A Phase I Clinical Trial to Evaluate the Safety of the Infusion of Autologous CD34+ Cells Transduced With a Lentiviral Vector Carrying the FANCA Gene in Pediatric Subjects With Fanconi Anemia Subtype A
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Fanconi Anemia Complementation Group A
- Sponsor
- Rocket Pharmaceuticals Inc.
- Enrollment
- 2
- Locations
- 1
- Primary Endpoint
- Number of participants with treatment-related adverse events as assessed by CTCAE v.5.0
- Last Updated
- 5 years ago
Overview
Brief Summary
The objective of this study is to assess the therapeutic safety and preliminary efficacy of a hematopoietic cell-based gene therapy consisting of autologous CD34+ enriched cells transduced with a lentiviral vector carrying the FANCA gene in subjects with Fanconi anemia subtype A (FA-A).
Detailed Description
This is a pediatric open-label Phase 1 clinical trial and will include a safety evaluation and preliminary assessment of the efficacy of hematopoietic gene therapy consisting of autologous CD34+ enriched cells transduced with a lentiviral vector carrying the FANCA gene in subjects with FA-A. CD34+ cells will be transduced ex vivo with the therapeutic lentiviral vector and infused following transduction, without any prior conditioning. After transduction, product quality control evaluations will be carried out in aliquots of the transduced population. Investigational product will be infused via intravenous infusion with no upper or lower limit; a dose of ≥5 x 105 CD34+ cells/kg body weight will be considered optimal. The active agent is a self-inactivating lentiviral vector carrying the therapeutic FANCA gene and the therapeutic product is subject's autologous HSCs that have been transduced with the lentiviral vector. The vector contains the functional FANCA gene.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Fanconi anemia, as diagnosed by chromosomal fragility assay of cultured T-lymphocytes in the presence of DEB or a similar DNA-crosslinking agent.
- •Subjects of Fanconi Anemia complementation group A.
- •Minimum age: 1 year and a minimum of 8 kg.
- •Maximum age: 12 years.
- •At least one of the following hematologic parameters below lower limits of normal:
- •Hemoglobin
- •Absolute neutrophils
- •Platelets
- •At least 30 CD34+ cells/μL are determined in one BM aspiration within 3 months prior to initiation of CD34+ cell collection.
- •If the number of C34+ cells/ μL in BM is in the range of 10-29, PB parameters should meet two of the three following criteria:
Exclusion Criteria
- •Subjects with an available and medically eligible human leukocyte antigen (HLA)-identical sibling donor.
- •Evidence of myelodysplastic syndrome or leukemia, or cytogenetic abnormalities predictive of these conditions in BM aspirate analysis. This assessment should be made by valid studies conducted within the 3 months before the subject commences the stem cell mobilization/collection procedures of the clinical trial.
- •Subjects with somatic mosaicism associated with stable or improved counts in all PB cell lineages. (If T-lymphocyte chromosomal fragility analysis indicates potential mosaicism, a medically significant decrease in at least one blood lineage over time must be documented to enable eligibility).
- •Lansky performance status ≤60%.
- •Any concomitant disease or condition that, in the opinion of the Principal Investigator, renders the subject unfit to participate in the study.
- •Pre-existing sensory or motor impairment ≥grade 2 according to the NCI CTCAE v5.0 criteria.
- •Pregnant or breastfeeding women.
- •Hepatic dysfunction as defined by either:
- •Bilirubin \>3.0 × upper limit of normal (ULN) or
- •Alanine aminotransferase (ALT) \> 5.0 × ULN or
Outcomes
Primary Outcomes
Number of participants with treatment-related adverse events as assessed by CTCAE v.5.0
Time Frame: 3 years
Evaluation of safety associated with treatment with RP-L102
Secondary Outcomes
- Phenotypic correction of hematopoietic cells in bone marrow after infusion of RP-L102(3 years)
- Phenotypic correction of T-lymphocytes in peripheral blood after infusion of RP-L102(3 years)
- Prevention or rescue of bone marrow failure after infusion of RP-L102(3 years)
- Engraftment of gene-corrected hematopoietic cells after infusion of RP-L102(3 years)