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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)

Primary Purpose

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

Status
Recruiting
Phase
Phase 1
Locations
France
Study Type
Interventional
Intervention
Human T Lymphoid Progenitor (HTLP) injection
Sponsored by
Assistance Publique - Hôpitaux de Paris
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pediatric Patients focused on measuring SCID, hematopoietic stem cell transplantation, Human T Lymphoid Progenitor

Eligibility Criteria

2 Years - 18 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • Unité d'Immunologie Hématologie Rhumatologie Pédiatrique (UIHR),Recruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Human T Lymphoid Progenitor (HTLP) injection

Arm Description

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

Outcomes

Primary Outcome Measures

Dose limiting toxicity (DLT)
to evaluate the procedure safety
reconstitution of the CD3+ TCRαβ+ cell compartment
determined by the presence of ≥ 300/µL total, circulating CD3+ TCRαβ+ T cells to evaluate the efficacy

Secondary Outcome Measures

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

Full Information

First Posted
March 15, 2019
Last Updated
September 26, 2022
Sponsor
Assistance Publique - Hôpitaux de Paris
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1. Study Identification

Unique Protocol Identification Number
NCT03879876
Brief Title
Safety and Efficacy Study of Human T Lymphoid Progenitor (HTLP) Injection After Partially HLA Compatible Allogeneic Hematopoietic Stem Cell Transplantation in SCID Patients
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2022
Overall Recruitment Status
Recruiting
Study Start Date
May 13, 2020 (Actual)
Primary Completion Date
September 3, 2023 (Anticipated)
Study Completion Date
June 3, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Assistance Publique - Hôpitaux de Paris

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. 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.
Detailed Description
Not provided

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pediatric Patients, Any Type of Severe Combined Immunodeficiency (SCID), Partial HLA Incompatible Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)
Keywords
SCID, hematopoietic stem cell transplantation, Human T Lymphoid Progenitor

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Human T Lymphoid Progenitor (HTLP) injection
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Human T Lymphoid Progenitor (HTLP) injection
Intervention Description
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)
Primary Outcome Measure Information:
Title
Dose limiting toxicity (DLT)
Description
to evaluate the procedure safety
Time Frame
3 months post-transplant
Title
reconstitution of the CD3+ TCRαβ+ cell compartment
Description
determined by the presence of ≥ 300/µL total, circulating CD3+ TCRαβ+ T cells to evaluate the efficacy
Time Frame
Month 3
Secondary Outcome Measure Information:
Title
Time course of reconstitution of the different T cell subpopulations
Description
time necessary to reach a normal number of naïve CD4+ and CD8+ T cells
Time Frame
Month 3, month 6, month 12
Title
presence of recent thymic emigrants
Description
To evaluate the active thymopoiesis
Time Frame
Month 3, month 6, month 12
Title
T-cell receptor excision circles (TREC ) number in peripheral blood
Description
To evaluate the active thymopoiesis
Time Frame
Month 3, month 6, month 12
Title
TCR rearrangements
Description
By NGS analysis
Time Frame
Month 3, month 6, month 12
Title
B-cell reconstitution
Description
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
Title
Immunoglobulin (Ig) levels
Time Frame
Month 6, month 12
Title
NK cell numbers
Time Frame
Month 6, month 12
Title
Cumulative incidence of infections
Time Frame
12 months post-transplant
Title
Cumulative incidence of acute and chronic episodes of graft versus host disease (GVHD)
Time Frame
24 months post-transplant
Title
Overall survival
Time Frame
2 years post-transplant

10. Eligibility

Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Marina CAVAZZANA, MD & PhD
Phone
+33 1 44 49 50 68
Email
m.cavazzana@aphp.fr
First Name & Middle Initial & Last Name or Official Title & Degree
Jinmi BAEK
Phone
+33 1 42 19 28 49
Email
jinmi.beak@aphp.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Isabelle ANDRE, PhD
Organizational Affiliation
Institut National de la Santé Et de la Recherche Médicale, France
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Despina MOSHOUS, MD, PhD
Organizational Affiliation
Assistance Publique - Hôpitaux de Paris and Université Paris Descartes
Official's Role
Principal Investigator
Facility Information:
Facility Name
Unité d'Immunologie Hématologie Rhumatologie Pédiatrique (UIHR),
City
Paris
State/Province
Ile De France
ZIP/Postal Code
75015
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Marina CAVAZZANA, MD, PhD
Phone
33 1 44 49 50 68
Email
m.cavazzana@aphp.fr

12. IPD Sharing Statement

Plan to Share IPD
No

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

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