NCT02282904

Haploidentical Transplant for People With Chronic Granulomatous Disease Using Post Transplant Cyclophosphamide

Haploidentical Transplant for Patients With Chronic Granulomatous Disease (CGD) Using Post-Transplant Cyclophosphamide

• Status: Terminated
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 7 (actual)
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) · NIH
• Sex: All
• Age: 2 Years – 65 Years
• Healthy volunteers: Not accepted

Summary

Background: \- Chronic Granulomatous Disease (CGD) causes immune system problems. Treatment is usually a bone marrow transplant from a fully matched donor. Researchers want to try using partially matched donors for patients who do not have a fully matched donor available. The researchers will also use the drug cyclophosphamide to try to improve the outcomes when using a partially matched donor. Objective: \- To learn the effectiveness of using cyclophosphamide with a transplant from a partially matched donor in treating CGD. Eligibility: \- Recipients: age 2-65 with CGD with an ongoing infection that has not been cured by standard treatment and no fully matched donor available in an appropriate timeframe. Design: * Recipients will: * be admitted to the hospital 2 weeks before transplant. * be screened with blood and urine tests, breathing and heart health tests, X-rays, and/or magnetic resonance imaging. They may have a bone marrow aspiration and biopsy. * meet with a social worker and dentist. * get chemotherapy, radiation, and other medicines. * get an intravenous (IV) catheter in their chest. * have the transplant. * get more medicines and standard supportive care. * have blood drawn frequently. * have to stay in the Washington, D.C. area for 3 months post-transplant. * be followed closely for the first 6 months, and then less frequently for at least 5 years.

Detailed description

Allogeneic transplant using 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. The use of haploidentical donors has in the past been fraught with a greater rate of complications related to both higher rates of GvHD and delayed immunorecovery. Newer transplant regimens appear to have diminished these risks and improved outcomes. We propose using a subablative conditioning regimen followed by post-transplant cyclophosphamide for patients with CGD who do not have an HLA matched donor but whose circumstances necessitate the use of a potentially curative, albeit high-risk treatment modality.

Conditions

• Chronic Granulomatous Disease

Interventions

Type	Name	Description
DRUG	Sirolimus	For pediatric patients: Begin sirolimus 1 mg/m2 PO q4h for 3 doses, then 1 mg/m2 once a day (QD). For adult patients, begin sirolimus 5 mg PO q4h for 3 doses, then 5 mg once a day (QD). Doses may be adjusted to maintain trough levels between 8-14 ng/ml. Recipients will take sirolimus from Day +5 to at least Day 100 (minimum).
BIOLOGICAL	Donor peripheral blood stem cells.	Infuse donor graft.
DRUG	Cyclophosphamide post transplant	50 mg/kg/d IV infused over 90 minutes. Day +3 and +4
RADIATION	Total body 200cGy	Day -1
DRUG	Cyclophosphamide	14.5 mg/kg IV over one hour Day -6 and -5
DRUG	Fludarabine	30 mg/m2 over 30 minutes Day -6 through Day -2
DRUG	Busulfan	Busulfan 3.2 mg/kg IV once daily over 2-3 hours Day -4,-3,-2

Timeline

• Start date: 2014-10-23
• Primary completion: 2019-04-10
• Completion: 2019-12-10
• First posted: 2014-11-05
• Last updated: 2020-05-12
• Results posted: 2020-05-01

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study