Haploidentical stem cell transplantation for treating immune and metabolic disorders in children

Study of TCR Alpha Beta T-Cell and CD19 B-Cell Depletion for Hematopoietic Cell Transplantation From Haploidentical Donors in the Treatment of Primary Immunodeficiency and Inherited Metabolic Disorders in Children

This study is testing a new way to use stem cells from family members to treat children with immune and metabolic disorders to see if it helps them feel better.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 17 (estimated)
• Ages: N/A to 21 Years
• Sex: All
• Sponsor: Johns Hopkins All Children's Hospital (Academic / other)
• Locations: 1 site (St. Petersburg, Florida)
• Trial ID: NCT04414046 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the safety and effectiveness of a new haploidentical transplantation method using TCR alpha beta and CD19 depleted stem cell grafts from half-matched family donors. The study aims to treat children with primary immune deficiency disorders and inherited metabolic diseases by utilizing stem cells obtained from peripheral blood or bone marrow. The grafts will be processed using an investigational device called CliniMACS to enhance the transplantation process. The trial is designed to assess the outcomes of this innovative approach in a pediatric population.

Who should consider this trial

Good fit: Ideal candidates for this study are children diagnosed with various forms of primary immune deficiency or inherited metabolic disorders.

Not a fit: Patients with classic Severe Combined Immunodeficiency Disorder (SCID) who are under 2 years of age may not benefit from this study due to exclusion criteria.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for children suffering from severe immune deficiencies and metabolic disorders.

How similar studies have performed: Other studies have explored haploidentical transplantation approaches, showing promising results, but this specific method is considered novel.

Eligibility criteria

Inclusion Criteria:

1. 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.
2. 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.
3. Metabolic disorders that could improve or stabilize after stem cell transplantation such as mucopolysaccharidoses, neurodegenerative disorders, osteopetrosis, etc.

Inclusion Criteria:

1. 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.
2. Patients must have adequate organ function measured by:

   1. Cardiac: asymptomatic or if symptomatic then LVEF at rest must be ≥ 40% or SF ≥ 26%
   2. 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.
   3. Renal: Creatinine clearance (CrCl) or glomerular filtration rate (GFR) must be \> 50 mL/min/1.73 m2.
   4. Hepatic: Serum conjugated (direct) bilirubin \< 2.0 x ULN for age; AST and ALT \< 5.0 x ULN for age.
   5. Karnofsky or Lansky (age-dependent) performance score ≥ 50
3. Signed written informed consent

Exclusion Criteria:

1. 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.
2. Pregnant or breastfeeding females.
3. Patient has HIV or uncontrolled fungal, bacterial or viral infections.
4. Patient has received prior solid organ transplant.
5. Patient has active GVHD (\> grade II) or chronic extensive GVHD due to a previous allograft at the time of inclusion.

Where this trial is running

St. Petersburg, Florida

• Johns Hopkins All Children's Hospital — St. Petersburg, Florida, United States (Recruiting)

Study contacts

• Principal investigator: Deepak Chellapandian, MD — Johns Hopkins All Children's Hospital
• Study coordinator: Jade Hanson, MSN

Conditions Primary Immune Deficiency Disorders; Metabolic Disease