Hematopoietic Stem Cell Transplantation (HSCT) for Common Variable Immunodeficiency (CVID) and Other Autoimmune Manifestations of Primary Immune Regulatory Disorders (PIRD)

NCT07284641 | Recruiting Phase 2 FDA Drug

• 1 other identifier: STUDY25080140
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

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).

Conditions

Primary Immune Regulatory Disorder; DiGeorge Syndrome; STAT 3 Gain of Function; CD40 Ligand Deficiency; GATA2 Associated Immunodeficiency; Omenn Syndrome; Hypomorphic RAG1 Deficiency; Hypomorphic RAG2 Deficiency; Chronic Granulomatous Disease; Common Variable Immunodeficiency (CVID); Immune Dysregulation; STAT 1 Gain of Function; Mendelian Susceptibility to Mycobacterial Disease; CD40 Deficiency; Immune Dysregulation Polyendocrinopathy Enteropathy X-Linked Syndrome

Keywords

HSCT; CVID; PIRD; primary immune regulatory disorder; common variable immunodeficiency; IPEX like syndromes; Immune dysregulation; polyendocrinopathy; enteropathy; X-linked (IPEX syndrome); DiGeorge Syndrome; Combined Immunodeficiency; Chronic Granulomatous Disease; STAT 1 Gain of Function; STAT 3 Gain of Function; Hypomorphic RAG 1 and RAG 2; CD40 or CD40L deficiency; Mendelian Susceptibility to Mycobacterial Disease; GATA2 Associated Immunodeficiency; Inflamed Cartilage Syndrome (MAGIC)

Outcome Measures

Primary Outcomes (1)

• Survival post-HSCT

  review of the existing medical records to check on the participant's survival status

  2 years post transplant

Secondary Outcomes (6)

• 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

• Assess Immunoglobulin A (IgA), Immunoglobulin (IgM), and Immunoglobulin E (IgE) reconstitution

  up to 2 years post transplant

• independence of immunoglobulin replacement (IVIG, IgG)

  1 and 2 year post transplant

• incidence of acute graft versus host disease (GVHD)

  6 months post transplant

Study Arms (1)

Hematopoietic stem cell transplant (HSCT)

OTHER

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

Biological: Hematopoietic stem cell transplant (HSCT)

Interventions

Hematopoietic stem cell transplant (HSCT) BIOLOGICAL

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.

Hematopoietic stem cell transplant (HSCT)

Eligibility Criteria

• Age: 5 Years - 40 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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)
• Signal Transducer and Activator of Transcription (STAT 3) Gain of Function (STAT3 GOF)
• Hypomorphic Recombination-Activating Genes (RAG) 1 and RAG 2
• CD40 or CD40L deficiency
• Mendelian Susceptibility to Mycobacterial Disease
• GATA-binding factor 2 (GATA2) Associated Immunodeficiency

You may not qualify if:

• 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.

Sponsors & Collaborators

• Paul Szabolcs: lead

Study Sites (1)

UPMC Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15224, United States

RECRUITING

MeSH Terms

Conditions

Common Variable Immunodeficiency; DiGeorge Syndrome; Hyper-IgM Immunodeficiency Syndrome; Immune Dysregulation, Polyendocrinopathy, Enteropathy, X-Linked Syndrome; Severe Combined Immunodeficiency; Granulomatous Disease, Chronic; Intestinal Diseases

Interventions

Stem Cell Transplantation

Condition Hierarchy (Ancestors)

Immunologic Deficiency Syndromes; Immune System Diseases; 22q11 Deletion Syndrome; Craniofacial Abnormalities; Musculoskeletal Abnormalities; Musculoskeletal Diseases; Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Lymphatic Abnormalities; Lymphatic Diseases; Hemic and Lymphatic Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Chromosome Disorders; Genetic Diseases, Inborn; Hypoparathyroidism; Parathyroid Diseases; Endocrine System Diseases; Dysgammaglobulinemia; Blood Protein Disorders; Hematologic Diseases; Primary Immunodeficiency Diseases; Infant, Newborn, Diseases; DNA Repair-Deficiency Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Phagocyte Bactericidal Dysfunction; Leukocyte Disorders; Genetic Diseases, X-Linked; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Gastrointestinal Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative

Study Officials

• Paul Szabolcs, MD

  UPMC Children's Hospital of Pittsburgh

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Shawna A McIntyre, RN

CONTACT

1-412-692-5552; mcintyresm@upmc.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Model Details: single center, open label, non-randomized

Study Record Dates

• First Submitted: December 8, 2025
• First Posted: December 16, 2025
• Study Start (Estimated): May 15, 2026
• Primary Completion (Estimated): February 1, 2030
• Study Completion (Estimated): February 1, 2031
• Last Updated: May 6, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)