D82.0
Conditions
Interventions
Group 1: transfusion of gene-corrected hematopoietic stem/progenitor cells
Sponsors
Direktor der Kinderklinik und Kinderpoliklinik
im Dr. von Haunerschen Kinderspital
Eligibility
Sex/Gender
Male
Age
12 Months to No maximum
Inclusion criteria
Inclusion criteria: 1. Classic Wiskott-Aldrich-Syndrome verified by molecular analysis of the WASP-gene. Patients with residual protein expression can be enroled, if they experienced at least one episode of life-threatening complications (severe infection or bleeding) 2. Age > 12 months 3. No signs of a malignant disease (exclusion of lymphoma by ultrasonic abdomen examination, chest x-ray, bone marrow cytological analysis) 4. informed consent or informed assent by patients or legal representative 5. Sufficient number of vital CD34+ cells (>1 x 10e5 CD34+ cells/kg bodyweight) isolated from bone marrow or mobilised apherese preparation
Exclusion criteria
Exclusion criteria: 1.WASP mutations in the context of congenital neutropenia (GBD-mutations) or congenital thrombocytopenia (XLT) 2.Positive screening result for WASP proviral sequences by PCR analysis, or evidence of replication-competent retroviruses by detection of GALV-hull protein sequences by PCR or a positive S+L- assay 3.Patients who are participating in other clinical trials with investigational drugs 4.Patients or legal representatives respectively with a medical or psychiatric condition that compromises the ability to participate in the study or to give informed consent
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Feasibility of ex vivo gene marking of autologous hematopoietic cells which contribute to short- and long-term hematopoiesis after partially myeloablative conditioning 2. Safety of retroviral gene transfer into hematopoietic stem cells, in particular with regards to the absence of replication-competent retroviral particles and analysis of insertional mutagenesis after transfusion of genetically modified stem cells 3. Efficacy of WASP reconstitution in the hematopoietic system, as demonstrated by reconstitution of immunologic effector cell function, normalization of blood paramaters and decrease of infectious complications | — |
Secondary
| Measure | Time frame |
|---|---|
| Determination of frequency and functionality of the gene therapy vector encoding WASP by molecular insertion site analysis and demonstration of genetic correction using cell biological assays in peripheral blood and bone marrow leukocytes 2. Determination of the engraftment potential and efficacy of differentiation into multiple hematopoietic cell lineages 3. Determination of persistence of molecular cell clones in diverse cell lineages of the hematopoietic system 4. Monitoring of hematopoiesis with an emphasis on the potential contribution of genetically marked and reconstituted cells to the development of myelodysplastic syndrome or malignant transformation 5. Determination of the expression level of WASP in hematopoietic cells and correction of cellular phenotype | — |
Countries
Australia, Germany, Hungary, Lebanon, Russia, Syria, United States
Contacts
Public ContactChristoph Klein
Direktor der Kinderklinik und Kinderpoliklinik im Dr. von Haunerschen Kinderspital
Outcome results
None listed