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

Official title

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

Overview

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.

Interventions

• Biological Haploidentical Hematopoietic Cell Transplantation
  TCR alpha beta T-cell and CD19 B-cell depleted haploidentical transplantation

Primary outcome measures

• Incidence of successful donor engraftment [Time frame: Day 100 after transplantation]

Secondary outcome measures (11)

• Overall survival and Event-free survival [Time frame: Up to 2 years post transplant]
• Kinetics of neutrophil engraftment [Time frame: Up to 42 days post transplant]
• Kinetics of platelet engraftment [Time frame: Up to 42 days post transplant]
• Transplant-related mortality [Time frame: Up to 100 days post transplant]
• Acute grade II-IV GvHD [Time frame: Up to 2 years post transplant]
• Chronic GvHD [Time frame: Up to 2 years post transplant]
• Primary graft failure [Time frame: Up to 2 years post transplant]
• Secondary graft failure [Time frame: Up to 2 years post transplant]
• Transplant-related complications [Time frame: Up to 2 years post transplant]
• Transplant-related infections [Time frame: Up to 2 years post transplant]
• Cellular and Immunological reconstitution by laboratory evaluations [Time frame: Up to 2 years post transplant]

Eligibility criteria

Inclusion criteria

• 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.

Inclusion criteria

• 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 criteria

• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• Johns Hopkins All Children's Hospital — St. Petersburg

Identifiers

NCT: NCT04414046 · HAP-PID · IRB00249754

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗