Any Type of Severe Combined Immunodeficiency (SCID), Partial HLA Incompatible Allogeneic Hematopoietic Stem Cell Transplantation (HSCT), Pediatric Patients
Conditions
Keywords
SCID, hematopoietic stem cell transplantation, Human T Lymphoid Progenitor
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
Interventions
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)
Sponsors
Assistance Publique - Hôpitaux de Paris
URC-CIC Paris Descartes Necker Cochin
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 18 Years
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose limiting toxicity (DLT) | 3 months post-transplant | to evaluate the procedure safety |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| presence of recent thymic emigrants | Month 3, month 6, month 12 | To evaluate the active thymopoiesis |
| T-cell receptor excision circles (TREC ) number in peripheral blood | Month 3, month 6, month 12 | To evaluate the active thymopoiesis |
| TCR rearrangements | Month 3, month 6, month 12 | By NGS analysis |
| 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 |
| 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 | — |
Countries
France
Contacts
STUDY_DIRECTORIsabelle ANDRE, PhD
Institut National de la Santé Et de la Recherche Médicale, France
PRINCIPAL_INVESTIGATORDespina MOSHOUS, MD, PhD
Assistance Publique - Hôpitaux de Paris and Université Paris Descartes
Outcome results
None listed