A Phase 2 Clinical Trial to Evaluate the Efficacy of the Infusion of Autologous CD34+ Cells Transduced With a Lentiviral Vector Carrying the FANCA Gene in Pediatric Subjects With Fanconi Anemia Subtype A

Rocket Pharmaceuticals Inc.2 sites in 1 country5 target enrollmentJuly 15, 2020

ConditionsFanconi Anemia Complementation Group A

InterventionsRP-L102

Overview

Phase: Phase 2
Intervention: RP-L102
Conditions: Fanconi Anemia Complementation Group A
Sponsor: Rocket Pharmaceuticals Inc.
Enrollment: 5
Locations: 2
Primary Endpoint: Bone Marrow (BM) Colony-Forming Cell (CFC) Mitomycin-C (MMC) resistance
Status: Active, not recruiting
Last Updated: 4 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

The objective of this study is to assess the therapeutic efficacy of a hematopoietic cell-based gene therapy for patients with Fanconi anemia, subtype A (FA-A).

Hematopoietic stem cells from mobilized peripheral blood of patients with FA-A will be transduced ex vivo (outside the body) with a lentiviral vector carrying the FANCA gene. After transduction, the corrected stem cells will be infused intravenously back to the patient with the goal of preventing bone marrow failure.

Detailed Description

This is a pediatric open-label Phase II clinical trial to assess the efficacy of a hematopoietic gene therapy consisting of autologous CD34+ enriched cells transduced with a lentiviral vector carrying the FANCA gene in subjects with FA-A. Enriched CD34+ hematopoietic stem cells will be transduced ex vivo with the therapeutic lentiviral vector and infused via intravenous infusion following transduction without any prior conditioning.

Registry

clinicaltrials.gov

Start Date

July 15, 2020

End Date

May 5, 2026

Last Updated

4 months ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Rocket Pharmaceuticals Inc.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Fanconi anemia as diagnosed by chromosomal fragility assay of cultured lymphocytes in the presence of DEB or a similar DNA-crosslinking agent
•Subject of the complementation group FA-A
•Minimum age: 1 year and a minimum weight of 8 kg
•At least 30 CD34+ cells/μL are determined in one bone marrow (BM) aspiration within 3 months prior to CD34+ cell collection OR
•6\. Provide informed consent in accordance with current legislation
•Women of childbearing age must have a negative urine pregnancy test at the baseline visit, and accept the use of an effective contraception method during participation in the trial

Exclusion Criteria

•Subjects with an available and medically eligible HLA-identical sibling donor.
•Evidence of myelodysplastic syndrome or leukemia, or cytogenetic abnormalities other than those reported as variant(s) of normal 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 (≥1 NCI CTCAE grade) in at least one blood lineage over time must be documented to enable eligibility, as should \<5% resistance of bone marrow colony forming cells (CFCs) to 10nM MMC; whenever possible potential mosaicism should also be evaluated by gene sequencing of MMC-resistant CFCs).
•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 criteria of the NCI.
•Pregnant or breastfeeding women.
•Hepatic dysfunction as defined by either:
•Bilirubin \>3.0 × the upper limit of normal (ULN) or
•Alanine aminotransferase (ALT) \> 5.0 × ULN or

Arms & Interventions

RP-L102

RP-L102 is CD34+ enriched cells from subjects with Fanconi anemia subtype A transduced ex vivo with a lentiviral vector carrying the FANCA gene

Intervention: RP-L102

Outcomes

Primary Outcomes

Bone Marrow (BM) Colony-Forming Cell (CFC) Mitomycin-C (MMC) resistance

Time Frame: 21 months

Bone Marrow (BM) colony-forming cell (CFC) mitomycin-C (MMC) resistance ≥20% at 12 months post-infusion with a confirmatory result at 18 or 21 months (MMC at 10 nM concentration)