UMIN-CTR Clinical Trial

Basic information
Public title	A phase I/II clinical trial of hematopoietic stem cell gene therapy for Wiskott-Aldrich Syndrome
Acronym	Hematopoietic stem cell gene therapy for Wiskott-Aldrich Syndrome
Scientific Title	A phase I/II clinical trial of hematopoietic stem cell gene therapy for Wiskott-Aldrich Syndrome
Scientific Title:Acronym	Hematopoietic stem cell gene therapy for Wiskott-Aldrich Syndrome
Region	Japan

Condition
Condition	Wiskott-Aldrich syndrome
Classification by specialty	Medicine in general Hematology and clinical oncology Pediatrics
Classification by malignancy	Others
Genomic information	YES

Objectives
Narrative objectives1	The objective of the present gene therapy clinical trial is to evaluate the safety of the transduced stem cells infusion in patients affected by WAS after a reduced-intensity conditioning regimen and its efficacy in improving the patients' immune-function and thrombocytopenia.
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1	Exploratory
Trial characteristics_2	Explanatory
Developmental phase	Phase I,II

Assessment
Primary outcomes	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 secondary outcomes

Base
Study type	Interventional

Study design
Basic design	Single arm
Randomization	Non-randomized
Randomization unit
Blinding	Open -no one is blinded
Control	Uncontrolled
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment

Intervention
No. of arms	1
Purpose of intervention	Treatment
Type of intervention	Medicine Gene
Interventions/Control_1	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)
Interventions/Control_2
Interventions/Control_3
Interventions/Control_4
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10

Eligibility
Age-lower limit	Not applicable
Age-upper limit	Not applicable
Gender	Male
Key inclusion criteria	Patients who meet all of the following criteria will be included. 1. Diagnosis of WAS determined by genetic mutation and at least one of the following: -Severe WASP mutation -Absent WASP expression -Severe clinical score (Zhu clinical score greater than or equal to 3) 2. Donor for HSCT -Patients with age less than 5: Negative search for related and unrelated HLA-identical donor -Patients with age greater than or equal to 5: Negative search for related HLA-identical donor
Key exclusion 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.
Target sample size	3

Research contact person
Name of lead principal investigator	1st name Middle name Last name MASAFUMI ONODERA
Organization	National Center for Child Heath and Development
Division name	Division of Immunology
Zip code
Address	2-10-1 Okura, Setagaya-ku, Tokyo, Japan
TEL	03-5494-7295
Email	onodera-m@ncchd.go.jp

Public contact
Name of contact person	1st name Middle name Last name TORU UCHIYAMA
Organization	National Center for Child Heath and Development
Division name	Division of Immunology
Zip code
Address	2-10-1 Okura, Setagaya-ku, Tokyo, Japan
TEL	03-5494-7035
Homepage URL
Email	uchiyama-t@ncchd.go.jp

Sponsor
Institute	National Center for Child Heath and Development
Institute
Department

Funding Source
Organization	Japan Agency for Medical Research and Development
Organization
Division
Category of Funding Organization	Japanese Governmental office
Nationality of Funding Organization

Other related organizations
Co-sponsor
Name of secondary funder(s)

IRB Contact (For public release)
Organization
Address
Tel
Email

Secondary IDs
Secondary IDs	NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions

Other administrative information
Date of disclosure of the study information	2018 Year 01 Month 15 Day

Related information
URL releasing protocol
Publication of results	Unpublished

Result
URL related to results and publications
Number of participants that the trial has enrolled
Results
Results date posted
Results Delayed
Results Delay Reason
Date of the first journal publication of results
Baseline Characteristics
Participant flow
Adverse events
Outcome measures
Plan to share IPD
IPD sharing Plan description

Progress
Recruitment status	No longer recruiting
Date of protocol fixation	2017 Year 10 Month 06 Day
Date of IRB	2017 Year 10 Month 19 Day
Anticipated trial start date	2018 Year 01 Month 17 Day
Last follow-up date	2025 Year 03 Month 31 Day
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Other
Other related information

Management information
Registered date	2018 Year 01 Month 14 Day
Last modified on	2021 Year 03 Month 15 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000035089