A phase I/II clinical trial of hematopoietic stem cell gene therapy for Wiskott-Aldrich Syndrome

UMIN ID: UMIN000030806

Registered date:15/01/2018

Basic Information

• Recruitment status: Complete: follow-up continuing
• Health condition(s) or Problem(s) studied: Wiskott-Aldrich syndrome
• Date of first enrollment: 2018/01/17
• Target sample size: 3
• Countries of recruitment: Japan
• Study type: Interventional
• Intervention(s): WASP cDNA-transduced autologous hematopoietic stem cells are administered to patients affected by WAS after the administration of rituximab and preconditioning chemotherapy including Fludarabine and Busulfan. 1. Rituximab (day-22) 375 mg/m2 2. Preconditioning chemotherapy Fludarabine 30mg/m2 x 2 (day-3, day-2) Busulfan cumulative target AUC 48000 ng/mL*h (day-3 to -1, every 6 hours) 3. Infusion of WASP cDNA-transduced CD34 positive HSC 5 x 10^6/kg (at least 3 x 10^6/kg)

Outcome(s)

• Primary Outcome: Safety of reduced conditioning regimen and LV gene transfer into HSC -Hematological reconstitution -Regimen related non-hematological toxicity -Short-term safety and tolerability of LV-transduced cell infusion -The absence of replication competent LV and abnormal clonal proliferation Efficacy of gene therapy -Overall survival -Sustained engraftment of genetically corrected hematopoietic stem cells -Improvement in immune function -Improvement in platelet count

Key inclusion & exclusion criteria

• Age minimum: Not applicable
• Age maximum: Not applicable
• Gender: Male
• Exclude criteria: Patients who meet any of the following criteria will be excluded. 1. Patients positive for HIV infection 2. Patients affected by neoplasia 3. Patients with cytogenetic alterations typical of MDS/AML 4. Patients with end-organ function or any other severe disease, which, in the judgement of the investigator, would make the patients inappropriate for entry into this study 5. Patients who underwent an allogeneic hematopoietic stem cell transplantation in the previous 6 months 6. Patients who underwent an allogeneic hematopoietic stem cell transplantation with evidence of residual donor cells 7. Patients who have the possibility of severe allergic reactions, to rituximab and the products derived from cow, pig, sheep and mouse. 8. Patients who do not agree with a contraception during the trial. 9. Patients who are considered inappropriate, in the judgement of the investigator, due to any other reasons.

Related Information

• Primary Sponsor: National Center for Child Heath and Development
• Source(s) of Monetary Support: Japan Agency for Medical Research and Development