Status:
RECRUITING
TCR Alpha Beta T-cell Depleted Haploidentical HCT in the Treatment of Primary Immunodeficiency and Inherited Metabolic Disorders in Children
Lead Sponsor:
Johns Hopkins All Children's Hospital
Conditions:
Primary Immune Deficiency Disorders
Metabolic Disease
Eligibility:
All Genders
Up to 21 years
Phase:
PHASE2
Brief Summary
This research is being done to learn if a new type of haploidentical transplantation using TCR alpha beta and CD19 depleted stem cell graft from the donor is safe and effective to treat the patient's ...
Eligibility Criteria
Inclusion
- Patient with any form of primary immune deficiency/dysregulatory disorders characterized by aberrant immune function, abnormal hematopoiesis, systemic or organ specific autoimmunity and/or non-malignant lymphoproliferation. This includes, but not limited to:
- I. Disorders of phagocytes: Chronic granulomatous disease, Leukocyte adhesion deficiency, defects of IL-10 pathway, MonoMac syndrome
- II. Defects of cellular and humoral immunity: Severe Combined Immunodeficiency Disorder (infants with classic SCID up to 2 years of age will be excluded due to other open protocol), X-linked hyper-IgM syndrome, DOCK8 deficiency, ZAP70 deficiency, common variable immunodeficiency (CVID), Wiskott-Aldrich syndrome, NEMO deficiency.
- III. Disorder of immune dysregulation: Immunodysregulation polyendocrinopathy enteropathy X-linked (IPEX) syndrome, CTLA4 deficiency, LRBA deficiency, STAT1 GOF, STAT3 GOF, X-linked lymphoproliferative disease etc.
- IV. Other PIDs and immune dysregulatory disorders who can be benefitted by HCT as deemed appropriate by the PI and the treating immunologist.
- Histiocytic disorders including hemophagocytic lymphohistiocytosis (familial HLH (types 1-5), secondary HLH (refractory to therapy or with recurrent episodes of hyper inflammation) and multisystem refractory Langerhans cell histiocytosis.
- Metabolic disorders that could improve or stabilize after stem cell transplantation such as mucopolysaccharidoses, neurodegenerative disorders, osteopetrosis, etc.
- Patient has a suitable genotypic identical match of 5/10. The donor and recipient must be identical, as determined by high resolution typing, at least one allele of each of the following genetic loci: HLA-A, HLA-B, HLA-C, HLA-DRB1 and HLA-DQB1.
- Patients must have adequate organ function measured by:
- Cardiac: asymptomatic or if symptomatic then LVEF at rest must be ≥ 40% or SF ≥ 26%
- Pulmonary: asymptomatic or if symptomatic DLCO ≥ 40% of predicted (corrected for hemoglobin) or pulse oximetry ≥ 92% on room air if the patient is unable to perform pulmonary function testing.
- Renal: Creatinine clearance (CrCl) or glomerular filtration rate (GFR) must be \> 50 mL/min/1.73 m2.
- Hepatic: Serum conjugated (direct) bilirubin \< 2.0 x ULN for age; AST and ALT \< 5.0 x ULN for age.
- Karnofsky or Lansky (age-dependent) performance score ≥ 50
- Signed written informed consent
Exclusion
- Participants who have an HLA-matched sibling who is able and willing to donate bone marrow. Patients with a HLA-matched unrelated donors are not excluded.
- Pregnant or breastfeeding females.
- Patient has HIV or uncontrolled fungal, bacterial or viral infections.
- Patient has received prior solid organ transplant.
- Patient has active GVHD (\> grade II) or chronic extensive GVHD due to a previous allograft at the time of inclusion.
Key Trial Info
Start Date :
July 22 2020
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
June 30 2026
Estimated Enrollment :
17 Patients enrolled
Trial Details
Trial ID
NCT04414046
Start Date
July 22 2020
End Date
June 30 2026
Last Update
June 24 2025
Active Locations (1)
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1
Johns Hopkins All Children's Hospital
St. Petersburg, Florida, United States, 33701