ISRCTN ISRCTN46087965
DOI https://doi.org/10.1186/ISRCTN46087965
ClinicalTrials.gov number NCT01347242
Secondary identifying numbers GTG002.07
Submission date
03/05/2011
Registration date
20/05/2011
Last edited
16/03/2018
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Haematological Disorders
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Prof Adrian Thrasher
Scientific

Molecular Immunology Unit
Institute of Child Health
30 Guildford Street
London
WC1N 1EH
United Kingdom

Study information

Study designOpen-labelled non-randomised single-centre phase I/II cohort study
Primary study designInterventional
Secondary study designNon randomised study
Study setting(s)Hospital
Study typeTreatment
Participant information sheet Not available in web format, please use the contact details to request a patient information sheet
Scientific titlePhase I/II clinical trial of haematopoietic stem cell gene therapy for the Wiskott-Aldrich Syndrome
Study objectivesStudying the safety and efficacy of an ex vivo gene therapy using a lentiviral vector containing the human Wiskott-Aldrich Syndrome protein gene in patients with WAS
Ethics approval(s)Gene Therapy Advisory Committee (GTAC) (UK), 21/12/2009, GTAC 146
Health condition(s) or problem(s) studiedWiskott-Aldrich Syndrome
InterventionEx vivo gene therapy using patient's autologous CD34+ cells transduced with a lentiviral vector containing the human WASP gene.

Patients undergo either a bone marrow harvest or a leukapheresis. They then receive a conditioning myeloablative regimen while CD34+ cells are selected in their bone marrow and transduced with the lentiviral vector (3 days). Patients then receive their transduced CD34+ cells (as in autologous bone marrow transplantation).

There are no real doses, simply quantity of CD34+ cells transduced will depend on the amount of bone marrow harvest and quality of transduction. This is part of the parameters that are being assessed in the trial.

Duration of the study follow-up is 2 years.
Intervention typeDrug
Pharmaceutical study type(s)
PhasePhase I/II
Drug / device / biological / vaccine name(s)
Primary outcome measure1. Safety of conditioning regimen (haematopoietic recovery within 6 weeks as assessed by absolute neutrophil count (ANC) above 0.5 x 109 /l )
2. Safety of the transduction procedure [as assessed by availability of greater than 0.5 x 106 cells per kg after transduction; undetectable replication-competent lentiviruses (RCL) (determined retrospectively); and cell viability after transduction equal to or greater than 50%, in accordance with the final product release criteria]
3. Engraftment of genetically corrected haematopoietic progenitors and/or differentiated cells in peripheral blood and/or in bone marrow (as assessed by evidence of vector sequences or transgene expression in the cells)
4. Reconstitution of cell mediated and humoral immunity (as assessed by evidence of changes in T cell function and circulating immunoglobulin levels)
5. Correction of microthrombocytopenia (if not previously splenectomised, and as assessed by increased blood platelet counts, expected to rise above 50,000/mm3)
Secondary outcome measures1. Reduction in frequency of infections (evaluated from 2nd year after treatment by clinical history, complete physical examinations, haematological and microbiological tests)
2. Resolution/reduction of autoimmunity (a decrease from baseline observations assessed by clinical examination)
3. Improvement in eczema (a decrease from baseline observations assessed by clinical examination)
4. Reduction in bruising and bleeding episodes when present (as assessed by clinical monitoring)
Overall study start date23/02/2010
Completion date31/12/2013

Eligibility

Participant type(s)Patient
Age groupAdult
SexMale
Target number of participants5
Key inclusion criteria1. Males of all ages
2. Severe WAS (clinical score 3 – 5) or absence of WAS protein in peripheral blood mononuclear cells determined by Western blotting and flow cytometry
3. Molecular confirmation by WAS gene DNA sequencing
4. Lack of HLA-genotypically identical bone marrow or of a 10/10 antigen HLA-matched unrelated donor or cord blood after 3 month search
5. Parental, guardian, patient signed informed consent/assessment
6. Willing to return for follow-up during the 2 year study and the 3 year long-term off study review
7. Only for patients who have received previous allogenic haematopoietic stem cell transplant:
7.1. Failed allogenic haematopoietic stem cell transplant
7.2. Contraindication to repeat allogeneic transplantation for example severe graft versus host disease
Key exclusion criteria1. Patient with HLA-genotypically identical bone marrow
2. Patient with 10/10 antigen HLA-matched unrelated donor or cord blood
3. Contraindication to leukapheresis
3.1. Anaemia (Hb < 8g/dl)
3.2. Cardiovascular instability
3.3. Severe coagulopathy
3.3.1. Contraindication to bone marrow harvest
3.3.2. Contraindication to administration of conditioning medication
3. Human immunodeficiency virus (HIV) positive patient
Date of first enrolment23/02/2010
Date of final enrolment31/12/2013

Locations

Countries of recruitment

  • England
  • United Kingdom

Study participating centre

Institute of Child Health
London
WC1N 1EH
United Kingdom

Sponsor information

Genethon (France)
Industry

1 bis, rue de l'Internationale
Evry
91000
France

Website http://www.genethon.fr
ROR logo "ROR" https://ror.org/03fj96t64

Funders

Funder type

Industry

Genethon (France)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
Publication and dissemination planNot provided at time of registration
IPD sharing plan

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Results article results 14/09/2017 Yes No

Editorial Notes

16/03/2018: Publication reference added.
01/02/2016: No publications found, verifying study status with principal investigator