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This Long-Term Follow-Up (LTFU) for Gene Therapy of Leukocyte Adhesion Deficiency-I (LAD-I) is a continuation of a Phase 1/2 clinical study to evaluate the safety and efficacy of the infusion of autologous hematopoietic stem cells transduced with a lentiviral vector encoding the ITGB2 gene
Following the end of participation in Study RP-L201-0318, patients will be offered enrollment into this LTFU protocol. Patients will be followed for up to 15 years following the RP-L201 infusion in the parent study, until the patient dies, withdraws consent, or is lost to follow-up (whichever occurs first).
For all follow-up visits, remote evaluation facilitated by local health care providers (with blood sample shipment to relevant laboratory facilities) is permitted; however, annual visits to the study center are required during initial 3 years post- RP-L201 infusion. Visits where a bone marrow sample is being collected are required to be performed at the study center for the duration of the study. Peripheral Blood samples and bone marrow samples will be archived and tested when clinically or scientifically indicated, as in the event of development of a second malignancy.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Subjects that received RP-L201 on the RP-L201-0318 Parent Study | Subjects that received RP-L201 on the RP-L201-0318 Parent Study and either completed the study or discontinued early. |
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| Measure | Description | Time Frame |
|---|---|---|
| Hematopoietic stem cell transplant (HSCT) free survival | Survival without allogeneic-HSCT. | 15 years |
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of hospitalizations | Incidence of infection-related hospitalizations. | 15 years |
| Incidence of significant infections | Incidence of infections requiring hospitalization or intravenous antimicrobials. |
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Inclusion Criteria:
Exclusion Criteria:
There are no criteria for exclusion in this study.
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Subjects that have been treated with RP-L201 on the RP-L201-0318 study.
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| Name | Affiliation | Role |
|---|---|---|
| Donald Kohn, MD | University of California, Los Angeles | Principal Investigator |
| Claire Booth, MBBS, PhD, MSc | University College London Great Ormond Street Institute of Child Health | Principal Investigator |
| Julian Sevilla, MD, PhD | Hospital Infantil Universitario Niño Jesús | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of California, Los Angeles (UCLA) | Los Angeles | California | 90095-1489 | United States | ||
| Hospital Infantil Universitario Niño Jesús |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40305711 | Derived | Booth C, Sevilla J, Almarza E, Kuo CY, Zubicaray J, Terrazas D, O'Toole G, Chitty-Lopez M, Choi G, Nicoletti E, Long-Boyle J, Fernandes A, Chetty K, De Oliveira S, Banuelos C, Xu-Bayford J, Bastone AL, John-Neek P, Jackson C, Moore TB, Gilmour K, Schambach A, Rothe M, Kasbekar S, Rao GR, Patel K, Shah G, Thrasher AJ, Bueren JA, Schwartz JD, Kohn DB. Lentiviral Gene Therapy for Severe Leukocyte Adhesion Deficiency Type 1. N Engl J Med. 2025 May 1;392(17):1698-1709. doi: 10.1056/NEJMoa2407376. |
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| ID | Term |
|---|---|
| C535887 | Leukocyte adhesion deficiency type 1 |
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Human Tissue (including blood and bone marrow)
| 15 years |
| Resolution of LAD-I-related skin rash | Partial or complete resolution of LAD-I skin rash evident by photographical images. | 15 years |
| Resolution of LAD-I-related periodontal abnormalities | Partial or complete resolution of LAD-I periodontal abnormalities evident by photographical images. | 15 years |
| Event free survival | Survival in the absence of graft failure and graft versus host disease. | 15 years |
| Overall Survival | Survival in the absence of death from any cause | 15 years |
| Long-term genetic correction in peripheral blood mononuclear cells (PBMCs) | Persistence of transgene in PB cells as demonstrated by vector copy number (VCN) of at least 0.1 in PBMCs. | 15 years |
| Long-term genetic correction in PB CD15+ granulocytes | Persistence of transgene in PB cells as demonstrated by VCN of at least 0.1 in PB CD15+ granulocytes. | 15 years |
| Long-term CD18 neutrophil expression by flow cytometry | Persistence of CD18 neutrophil expression defined by PB neutrophil CD18 expression to at least 10% of normal. | 15 Years |
| Long-term CD11 neutrophil expression by flow cytometry | Persistence of CD11 a/b neutrophil co-expression | 15 Years |
| Improvement or resolution of LAD-I related neutrophilia | Improvement of LAD-I related neutrophilia based off neutrophils within age-appropriate normal ranges. | 15 Years |
| Improvement or resolution of LAD-I-related leukocytosis. | Improvement of LAD-I related leukocytosis based off leukocytes within age-appropriate normal ranges. | 15 Years |
| Incidence of Investigational Product (IP) related serious adverse events (SAEs) | Incidence of SAEs related to the IP measured by CTCAE (Common Terminology Criteria for Adverse Events) for V5.0 grading scale. | 15 Years |
| Incidence of hematologic malignancy | Incidence of hematologic malignancy related to prior gene therapy or gene-therapy associated medications. | 15 Years |
| Madrid |
| 28009 |
| Spain |
| University College London Great Ormond Street Institute of Child Health (GOSH) | London | WC1N 1EH | United Kingdom |