visits about 2 times a week for approximately 100 days post transplant. Then visits will be every 3 to 6 months for 2 years. Then visits will be once a year.

Clinical Trial Description

Allogeneic transplant using human leukocyte antigen (HLA) matched donors, both related and unrelated, has proven curative for patients with various immunodeficiencies, including those with ongoing infections. However, donor availability remains a limiting factor in the application of this treatment modality. For this protocol, a haploidentical donor is a related donor with more than 1 HLA antigen mismatch. The use of haploidentical related donors has in the past been fraught with a greater rate of complications related to both higher rates of graft versus host disease (GvHD) and delayed immunorecovery. Newer transplant regimens appear to have diminished these risks and improved outcomes. We propose using a reduced intensity novel conditioning regimen using alemtuzumab, targeted busulfan, and low dose total body irradiation (see schema below) followed by post-transplant cyclophosphamide for patients with chronic granulomatous disease (CGD) who do not have an HLA matched donor but whose circumstances necessitate the use of a potentially curative, albeit high-risk treatment modality. However, patients with CGD have high rates of Crohn s Disease-like inflammatory bowel disease, predominantly colitis, where uncontrolled severe IBD may increase risk of GvHD. For this reason, the first 10 patients enrolled will exclude those deemed to have intestinal inflammation in the severe category. As part of the study design, the protocol will enroll patients sequentially. ;

Related Conditions & MeSH terms

• Chronic Granulomatous Disease
• Granuloma
• Granulomatous Disease, Chronic

• NCT number: NCT03910452
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Contact: Elizabeth M Kang, M.D.
• Phone: (301) 402-7567
• Email: ekang@niaid.nih.gov
• Status: Recruiting
• Phase: Early Phase 1
• Start date: October 28, 2019
• Completion date: June 15, 2034