Safety and Efficacy Study of Human T Lymphoid Progenitor (HTLP) Injection After Partially HLA Compatible Allogeneic Hematopoietic Stem Cell Transplantation in SCID Patients

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and the efficacy of Human T Lymphoid Progenitor (HTLP) injection to accelerate immune reconstitution after partially HLA compatible allogeneic hematopoietic stem cell transplantation in SCID patients.

Detailed Description
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Not provided

Official Title
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A Phase I/II Study Evaluating the Safety and the Efficacy of Human T Lymphoid Progenitor (HTLP) Injection to Accelerate Immune Reconstitution After Partially HLA Compatible Allogeneic Hematopoietic Stem Cell Transplantation in SCID Patients

Conditions
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Pediatric Patients, Any Type of Severe Combined Immunodeficiency (SCID), Partial HLA Incompatible Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)

Intervention / Treatment
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* Drug: Human T Lymphoid Progenitor (HTLP) injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pediatric patients affected by any type of SCID confirmed by clinical, immunological and/or molecular diagnosis and eligible for an allogeneic HSCT Absence of a matched sibling donor or a matched unrelated donor (MUD) 10/10 Clinical conditions incompatible with the search of a MUD Written, informed consent of parents/ legal representative (child) Age ≤ 2 years at the time of screening No prior therapy with allogeneic stem cell transplantation No treatment with another investigational drug within one month before inclusion Patient affiliated to social security Exclusion Criteria: Presence of an HLA genoidentical donor Absence of written parental consent Treatment with another investigational drug within one month before inclusion Positive for HIV infection by genome PCR Contra-indication to allogeneic transplantation or conditioning therapy (except SCID patients with DNA repair deficiency)

Ages Eligible for Study
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Minimum Age: 2 Years
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: Human T Lymphoid Progenitor (HTLP) injection<br>Human T Lymphoid Progenitor cells (HTLPs) obtained after a brief period of ex vivo culture in the presence of the fusion protein DL-4, Retronectin® and a combination of cytokines | Drug: Human T Lymphoid Progenitor (HTLP) injection<br>* Injection of progenitors derived from HTLP culture at Day 8-Day 12 after partially HLA compatible allogeneic hematopoietic stem cell transplantation in SCID patients (Day7 of culture)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose limiting toxicity (DLT) | to evaluate the procedure safety | 3 months post-transplant | 
| reconstitution of the CD3+ TCRαβ+ cell compartment | determined by the presence of ≥ 300/µL total, circulating CD3+ TCRαβ+ T cells to evaluate the efficacy | Month 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time course of reconstitution of the different T cell subpopulations | time necessary to reach a normal number of naïve CD4+ and CD8+ T cells | Month 3, month 6, month 12 | 
| presence of recent thymic emigrants | To evaluate the active thymopoiesis | Month 3, month 6, month 12 | 
| T-cell receptor excision circles (TREC ) number in peripheral blood | To evaluate the active thymopoiesis | Month 3, month 6, month 12 | 
| TCR rearrangements | By NGS analysis | Month 3, month 6, month 12 | 
| B-cell reconstitution | number and phenotype for naïve IgD+CD27-, marginal zone IgD+CD27+, switched memory IgD-CD27+, and IgD-CD27- cells | Month 6, month 12 | 
| Immunoglobulin (Ig) levels |  | Month 6, month 12 | 
| NK cell numbers |  | Month 6, month 12 | 
| Cumulative incidence of infections |  | 12 months post-transplant | 
| Cumulative incidence of acute and chronic episodes of graft versus host disease (GVHD) |  | 24 months post-transplant | 
| Overall survival |  | 2 years post-transplant | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SCID, hematopoietic stem cell transplantation, Human T Lymphoid Progenitor