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

• Sponsor: Assistance Publique - Hôpitaux de Paris (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT03879876
• Collaborator: (none)
• Enrollment: 12
• Location: 1
• Arm: 1
• Anticipated Duration (Months): 60.7
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Pediatric Patients; Any Type of Severe Combined Immunodeficiency (SCID); Partial HLA Incompatible Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)	Drug: Human T Lymphoid Progenitor (HTLP) injection	Phase 1/Phase 2

Detailed Description

Not provided

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 12 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: May 13, 2020
• Anticipated Primary Completion Date: Sep 3, 2023
• Anticipated Study Completion Date: Jun 3, 2025

Arms and Interventions

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)

Outcome Measures

Primary Outcome Measures

1. Dose limiting toxicity (DLT) [3 months post-transplant]

   to evaluate the procedure safety

2. 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

Secondary Outcome Measures

1. 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

2. presence of recent thymic emigrants [Month 3, month 6, month 12]

   To evaluate the active thymopoiesis

3. T-cell receptor excision circles (TREC ) number in peripheral blood [Month 3, month 6, month 12]

   To evaluate the active thymopoiesis

4. TCR rearrangements [Month 3, month 6, month 12]

   By NGS analysis

5. 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

6. Immunoglobulin (Ig) levels [Month 6, month 12]

7. NK cell numbers [Month 6, month 12]

8. Cumulative incidence of infections [12 months post-transplant]

9. Cumulative incidence of acute and chronic episodes of graft versus host disease (GVHD) [24 months post-transplant]

10. Overall survival [2 years post-transplant]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 2 Years to 18 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Unité d'Immunologie Hématologie Rhumatologie Pédiatrique (UIHR),	Paris	Ile De France	France	75015

Sponsors and Collaborators

• Assistance Publique - Hôpitaux de Paris

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 Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Assistance Publique - Hôpitaux de Paris
• ClinicalTrials.gov Identifier: NCT03879876
• Other Study ID Numbers: P150949J; 2018-001029-14
• First Posted: Mar 19, 2019
• Last Update Posted: Apr 15, 2021
• Last Verified: Apr 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Assistance Publique - Hôpitaux de Paris: SCID; hematopoietic stem cell transplantation; Human T Lymphoid Progenitor
• Additional relevant MeSH terms: Severe Combined Immunodeficiency

Study Results

No Results Posted as of Apr 15, 2021