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

NCT04414046 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: HAP-PIDIRB00249754
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• Incidence of successful donor engraftment

  The incidence of engraftment at day 100 will be described based on donor chimerism in the whole blood and or fractions sorted for T-cell and myeloid subsets. The donor chimerism will be scored as autologous reconstitution (\< 5% donor), mixed chimerism (5-49%=low mixed, 50-95%=high mixed), \> 95%=full donor chimerism.

  Day 100 after transplantation

Secondary Outcomes (11)

• Overall survival and Event-free survival

  Up to 2 years post transplant

• Kinetics of neutrophil engraftment

  Up to 42 days post transplant

• Kinetics of platelet engraftment

  Up to 42 days post transplant

• Transplant-related mortality

  Up to 100 days post transplant

• Acute grade II-IV GvHD

  Up to 2 years post transplant

Study Arms (1)

TCR alpha beta T cell depletion

EXPERIMENTAL

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

Biological: Haploidentical Hematopoietic Cell Transplantation

Interventions

Haploidentical Hematopoietic Cell Transplantation BIOLOGICAL

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

TCR alpha beta T cell depletion

Eligibility Criteria

• Age: Up to 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Johns Hopkins All Children's Hospital: lead

Study Sites (1)

Johns Hopkins All Children's Hospital

St. Petersburg, Florida, 33701, United States

RECRUITING

MeSH Terms

Conditions

Primary Immunodeficiency Diseases; Metabolic Diseases

Condition Hierarchy (Ancestors)

Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Immunologic Deficiency Syndromes; Immune System Diseases; Nutritional and Metabolic Diseases

Study Officials

• Deepak Chellapandian, MD

  Johns Hopkins All Children's Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jade Hanson, MSN

CONTACT

7277676468; jade.hanson@jhmi.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 24, 2020
• First Posted: June 4, 2020
• Study Start: July 22, 2020
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2026
• Last Updated: June 24, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)