TCR Alpha/Beta Depletion for HSCT From Haploidentical and Unrelated Donors in the Treatment of PID

Study Overview
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Brief Summary
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Treatment Study to assess of safety and efficiency of T cells receptor (TCR) alfa beta depleted graft for hematopoietic stem cell transplantation (HSCT) from haploidentical and unrelated donors in patients with primary immunodeficiency diseases

Detailed Description
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Infections, graft versus host diseases (GVHD) and associated morbidity and mortality remains significant problems after unrelated and haploidentical hematopoietic stem sell transplantation (HSCT) in patients with primary immunodeficiency diseases (PID). In this study the hypothesis is that the transplantation of TCR alfa beta depleted peripheral blood stem cells (PBSC) would offers advantages over the use of positively selected CD34+ stem cells in haploidentical HSCT and non-manipulated graft in unrelated HSCT. The purpose of this study is to evaluate the safety and efficiency of the selective infusion of TCR alfa beta T cell depleted graft in pediatric patients with PID receiving HSCT from haploidentical and unrelated donors.

Official Title
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Phase II/III Study of Allogeneic Hematopoietic Stem Cell Transplantation From Unrelated and Haploidentical Donors After TCR Alfa Beta Negative Selection in Pediatric Patients With Primary Immunodeficiency Diseases

Conditions
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Primary Immune Deficiency Disorder, Hematopoietic Stem Cell Transplantation

Intervention / Treatment
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* Other: Biological: TCR alfa beta T cell depletion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients aged ≥ 1 months and < 19 years Patients diagnosed with Primary Immunodeficiency Diseases eligible for an allogeneic transplantation and lacking a related HLA-matched donor Lansky/Karnofsky score > 40, WHO > 4 Signed written informed consent Exclusion Criteria: Dysfunction of liver (ALT/AST > 5 times normal value, or bilirubin > 3 times normal value), or of renal function (creatinine clearance < 30 ml / min) Severe cardiovascular disease (arrhythmias requiring chronic treatment, congestive heart failure or left ventricular ejection fraction <40%) Serious concurrent uncontrolled medical disorder Pregnant or breast feeding female patient Lack of parents' informed consent.

Ages Eligible for Study
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Minimum Age: 1 Month
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TCR alfa beta depletion<br>TCR alfa beta depleted graft, infusion. The leukapheresis product will undergo TCR alfa beta depletion following the standardized protocol. | Other: Biological: TCR alfa beta T cell depletion<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | The probability of overall survival estimated by the Kaplan-Meier method at 1 year after HSCT | 1 year after HSCT | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Transplant Related Mortality (TRM) | transplant-related mortality estimated with cumulative incidence curve, considering relapse as a competitive risk | 24 months after transplantation | 
| Acute Graft Versus Host Diseases (аGVHD) | incidence of aGVHD II-IV stage estimated with cumulative incidence curve, considering graft rejection and death as competitive risks | 12 months after transplantation | 
| Chronic Graft Versus Host Diseases (cGVHD) | incidence of cGVHD estimated with cumulative incidence curve, considering graft rejection and death as competitive risks | 1 year after HSCT | 
| Cellular Immunological Reconstitution | Number of participants, who reached immune recovery - CD19+ lymphocytes subsets | 2 years after HSCT | 
| Percentage of Patients With Full Donor Chimerism | Percentage of patients with full (more than 90%) donor chimerism among survivals | last follow-up | 
| Viral Infections After Transplant | number of patients with CMV reactivation (detection of any grade of CMV viremia after HSCT) | 12 months after transplantation |