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

Assistance Publique - Hôpitaux de Paris4 enrolled

Overview

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.

Not provided

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

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

Interventions

Eligibility

Sex: ALLMin age: 2 YearsMax age: 18 Years

Medical Language ↔ Plain English

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)

Outcomes

Primary Outcomes

Dose limiting toxicity (DLT)

to evaluate the procedure safety

Time frame: 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

Time frame: Month 3

Secondary Outcomes

Time course of reconstitution of the different T cell subpopulations

time necessary to reach a normal number of naïve CD4+ and CD8+ T cells

Time frame: Month 3, month 6, month 12

presence of recent thymic emigrants

To evaluate the active thymopoiesis

Time frame: Month 3, month 6, month 12

T-cell receptor excision circles (TREC ) number in peripheral blood

To evaluate the active thymopoiesis

Time frame: Month 3, month 6, month 12

TCR rearrangements

By NGS analysis

Time frame: 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

Time frame: Month 6, month 12

Immunoglobulin (Ig) levels

Time frame: Month 6, month 12

NK cell numbers

Time frame: Month 6, month 12

Cumulative incidence of infections

Time frame: 12 months post-transplant

Cumulative incidence of acute and chronic episodes of graft versus host disease (GVHD)

Time frame: 24 months post-transplant

Overall survival

Time frame: 2 years post-transplant

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

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes