Common Variable Immunodeficiency (CVID)Phase 2CVID/PIRDNCT07284641
Hematopoietic Stem Cell Transplantation (HSCT) for Common Variable Immunodeficiency (CVID) and Other Autoimmune Manifestations of Primary Immune Regulatory Disorders (PIRD)
A Phase 2 study testing Hematopoietic stem cell transplant (HSCT) in people with Common Variable Immunodeficiency (CVID) and Primary Immune Regulatory Disorder, run by Paul Szabolcs at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 5 to 40 years
- Conditions the study is for
- Common Variable Immunodeficiency (CVID), Primary Immune Regulatory Disorder, Immune Dysregulation
- What is being tested?
- Hematopoietic stem cell transplant (HSCT)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteUnited States
- Study dates
- 4 May 2026to 1 Feb 2031
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 5 to 40 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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)
Show all 31Show fewer
- 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
- Mouth and Genital Ulcers with Inflamed Cartilage Syndrome (MAGIC)
- Must have previously failed, due to lack of response or intolerance, mycophenolate mofetil and a B cell-depleting antibody, such as Rituximab
- Glomerular Filtration Rate (GFR) ≥50 mL/min/1.73 m2
- Aspartate Aminotransferase (AST) ≤4x upper limit of normal
- Alanine Aminotransferase (ALT) ≤4x upper limit of normal
- Direct bilirubin ≤ 2.5 mg/dL
- Human Immunodeficiency Virus (HIV) negative by serology and PCR
- Human T-cell Lymphotropic Virus (HTLV) negative by serology
- Cardiac ejection fraction ≥ 40% or shortening fraction ≥26%
- Forced Vital Capacity (FVC) and Forced Expiratory Volume in 1 second (FEV1) ≥40% predicted for age
- Peripheral Capillary Oxygen Saturation (SpO2) of >92% at rest on room air
- Subjects must be a minimum of 8 weeks post-solid organ transplant prior to start of conditioning, if applicable
- Negative pregnancy test for females >10 years old or who have reached menarche, unless surgically sterilized.
- All females of childbearing potential and sexually active males must agree to use a FDA approved method of birth control for up to 12 months after stem cell transplant or for as long as they are taking any medication that may harm a pregnancy, an unborn child or may cause birth defects.
- Subject and/or parent guardian informed of the potential risks of infertility following stem cell transplant and advised to discuss sperm banking or oocyte harvesting.
- Transplant endorsement from clinical immunologist
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
UPMC Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, 15224
Shawna McIntyre, 4126925552, mcintyresm@upmc.edu
A
About this study
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).
Read the 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.
- Conditions
- Common Variable Immunodeficiency (CVID), Primary Immune Regulatory Disorder, Immune Dysregulation, DiGeorge Syndrome, STAT 1 Gain of Function, STAT 3 Gain of Function
- Being tested
- Hematopoietic stem cell transplant (HSCT)
- 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)
- Medical subject headings
- Common Variable Immunodeficiency, DiGeorge Syndrome, Hyper-IgM Immunodeficiency Syndrome, Immune Dysregulation, Polyendocrinopathy, Enteropathy, X-Linked Syndrome, Severe Combined Immunodeficiency, Granulomatous Disease, Chronic, Intestinal Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Biological: Hematopoietic stem cell transplant (HSCT) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Survival post-HSCT
review of the existing medical records to check on the participant's survival status
Measured: 2 years post transplant
Secondary outcomes (6)
engraftment, based upon chimerism data
review of chimerism test results in the existing medical records to check on degree of donor engraftment measured by the percentage of donor-derived blood cells in the HSCT recipient
Measured: 1 month, 2 months, 3 months, 6 months, 12 months, 18 months, 24 months
Assess myeloid, B and T cell chimerism
review test results from medical records to check how donor and recipient cells populate different immune lineages post-transplant
Measured: up to 2 years post translant
Assess Immunoglobulin A (IgA), Immunoglobulin (IgM), and Immunoglobulin E (IgE) reconstitution
review of the existing medical records to check on the participant's humoral immune recovery.
Measured: up to 2 years post transplant
independence of immunoglobulin replacement (IVIG, IgG)
Determine and probability
Measured: 1 and 2 year post transplant
incidence of acute graft versus host disease (GVHD)
grades 3-4
Measured: 6 months post transplant
chronic graft-versus-host-disease
grades 3-4
Measured: 1 year post transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Dec 2025
- Study start4 May 2026
- Primary completion4 May 2030 (estimated)
- Study completion1 Feb 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Common Variable Immunodeficiency (CVID)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- single center, open label, non-randomized
- Masking
- None (open label)
- Enrolment
- 25 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Paul Szabolcs
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Paul Szabolcs, University of Pittsburgh
- Investigators
- Paul Szabolcs, MD, Principal investigator, UPMC Children's Hospital of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07284641
- Sponsor's protocol ID
- STUDY25080140
- Acronym
- CVID/PIRD
- Status last verified
- May 2026
- First submitted
- 8 Dec 2025
- Last updated
- 15 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hematopoietic Stem Cell Transplantation (HSCT) for Common Variable Immunodeficiency (CVID) and Other Autoimmune Manifestations of Primary Immune Regulatory Disorders (PIRD)
- ClinicalTrials.gov ID
- NCT07284641
- Acronym / sponsor ID
- CVID/PIRD / STUDY25080140
- Conditions
- Common Variable Immunodeficiency (CVID), Primary Immune Regulatory Disorder, Immune Dysregulation, DiGeorge Syndrome, STAT 1 Gain of Function, STAT 3 Gain of Function
- Keywords
- HSCT, CVID, PIRD, primary immune regulatory disorder, common variable immunodeficiency, IPEX like syndromes, Immune dysregulation, polyendocrinopathy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 25 participants (estimated)
- Lead sponsor
- Paul SzabolcsUniversity, hospital or other
- Study start
- 4 May 2026 (actual)
- Primary completion
- 4 May 2030 (estimated)
- Study completion
- 1 Feb 2031 (estimated)
- First posted
- 16 Dec 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- single center, open label, non-randomized
| Arm | Type | Receives |
|---|---|---|
| Hematopoietic stem cell transplant (HSCT) | Other | Biological: 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 |
Who may qualify
- Ages
- 5 to 40 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (31 listed)
- 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.
- Must have previously failed, due to lack of response or intolerance, mycophenolate mofetil and a B cell-depleting antibody, such as Rituximab
- Glomerular Filtration Rate (GFR) ≥50 mL/min/1.73 m2
Key exclusion criteria (4 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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. | Biological | Hematopoietic stem cell transplant (HSCT) |
Primary outcome
Survival post-HSCT
Time frame: 2 years post transplant
review of the existing medical records to check on the participant's survival status
6 secondary outcomes
engraftment, based upon chimerism data
Time frame: 1 month, 2 months, 3 months, 6 months, 12 months, 18 months, 24 months
Assess myeloid, B and T cell chimerism
Time frame: up to 2 years post translant
Assess Immunoglobulin A (IgA), Immunoglobulin (IgM), and Immunoglobulin E (IgE) reconstitution
Time frame: up to 2 years post transplant
independence of immunoglobulin replacement (IVIG, IgG)
Time frame: 1 and 2 year post transplant
incidence of acute graft versus host disease (GVHD)
Time frame: 6 months post transplant
chronic graft-versus-host-disease
Time frame: 1 year post transplant
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 May 2026.
- Individual participant dataSharing planned: No
Related trials for Common Variable Immunodeficiency (CVID)
RecruitingObservational study
Immune Regulation in Patients With Common Variable Immunodeficiency and Related Inborn Errors of Immunity (IEI)
XLA, CVID
RecruitingPhase 2
Pilot Trial of Allogeneic Blood or Marrow Transplantation for Primary Immunodeficiencies
Primary T-cell Immunodeficiency Disorders, Common Variable Immunodeficiency
RecruitingPhase 2
Allogeneic Hematopoietic Stem Cell Transplant for Patients With Inborn Errors of Immunity
Lymphoproliferative Disorders, Autoimmune Lymphoproliferative
Enrolling by invitationObservational study
Establishing Fibroblast-Derived Cell Lines From Skin Biopsies of Patients With Immunodeficiency or Immunodysregulation Disorders
Primary Immunodeficiency, DOCK8
RecruitingPhase 2
Study of IgPro20 to Prevent Infection in People With Multiple Myeloma and Hypogammaglobulinemia
Multiple Myeloma, Hypogammaglobulinemia
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Paul Szabolcs, MD principal investigator
UPMC Children's Hospital of Pittsburgh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Hematopoietic stem cell transplant (HSCT) in people with Common Variable Immunodeficiency (CVID) and Primary Immune Regulatory Disorder, run by Paul Szabolcs at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 31 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 15 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Shawna A McIntyre, RN (1-412-692-5552, mcintyresm@upmc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Survival post-HSCT (time frame: 2 years post transplant). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 May 2026.