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

Phase 1

Recruiting

• Conditions: Any Type of Severe Combined Immunodeficiency (SCID); Pediatric Patients; Partial HLA Incompatible Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)
• Interventions: Drug: Human T Lymphoid Progenitor (HTLP) injection

• Registration Number: NCT03879876
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Brief Summary

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

Not provided

Study Timeline

• Study First Submitted: 2019-03-15
• Study First Submitted QC: 2019-03-15
• Study First Posted: 2019-03-19
• Study Start: 2020-05-13
• Status Verified: 2022-09
• Last Update Submitted: 2022-09-26
• Last Update Posted: 2022-09-27
• Primary Completion: 2023-09-03
• Study Completion: 2025-06-03

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 12

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Human T Lymphoid Progenitor (HTLP) injection	Human T Lymphoid Progenitor (HTLP) injection	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

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Unité d'Immunologie Hématologie Rhumatologie Pédiatrique (UIHR),; 🇫🇷 Paris, Ile De France, France