Hematopoietic Stem Cell Transplantation (HSCT) for Common Variable Immunodeficiency (CVID) and Other Autoimmune Manifestations of Primary Immune Regulatory Disorders (PIRD)
Overview
- Phase
- Phase 2
- Status
- Recruiting
- Sponsor
- Paul Szabolcs
- Enrollment
- 25
- Locations
- 1
- Primary Endpoint
- Survival post-HSCT
Overview
Brief Summary
This is a research protocol that will examine Hematopoietic Stem Cell Transplantation (HSCT) using a reduced conditioning regimen (RIC) with total body Irradiation (TBI) in those diagnosed with Common Variable Immunodeficiency (CVID) and Other Autoimmune Manifestations of Primary Immune Regulatory Disorders (PIRD).
Detailed Description
Hematopoietic stem cell transplant (HSCT) with reduced-intensity conditioning has been demonstrated as the best definitive therapy to correct many of these inheritable immune defects (Common Variable Immunodeficiency (CVID) and Other Autoimmune Manifestations of Primary Immune Regulatory Disorders (PIRD). This is a single center, open label, non-randomized, Phase II study in which subjects receive an allogenic, fully (8 of 8 match) or partially Human Leukocyte Antigen (HLA)-matched (6-7/8 HLA-matched), stem cell transplant utilizing a conditioning regimen of alemtuzumab/Campath, anti-thymocyte globulin/rabbit (ATG), Fludarabine and Melphalan and Total Body Irradiation (TBI). Graft sources include bone marrow or mobilized peripheral blood stem cells from either a related or unrelated donor. After stem cell infusion, subjects are followed for 2 years per standard of care practices.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 5 Years to 40 Years (Child, Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Patient, parent, or legal guardian must have given written informed consent. For pediatric subjects who are developmentally able, assent or affirmation will be obtained.
- •Male or female, 5 through 40 years old, inclusive, at the time of informed consent.
- •Patients must have evidence of common variable immunodeficiency (CVID) or other autoimmune manifestation of a primary immune regulatory disorder (PIRD). Genetic screening is required by a targeting gene panel to determine presence of genetic variations that may lead to inborn errors of immunity.
- •Examples of such diseases include, but are not limited to:
- •Common variable immunodeficiency (CVID)
- •Combined Immunodeficiency (CID)
- •Immune dysregulation polyendocrinopathy enteropathy X-linked (IPEX syndrome), IPEX like syndromes
- •Combined immunodeficiency with defects in T-cell-mediated immunity, including Omenn syndrome and DiGeorge Syndrome
- •Chronic Granulomatous Disease (CGD)
- •Signal Transducer and Activator of Transcription (STAT 1) Gain of Function (STAT1 GOF)
Exclusion Criteria
- •Allergy to Dimethylsulfoxide (DMSO) or any other ingredient used in the manufacturing of the stem cell product
- •Uncontrolled systemic infection, as determined by the appropriate confirmatory testing e.g. blood cultures, Polymerase chain reaction (PCR) testing, etc.
- •Recent recipient of any licensed or investigational live attenuated vaccine(s) within 4 weeks of stem cell transplant
- •Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the subject's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study.
Arms & Interventions
Hematopoietic stem cell transplant (HSCT)
The participant will receive an allogenic, fully (8 of 8 match) or partially HLA-matched (6-7/8 HLA-matched), stem cell transplant utilizing a conditioning regimen of alemtuzumab/Campath, anti-thymocyte globulin/rabbit ATG, Fludarabine and Melphalan and total body irradiation
Intervention: Hematopoietic stem cell transplant (HSCT) (Biological)
Outcomes
Primary Outcomes
Survival post-HSCT
Time Frame: 2 years post transplant
review of the existing medical records to check on the participant's survival status
Secondary Outcomes
- engraftment, based upon chimerism data(1 month, 2 months, 3 months, 6 months, 12 months, 18 months, 24 months)
- Assess myeloid, B and T cell chimerism(up to 2 years post translant)
- independence of immunoglobulin replacement (IVIG, IgG)(1 and 2 year post transplant)
- incidence of acute graft versus host disease (GVHD)(6 months post transplant)
- Assess Immunoglobulin A (IgA), Immunoglobulin (IgM), and Immunoglobulin E (IgE) reconstitution(up to 2 years post transplant)
- chronic graft-versus-host-disease(1 year post transplant)
Investigators
Paul Szabolcs
Professor
University of Pittsburgh