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

Pediatric Patients Clinical Trial

— HTLP Necker  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03879876
• Other study ID #: P150949J
• Secondary ID: 2018-001029-14
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: May 13, 2020
• Est. completion date: June 3, 2025

Study information

• Verified date: September 2022
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: Marina CAVAZZANA, MD & PhD
• Phone: +33 1 44 49 50 68
• Email: m.cavazzana[@]aphp.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

Not provided

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 12
• Est. completion date: June 3, 2025
• Est. primary completion date: September 3, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 18 Years

Eligibility

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)

Related Conditions & MeSH terms

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

Intervention

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)

Locations

Country	Name	City	State
France	Unité d'Immunologie Hématologie Rhumatologie Pédiatrique (UIHR),	Paris	Ile De France

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose limiting toxicity (DLT)	to evaluate the procedure safety	3 months post-transplant
Primary	reconstitution of the CD3+ TCRaß+ cell compartment	determined by the presence of = 300/µL total, circulating CD3+ TCRaß+ T cells to evaluate the efficacy	Month 3
Secondary	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
Secondary	presence of recent thymic emigrants	To evaluate the active thymopoiesis	Month 3, month 6, month 12
Secondary	T-cell receptor excision circles (TREC ) number in peripheral blood	To evaluate the active thymopoiesis	Month 3, month 6, month 12
Secondary	TCR rearrangements	By NGS analysis	Month 3, month 6, month 12
Secondary	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
Secondary	Immunoglobulin (Ig) levels		Month 6, month 12
Secondary	NK cell numbers		Month 6, month 12
Secondary	Cumulative incidence of infections		12 months post-transplant
Secondary	Cumulative incidence of acute and chronic episodes of graft versus host disease (GVHD)		24 months post-transplant
Secondary	Overall survival		2 years post-transplant