Clinical characteristics, management, and hematopoietic cell transplantation of patients with TLR8 gain-of-function.
Danielle E Arnold, Saara Kaviany, Jahnavi Aluri...
https://pubmed.ncbi.nlm.nih.gov/41370196Actively Recruiting
Phase 2
Age: 4Years - 69Years
All Genders
ID04339777
A Phase II Study of Allogeneic Hematopoietic Stem Cell Transplant for Patients With Inborn Errors of Immunity
Led by National Cancer Institute (NCI) · Updated on 2026-05-04
66
Participants Needed
1
Research Sites
60 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
Researchers are evaluating allogeneic hematopoietic stem cell transplantation (HSCT) as a potential treatment for people aged 4 to 69 years with inborn errors of immunity (IEI), also known as primary immunodeficiency diseases (PID) or Primary Immune Regulatory Disorders (PIRD). These conditions cause significant health problems due to immune system defects, often leading to recurrent infections or immune dysregulation. The study aims to assess whether HSCT can restore normal immune function and reverse disease symptoms by establishing sustained donor blood cell engraftment. The study offers different transplant conditioning regimens based on patient needs, including low, intermediate, and high intensity options. These regimens involve drugs like fludarabine and busulfan, dosed according to pharmacokinetic monitoring, and may include alemtuzumab for immune dysregulation or total body irradiation for certain donor matches. After conditioning, participants receive stem cells from matched or haploidentical donors through transplantation. Post-transplant, patients receive medications such as cyclophosphamide, mycophenolate mofetil, and tacrolimus to prevent graft-versus-host disease. Treatment schedules and drug doses vary by transplant intensity and donor matching. Participants undergo thorough screening including medical history, physical exams, blood and urine tests, heart tests, and imaging scans before transplantation. They are hospitalized for at least four weeks during the transplant and receive ongoing monitoring through blood, urine, bone marrow, and stool sample collections. Follow-up visits occur at days 30, 60, 100, 180, 360, 24 months post-transplant, and annually for about five years to assess immune recovery, disease reversal, transplant complications, and survival outcomes. The study closely tracks safety and effectiveness measures related to donor cell engraftment and immune function restoration.
CONDITIONS
Brief Title
Allogeneic Hematopoietic Stem Cell Transplant for Patients With Inborn Errors of Immunity
Who Can Participate
Age: 4Years - 69Years
All Genders
Eligibility Criteria
You may qualify if you...
- Age between 4 and 69 years with weight at least 12 kilograms
- Mutation in a known monogenic immune deficiency gene confirmed by certified lab, with failed or no standard treatment
- Or clinical history showing immune defects such as recurrent infections, immune dysregulation, atopy, hemophagocytic lymphohistiocytosis, hypogammaglobulinemia, impaired vaccine response, or virally-driven malignancy
- Availability of a matched or haploidentical related or unrelated donor
- Karnofsky or Lansky performance status of 40% or higher
- Adequate heart function with ejection fraction over 40%
- Kidney function within defined creatinine levels and clearance
- Liver function with bilirubin under 2.5 mg/dl and liver enzymes within limits
- Lung function with FEV1 and DLCO over 30%; children unable to test DLCO eligible if no breathing issues
- Ability to understand and sign informed consent; guardians consent for minors
- Agreement to use effective contraception during and for one year after transplant
- Willingness to stay near the hospital for at least 100 days after transplant or have an adult caregiver if outpatient
You will not qualify if you...
- Receiving other investigational treatments except virus-specific therapies before transplant
- Known brain metastases
- HIV positive status
- Allergic reactions to study drugs such as steroids, cyclophosphamide, busulfan, tacrolimus, sirolimus, mycophenolate mofetil, G-CSF, alemtuzumab
- Active psychiatric disorder that risks compliance or informed consent
- Pregnant or breastfeeding women
- Uncontrolled illnesses like symptomatic heart failure, unstable angina, cardiac arrhythmia, or psychiatric/social issues limiting study compliance
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
1
2
3
Your Study Journey
Screening
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Conditioning
Duration - Approximately 2 weeks before transplant
Participants receive a transplant conditioning regimen of varying intensity including fludarabine and busulfan doses, with some also receiving alemtuzumab and total body irradiation depending on donor matching and immune dysregulation.
Daily treatments on days -14 to -1 depending on regimen
Allogeneic Hematopoietic Stem Cell Transplant (HSCT)
Duration - 1 day
Participants undergo stem cell transplant on day 0 following conditioning.
1 visit (in-person) for transplant procedure
Post-Transplant Care
Duration - Approximately 6 months
Participants receive graft-versus-host disease prophylaxis including cyclophosphamide, mycophenolate mofetil, and tacrolimus, and are monitored for transplant recovery and complications.
Frequent visits from day +3 to about day +180 with medication administration and monitoring
Long-term Monitoring
Duration - Up to 5 years post transplant
Participants are followed to assess sustained donor engraftment, reversal of immune abnormalities, and overall survival up to 5 years post transplant.
Regular follow-up visits over several years for health assessments
Trial Site Locations
Total: 1 location
1
National Institutes of Health Clinical Center
Bethesda, Maryland, United States, 20892
Actively Recruiting
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Research Team
S
Shannon L Knight, R.N.
S
Sung-Yun Pai, M.D.
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NON_RANDOMIZED
Model
PARALLEL
Primary Purpose
TREATMENT
Number of Arms
2
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