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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)

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ClinicalTrials.gov Identifier: NCT03879876
Recruitment Status : Not yet recruiting
First Posted : March 19, 2019
Last Update Posted : March 29, 2019
Sponsor:
Information provided by (Responsible Party):
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.

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

Detailed Description:
Not provided

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 12 participants
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
Estimated Study Start Date : April 2019
Estimated Primary Completion Date : June 2022
Estimated Study Completion Date : April 2024


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
Genetic: 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)




Primary Outcome Measures :
  1. Dose limiting toxicity (DLT) [ Time Frame: 3 months post-transplant ]
    to evaluate the procedure safety

  2. reconstitution of the CD3+ TCRαβ+ cell compartment [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Month 3, month 6, month 12 ]
    To evaluate the active thymopoiesis

  3. T-cell receptor excision circles (TREC ) number in peripheral blood [ Time Frame: Month 3, month 6, month 12 ]
    To evaluate the active thymopoiesis

  4. TCR rearrangements [ Time Frame: Month 3, month 6, month 12 ]
    By NGS analysis

  5. B-cell reconstitution [ Time Frame: 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 [ Time Frame: Month 6, month 12 ]
  7. NK cell numbers [ Time Frame: Month 6, month 12 ]
  8. Cumulative incidence of infections [ Time Frame: 12 months post-transplant ]
  9. Cumulative incidence of acute and chronic episodes of graft versus host disease (GVHD) [ Time Frame: 24 months post-transplant ]
  10. Overall survival [ Time Frame: 2 years post-transplant ]


Information from the National Library of Medicine

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Ages Eligible for Study:   2 Years to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03879876


Contacts
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Contact: Marina CAVAZZANA, MD & PhD +33 1 44 49 50 68 m.cavazzana@aphp.fr
Contact: Valérie JOLAINE, manager +33 1 42 19 28 79 valerie.jolaine@aphp.fr

Locations
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France
Unité d'Immunologie Hématologie Rhumatologie Pédiatrique (UIHR), Not yet recruiting
Paris, Ile De France, France, 75015
Contact: Marina CAVAZZANA, MD, PhD    33 1 44 49 50 68    m.cavazzana@aphp.fr   
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
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Study Director: Isabelle André-Schmutz, 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

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Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT03879876     History of Changes
Other Study ID Numbers: P150949J
2018-001029-14 ( EudraCT Number )
First Posted: March 19, 2019    Key Record Dates
Last Update Posted: March 29, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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:
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Immunologic Deficiency Syndromes
Severe Combined Immunodeficiency
Immune System Diseases
Infant, Newborn, Diseases
DNA Repair-Deficiency Disorders
Metabolic Diseases