Condition category
Haematological Disorders
Date applied
03/05/2011
Date assigned
20/05/2011
Last edited
01/02/2016
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Prof Adrian Thrasher

ORCID ID

Contact details

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

Additional identifiers

EudraCT number

ClinicalTrials.gov number

NCT01347242

Protocol/serial number

GTG002.07

Study information

Scientific title

Phase I/II clinical trial of haematopoietic stem cell gene therapy for the Wiskott-Aldrich Syndrome

Acronym

Study hypothesis

Studying 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

Gene Therapy Advisory Committee (GTAC) (UK), 21/12/2009, GTAC 146

Study design

Open-labelled non-randomised single-centre phase I/II cohort study

Primary study design

Interventional

Secondary study design

Non randomised study

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Wiskott-Aldrich Syndrome

Intervention

Ex 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 type

Drug

Phase

Phase I/II

Drug names

Gene therapy

Primary outcome measures

1. 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 measures

1. 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 trial start date

23/02/2010

Overall trial end date

31/12/2013

Reason abandoned

Eligibility

Participant inclusion criteria

1. 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

Participant type

Patient

Age group

Adult

Gender

Male

Target number of participants

5

Participant exclusion criteria

1. 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

Recruitment start date

23/02/2010

Recruitment end date

31/12/2013

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Institute of Child Health
London
WC1N 1EH
United Kingdom

Sponsor information

Organisation

Genethon (France)

Sponsor details

1 bis
rue de l'Internationale
Evry
91000
France

Sponsor type

Industry

Website

http://www.genethon.fr

Funders

Funder type

Industry

Funder name

Genethon (France)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

01/02/2016: No publications found, verifying study status with principal investigator