LV Gene Therapy for Fanconi Anaemia
Research type
Research Study
Full title
Phase I/II open label, single centre clinical trial to assess the safety and efficacy of autologous CD34+ cells transduced with lentiviral vector for patients with Fanconi anaemia subtype A
IRAS ID
199930
Contact name
Claire Booth
Contact email
Sponsor organisation
Great Ormond Street Hospital for Children NHS foundation Trust
Eudract number
2011-006197-88
Duration of Study in the UK
5 years, 0 months, 1 days
Research summary
Fanconi anaemia is a rare inherited blood disorder, with an average survival of around 24 years. FA is principally characterised by failure of the bone marrow and an increased predisposition to cancer. At birth, a patient's blood cell count is generally normal, but after 5 to 10 years the bone marrow usually fails, with blood cancer developing by an average age of 7 years.
Currently, there are no medications specifically available for treatment of FA. Allogeneic haematopoietic stem cell transplantation (HSCT), which replaces the patient’s bone marrow with that of a healthy donor, is the only treatment that definitively restores the normal function of the bone marrow. HSCT is the first choice of treatment for patients with signs of bone marrow failure and a fully-matched related donor. However, patients without a fully-matched related donor have much worse overall outcomes from HSCT.
We wish to investigate whether patients with FA subtype A without a fully-matched related donor may benefit from gene therapy. We propose to perform a phase I/II clinical trial to evaluate the safety and efficacy (effect) of gene therapy for FA patients subtype A using a lentivirus delivery system containing the FANCA gene. Five 5 eligible FA subtype A patients will undergo mobilisation and harvest of their haematopoietic stem precursor cells (HPSCs). In the laboratory the disabled lentivirus will be used to insert a normal human FANCA gene into the patient’s harvested HPSCs. The genetically corrected stem cells will then be reinfused into the patient. If, after treating the 1st two patients, there is no evidence of the survival of genetically corrected cells, patients will receive chemotherapy conditioning prior to cell infusion, in order to enhance grafting. Patients will be followed up for 2 years. In this trial, we will determine whether gene therapy for FA subtype A using a lentiviral vector is safe, feasible and effective.REC name
London - West London & GTAC Research Ethics Committee
REC reference
17/LO/1069
Date of REC Opinion
30 Oct 2017
REC opinion
Further Information Favourable Opinion