Condition category
Haematological Disorders
Date applied
03/05/2011
Date assigned
20/05/2011
Last edited
20/05/2011
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 Alain Fischer

ORCID ID

Contact details

Unité d'Immunologie et d'Hématologie Pédiatriques
Hôpital Necker-Enfants Malades
149 rue de Sèvres
Paris
75015
France

Additional identifiers

EudraCT number

ClinicalTrials.gov number

NCT01347346

Protocol/serial number

GTG003.08

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

Committee to Protect People (Comité de Protection des Personnes) - Ile de France 2 approved on 11th August 2009, (ref : 2009-04-01)

Study design

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

Primary study design

Interventional

Secondary study design

Non randomised controlled trial

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 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 1 x 106CD34+ cells per kg; retrospective undetectable (replication-competent lentiviruses)RCL; and cell viability equal to or greater than 70%, in accordance with the GMO 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 (as assessed by increased blood platelet counts, expected to rise above 50,000/mm3 and platelets size restoration)

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 (as assessed by clinical monitoring)

Overall trial start date

16/05/2011

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. Unless desease severity indicates that one cannot wait for 3 months (score 5; refractory thrombocytopenia with platelets < 5000 with bleeding or severe autoimmunity)
5. Lack of HLA-genotypically identical bone marrow after 3 month search
6. Lack of a 10/10 or 9/10 antigen HLA-matched unrelated donor after 3 month search
7. Lack of a HLA-matched cord blood after 3 month search
8. Parental, guardian, patient signed informed consent/assessment
9. Willing to return for follow-up during the 2 year study and lifelong for off study review
10. Only for patients who have received previous allogenic haematopoietic stem cell transplant
10.1. Failed allogenic haematopoietic stem cell transplant
10.2. Contraindication to repeat allogenic transplantation

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 or 9/10 antigen HLA-matched unrelated donor or with HLA-matched cord blood
3. Contraindication to leukapheresis
3.1. Anaemia (Hb < 8g/dl)
3.2. Severe vascularitis
3.3. Refractory thrompopenia
3.3.1. Contraindication to bone marrow harvest
3.3.2. Contraindication to administration of conditioning medication
4. Human immunodeficiency virus (HIV) seropositive patient

Recruitment start date

16/05/2011

Recruitment end date

31/12/2013

Locations

Countries of recruitment

France

Trial participating centre

Unité d'Immunologie et d'Hématologie Pédiatriques
Paris
75015
France

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