Reduced-intensity hematopoietic stem cell transplant for CVID and other primary immune regulatory disorders

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This single-center, open-label Phase II study gives allogeneic hematopoietic stem cell transplants to patients with common variable immunodeficiency or other primary immune regulatory disorders using a reduced-intensity conditioning regimen. Conditioning combines alemtuzumab (Campath) or rabbit ATG, fludarabine, melphalan and low-dose total body irradiation, and grafts come from 8/8 or 6–7/8 HLA-matched related or unrelated donors using bone marrow or mobilized peripheral blood. The protocol is non-randomized and subjects are followed for two years after infusion according to standard clinical care. The study targets patients with genetic or clinical evidence of PIRD/CVID and uses a targeted gene panel as part of screening.

Why it matters

Who can join: the full rules

Inclusion Criteria:

1. Patient, parent, or legal guardian must have given written informed consent. For pediatric subjects who are developmentally able, assent or affirmation will be obtained.
2. Male or female, 5 through 40 years old, inclusive, at the time of informed consent.
3. 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
   * Mouth and Genital Ulcers with Inflamed Cartilage Syndrome (MAGIC)
4. Must have previously failed, due to lack of response or intolerance, mycophenolate mofetil and a B cell-depleting antibody, such as Rituximab
5. Glomerular Filtration Rate (GFR) ≥50 mL/min/1.73 m2
6. Aspartate Aminotransferase (AST) ≤4x upper limit of normal
7. Alanine Aminotransferase (ALT) ≤4x upper limit of normal
8. Direct bilirubin ≤ 2.5 mg/dL
9. Human Immunodeficiency Virus (HIV) negative by serology and PCR
10. Human T-cell Lymphotropic Virus (HTLV) negative by serology
11. Cardiac ejection fraction ≥ 40% or shortening fraction ≥26%
12. Forced Vital Capacity (FVC) and Forced Expiratory Volume in 1 second (FEV1) ≥40% predicted for age
13. Peripheral Capillary Oxygen Saturation (SpO2) of \>92% at rest on room air
14. Subjects must be a minimum of 8 weeks post-solid organ transplant prior to start of conditioning, if applicable
15. Negative pregnancy test for females \>10 years old or who have reached menarche, unless surgically sterilized.
16. 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.
17. 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.
18. Transplant endorsement from clinical immunologist

Exclusion Criteria:

1. Allergy to Dimethylsulfoxide (DMSO) or any other ingredient used in the manufacturing of the stem cell product
2. Uncontrolled systemic infection, as determined by the appropriate confirmatory testing e.g. blood cultures, Polymerase chain reaction (PCR) testing, etc.
3. Recent recipient of any licensed or investigational live attenuated vaccine(s) within 4 weeks of stem cell transplant
4. 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.

Where it's running

• UPMC Children's Hospital of Pittsburgh
  Pittsburgh, Pennsylvania, United States Recruiting

Study contacts

• Principal investigator: Paul Szabolcs, MD — UPMC Children's Hospital of Pittsburgh
• Study coordinator: Shawna A McIntyre, RN
• Email: mcintyresm@upmc.edu
• Phone: 1-412-692-5552

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

• Understanding congenital bone marrow failure and related disorders through a national network

  This project tests whether people with rare inherited bone marrow failure syndromes or related conditions really have the underlying genetic causes, by collecting data and samples across multiple centers.

  Recruiting at 4 sites Istituto Giannina Gaslini · Avellino and 3 other locations · NCT07877727

• Toxin exposure and immune factors in B-cell non-Hodgkin lymphoma

  This study tests how toxin exposure, genetics, and immune issues relate to B-cell non-Hodgkin lymphoma in active-duty service members and other Military Health System beneficiaries.

  Recruiting Henry M. Jackson Foundation for the Advancement of Military Medicine · Bethesda, Maryland and 2 other locations · NCT07652580

• Immune cells in lung disease and how they could guide immunotherapy

  This project sees if immune cell profiling from blood can explain why people with lung cancer, sarcoidosis, or COPD respond differently to immunotherapy or develop chronic lung inflammation.

  Recruiting Université Catholique de Louvain · Brussels · NCT07384897

• Using CD45RA Depleted Stem Cells to Prevent Infections After Transplant

  This study is testing whether using special stem cells can help patients with high-risk leukemia recover their immune system faster and prevent infections after a stem cell transplant.

  Recruiting Phase 1/2 Children's Hospital of Philadelphia · Philadelphia, Pennsylvania · NCT06839456

• Using metformin to improve immune function in people with a history of injection drug use

  This study is testing if the diabetes drug metformin can help improve the immune system and reduce inflammation in people aged 18-64 who have a history of using injection drugs.

  Recruiting Phase 4 University of Alabama at Birmingham · Birmingham, Alabama · NCT06829238

• Treatment of inflammation before stem cell transplant for immune disorders

  This study is testing if a new treatment can help reduce inflammation in people with immune disorders before they get a stem cell transplant to improve the chances of a successful procedure.

  Recruiting at 6 sites Phase 2 Columbia University · San Francisco, California and 12 other locations · NCT05787574

How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.