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

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

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.

Study Overview

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

Detailed Description

Not provided

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• France
  • Île-de-France Region
    • Paris, Île-de-France Region, France, 75015
      • Unité d'Immunologie Hématologie Rhumatologie Pédiatrique (UIHR),

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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	Drug: Human T Lymphoid Progenitor (HTLP) injection; 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)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: URC-CIC Paris Descartes Necker Cochin
• Investigators: Study Director: Isabelle ANDRE, PhD, Institut National de la Santé Et de la Recherche Médicale, France; Principal Investigator: Despina MOSHOUS, MD, PhD, Assistance Publique - Hôpitaux de Paris and Université Paris Descartes

Study record dates

Study Major Dates

• Study Start (Actual): May 13, 2020
• Primary Completion (Actual): September 3, 2023
• Study Completion (Actual): April 24, 2024

Study Registration Dates

• First Submitted: March 15, 2019
• First Submitted That Met QC Criteria: March 15, 2019
• First Posted (Actual): March 19, 2019

Study Record Updates

• Last Update Posted (Actual): May 20, 2026
• Last Update Submitted That Met QC Criteria: May 18, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: hematopoietic stem cell transplantation; SCID; Human T Lymphoid Progenitor
• Additional Relevant MeSH Terms: Metabolic Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; DNA Repair-Deficiency Disorders; Primary Immunodeficiency Diseases; Severe Combined Immunodeficiency; Therapeutics; Drug Administration Routes; Drug Therapy; Injections
• Other Study ID Numbers: P150949J; 2018-001029-14 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No