TCR Alpha Beta T-cell Depleted Haploidentical HCT in the Treatment of Primary Immunodeficiency and Inherited Metabolic Disorders in Children

NCT ID: NCT04414046

Last Updated: 2025-06-24

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 17 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-07-22
• Study Completion Date: 2026-06-30

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 underlying condition. This study will use stem cells obtained via peripheral blood or bone marrow from parent or other half-matched family member donor. These will be processed through a special device called CliniMACS, which is considered investigational.

Conditions

Primary Immune Deficiency Disorders; Metabolic Disease

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

TCR alpha beta T cell depletion

The leukapheresis product will undergo TCR alpha beta negative selection following a standardized protocol

Group Type: EXPERIMENTAL

Haploidentical Hematopoietic Cell Transplantation

Intervention Type: BIOLOGICAL

TCR alpha beta T-cell and CD19 B-cell depleted haploidentical transplantation

Interventions

Haploidentical Hematopoietic Cell Transplantation

TCR alpha beta T-cell and CD19 B-cell depleted haploidentical transplantation

Intervention Type: BIOLOGICAL

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.

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.

• Maximum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Johns Hopkins All Children's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Deepak Chellapandian, MD

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins All Children's Hospital

Locations

Johns Hopkins All Children's Hospital

St. Petersburg, Florida, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Jade Hanson, MSN

Role: CONTACT

jade.hanson@jhmi.edu

7277676468

Facility Contacts

Ian Snyder

Role: primary

isnyder5@jhmi.edu

Other Identifiers

IRB00249754

Identifier Type: OTHER

Identifier Source: secondary_id

HAP-PID

Identifier Type: -

Identifier Source: org_study_id