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

Phase 1

Terminated

Interventions: Drug: Sirolimus
Biological: Donor peripheral blood stem cells.
Drug: Cyclophosphamide post transplant
Radiation: Total body 200cGy
Drug: Cyclophosphamide
Drug: Fludarabine
Drug: Busulfan

Brief 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.

Recruitment & Eligibility

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Arm && Interventions

Group	Intervention	Description
CGD Recipient	Total body 200cGy	CGD patients that will undergo haplo transplantation with post-transplant cyclophosphamide as described
CGD Recipient	Donor peripheral blood stem cells.	CGD patients that will undergo haplo transplantation with post-transplant cyclophosphamide as described
CGD Recipient	Cyclophosphamide post transplant	CGD patients that will undergo haplo transplantation with post-transplant cyclophosphamide as described
CGD Recipient	Sirolimus	CGD patients that will undergo haplo transplantation with post-transplant cyclophosphamide as described
CGD Recipient	Cyclophosphamide	CGD patients that will undergo haplo transplantation with post-transplant cyclophosphamide as described
CGD Recipient	Fludarabine	CGD patients that will undergo haplo transplantation with post-transplant cyclophosphamide as described
CGD Recipient	Busulfan	CGD patients that will undergo haplo transplantation with post-transplant cyclophosphamide as described

Primary Outcome Measures

Name	Time	Method
To Determine the Efficacy of This Allogeneic Transplant Approach in Reconstituting Normal Hematopoiesis and Reversing the Clinical Phenotype of CGD	5 years	Patient will have donor chimerism of greater than 20% and resolution of infection or autoimmunity at end of follow up

Secondary Outcome Measures

Name	Time	Method
To Determine the Safety of This Allogeneic HSCT Approach in Patients With CGD Including Transplant Related Toxicity, the Incidence of Acute and Chronic Graft-versus-host Disease, Immune Reconstitution, Overalland Disease-free Survival.	1 year post transplant	1. Stable chimerism as indicated by 30-50% myeloid engraftment and 50% lymphoid engraftment as assessed by 1 year post transplant. 2. Immune reconstitution levels with DHR as a marker of normal neutrophil function by 1 year post transplant. 3. GvHD grades of less than 3.