Clinical Trials Logo

Clinical Trial Summary

HLH, HLH-related disorders, Chronic Granulomatous (CGD), HIGM1, Immune dysregulation, polyendocrinopathy, enteropathy, and X-linked inheritance (IPEX) and severe LAD-I represent primary immune disorders that are typically fatal without Hematopoietic Cell Transplant (HCT). However, transplant is often complicated by inflammation, infection and other co-morbidities. In addition, these disorders have been shown to be cured with partial chimerism, making them an ideal target for the use of reduced intensity approaches, where a portion of patients may not achieve full donor chimerism, but instead achieve stable mixed chimerism. Reduced-intensity conditioning strategies have demonstrated improved survival with decreased Treatment Related Mortality (TRM) in institutional series for patients with HLH (Cooper et al., 2006; Marsh et al., 2010; Marsh et al., 2011). However, graft loss and unstable chimerism remain challenges. An institutional case series from Cincinnati Children's Hospital demonstrated full or high-level chimerism and improved durable engraftment using intermediate (Day -14) timing alemtuzumab (Marsh et al., 2013b). This study aims to test the efficacy of the Intermediate RIC strategy in a prospective multi-center study including HLH as well as other primary immunodeficiencies where allogeneic transplant with RIC has been shown to be feasible and stable chimerism is curative.


Clinical Trial Description

The primary goal of this Phase II clinical trial is to determine the one-year overall survival of patients treated for immune deficiencies including HLH, HLH-like disorders, CGD, HIGM1, IPEX syndrome, and severe LAD-I with Matched Related Donor (MRD)/ Matched Unrelated Donor (MUD) bone marrow transplant using a reduced-intensity conditioning strategy including intermediate-timing of alemtuzumab. The donor choice is an unaffected related bone marrow donor who is a 6/6 match at HLA-A, -B (intermediate or higher resolution) and -DRB1 (at high resolution using DNA-based typing) OR a 7/8 or 8/8 match for human leukocyte antigen (HLA)-A, -B, -C and -DRB1 (at high resolution using DNA-based typing), OR an unrelated bone marrow donor who is a 7/8 or 8/8 match at HLA-A, -B, -C and -DRB1 (at high resolution using DNA-based typing). The transplant conditioning regimen will include fludarabine, melphalan, and alemtuzumab starting at Day -14 (Flu/Mel/Alem). Graft Versus Host Disease (GVHD) prophylaxis will consist of cyclosporine and corticosteroids through engraftment. Post-transplant supportive care will include infection surveillance and prophylaxis, and disease-specific supportive care. ;


Study Design


Related Conditions & MeSH terms


NCT number NCT01998633
Study type Interventional
Source Medical College of Wisconsin
Contact
Status Completed
Phase Phase 2
Start date December 2013
Completion date December 2016

See also
  Status Clinical Trial Phase
Withdrawn NCT03278912 - Natural History of Intestinal Inflammation in People With Primary Immune Dysregulations
Recruiting NCT01652092 - Allogeneic Hematopoietic Stem Cell Transplant for Patients With Primary Immune Deficiencies N/A
Completed NCT04136028 - IL-1 Receptor Inhibitor for Granulomatous Complications in Patients With Chronic Granulomatous Disease Early Phase 1
Recruiting NCT05687474 - Baby Detect : Genomic Newborn Screening
Terminated NCT03080480 - Pioglitazone Therapy for Chronic Granulomatous Disease Phase 1/Phase 2
Terminated NCT00394316 - Gene Therapy for Chronic Granulomatous Disease Early Phase 1
Recruiting NCT03910452 - Haploidentical Transplant for People With Chronic Granulomatous Disease (CGD) Using Alemtuzumab, Busulfan and TBI With Post-Transplant Cyclophosphamide Early Phase 1
Terminated NCT02282904 - Haploidentical Transplant for People With Chronic Granulomatous Disease Using Post Transplant Cyclophosphamide Phase 1/Phase 2
Terminated NCT02926963 - Generation of Powerful Biological Tools for Understanding the Pathophysiology of Chronic Granulomatous Disease. N/A
Completed NCT00006417 - Modified Stem Cell Transplantation Procedure for Treating Chronic Granulomatous Disease Phase 2
Completed NCT00368446 - Genetic Disorders of Mucociliary Clearance in Nontuberculous Mycobacterial Lung Disease
Enrolling by invitation NCT03655223 - Early Check: Expanded Screening in Newborns
Recruiting NCT06162936 - Neutrophil Oxidative Burst in Early and Late Onset Pediatric Inflammatory Bowel Disease
Terminated NCT05915897 - Whole Blood Biospecimen Collection for Subjects With Chronic Granulomatous Disease (CGD)
Terminated NCT00325078 - Infliximab to Treat Crohn'S-like Inflammatory Bowel Disease in Chronic Granulomatous Disease Phase 1/Phase 2
Completed NCT00001317 - A Phase IV Study of Recombinant Human Gamma Interferon in Patients With Chronic Granulomatous Diseases of Childhood Phase 4
Completed NCT03548818 - Role of Interferon-gamma 1-b (IFN-γ) on Cells of the Innate Immune System: Functional, Biochemical and Gene Expression Studies in Patients With Chronic Granulomatous Disease
Recruiting NCT01821781 - Immune Disorder HSCT Protocol Phase 2
Completed NCT00578643 - Matched Unrelated or Non-Genotype Identical Related Donor Transplantation For Chronic Granulomatous Disease Phase 2
Terminated NCT00006054 - Allogeneic Bone Marrow Transplantation in Patients With Primary Immunodeficiencies N/A