Chronic Granulomatous Disease Transplant Clinical Trial
Official title:
High Dose Peripheral Blood Stem Cell Transplantation With Post Transplant Cyclophosphamide for Patients With Chronic Granulomatous Disease
Chronic granulomatous disease (CGD) affects white blood cell function. Currently, the only curative treatment is bone marrow transplant to replace the abnormal stem cells with new ones (donor cells) capable of making a normal immune system. Transplant problems include graft versus host disease (GvHD) and graft rejection. With GvHD, donor cells attack the recipient s normal tissue. Researchers want to use preparation drugs and a high cell dose to increase graft success. They want to use 2 immunosuppressive drugs (cyclophosphamide and sirolimus) to lessen the risk of GvHD.
Study Description: Alemtuzumab, targeted busulfan, and TBI, with a 10/10 related or MUD donor graft or a 9/10 single HLA mismatch graft followed by post-transplant cyclophosphamide. Primary Objectives: To determine engraftment rates with the use of high cell doses, without increasing the risk of GvHD by using post-transplant cyclophosphamide and sirolimus in conjunction with a busulfan based conditioning regimen. We will compare the incidence of graft rejection/failure and GvHD to the incidence obtained from Protocol 07-I-0075. Secondary Objectives: To measure the engraftment rate and the engraftment kinetics using such a regimen. To assess the level and kinetics of immune reconstitution (via chimerism) when using post- transplant cyclophosphamide. To further elucidate the factors involved in the development of GvHD and graft rejection/failure. To evaluate the risk of viral infections in the setting of Alemtuzumab (Campath-1H) and post-transplant cyclophosphamide. Primary Endpoint: Reduced incidence of graft failure or rejection (as defined by >20% engraftment by oxidase- positive neutrophils in at least 95% of participants by Day 100, 6 months, and 1 year post BMT) will be assessed as event-free survival (EFS). Graft failure will result in disease recurrence. This will be assessed in a composite form along with GvHD (see Biostatistical Considerations section 17). Secondary Endpoints: Same or reduced rate of grade 3-4 aGvHD of <20% . Establish stable mixed chimerism. Improve rapidity of immune reconstitution. Overall survival. Tertiary Endpoints: Evaluation of inflammatory markers as risk factors for engraftment syndrome ;