UMIN-CTR Clinical Trial

Basic information
Official scientific title of the study	Development of treosulfan-based conditioning regimen for congenital metabolic diseases; Phase I study
Title of the study (Brief title)	Development of treosulfan-based conditioning regimen for congenital metabolic diseases; Phase I study
Region	Japan

Condition
Condition	Mucopolysaccharidosis type I (Herler syndrome), type II (Hunter syndrome)
Classification by specialty	Pediatrics
Classification by malignancy	Others
Genomic information	NO

Objectives
Narrative objectives1	To determine the recommended dose of treosulfan when combined with low-dose irradiation, fludarabine, thymoglobulin for preparative regimen in patients with mucopolysaccharidosis
Basic objectives2	Safety
Basic objectives -Others
Trial characteristics_1	Confirmatory
Trial characteristics_2	Explanatory
Developmental phase	Phase I

Assessment
Primary outcomes	The incidence of severe RRT (Grade III/IV) on day 28 after HSCT with Treosulfan as a conditioning regimen.
Key secondary outcomes	Regimen-related toxicity, engraftment rate, survival rate at 28 days posttransplant, survival rate at 100 days posttransplant, chimeric study, GVHD, hepatic SOS, event-free survival and overall survival at 1 year posttransplant.

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
Interventions/Control_1	Treosulfan 14 g/m2, intravenous, day -6 -5 -4
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 and Female
Key inclusion criteria	1. Mucopolysaccharidosis type I (Herler syndrome), type II (Hunter syndrome) 2. Body weight; equal or more than 10 kg 3. ECOG performance status; 0 or 1 4. The transplant should be the first one for the patient. Retransplantation is acceptable under the following conditions; after over 6 months from previous transplantation, and has no effect of previous preconditioning regimen 5. One of the following stem cell donor is available 1) 6/6 or 5/6 (either class I or class II) HLA-A/B/DR serologically matched related bone marrow 2) 6/6 HLA-A/B/DR allelic matched or HLA-DR/DRB1 serologically/allelic mismatched unrelated bone marrow 3) Cord blood units with 6/6, 5/6, or 4/6 HLA serologically match and nucleated cell dose equal or more than 3.5 x 10e7/kg, and CD34+ cell dose equal or more than 1.0 x 10e5/kg 6. Major organ dysfunction (laboratory data) 1) Ejection fraction at rest (UCG); equal or more than 50% 2) Arterial oxygen saturation without oxygen supplementation; equal or greater than 93% 3) Serum creatinine < 1.3 mg/dl 4) Total bilirubin <1.6 mg/dl or AST(GOT) < 2 x normal of each institution 7. Patients without following active infections 1) Pathogen-proven bacterial infection requiring antimicrobial treatment 2) Imaging study (XP, CT, US, MRI) manifested infectious foci requiring antimicrobial treatment 3) Abscess formation or necrotizing infection 4) Viral infection necessitating systemic antiviral agents 5) Culture-positive or PCR-positive tuberculosis/non-tuberculous mycobacterial infection 6) Pneumocystis pneumonia 7) Meningitis, Encephalitis, Encephalopathy 8) Protozoan infection 9) Intraocular fungal infection 8. No previous history of hypersensitivity to the following drugs that are used for conditioning or prophylaxis of GVHD Treosulfan (L-threitol-1,4-bis-methanesulfonate; dihydroxybusulfan) Fludarabine Antithymocyte globulin Cyclosporine Methotrexate Tacrolimus
Key exclusion criteria	1. Down syndrome 2. HIV-positivity
Target sample size	12

Research contact person
Name of lead principal investigator	Shunichi Kato
Organization	Tokai University School of Medicine
Division name	Department of Cell Transplantation and Regenerative Medicine
Address	143, Shimokasuya, Isehara, Kanagawa, 259-1193, Japan
TEL	0463-93-1121
Email	skato@is.icc.u-tokai.ac.jp

Public contact
Name of contact person	Hiromasa Yabe
Organization	Tokai University School of Medicine
Division name	Department of Cell Transplantation and Regenerative Medicine
Address	143, Shimokasuya, Isehara, Kanagawa, 259-1193, Japan
TEL	0463-93-1121
Homepage URL
Email	yabeh@is.icc.u-tokai.ac.jp

Sponsor
Institute	Tokai University School of Medicine
Institute
Department

Funding Source
Organization	Government of Japan
Organization
Division
Category of Funding Organization	Japanese Governmental office
Nationality of Funding Organization	Japan

Other related organizations
Co-sponsor	1. School of Human Health Science Faculty of Medicine Kyoto University 2. Department of Pediatrics, Japanese Red cross Nagoya Daiichi Hospital 3. Department of Pediatrics, Nihon University
Name of secondary funｄer(s)

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	東海大学病院（神奈川県） 京都大学病院（京都府） 名古屋第一赤十字病院（愛知県） 日本大学病院（東京都）

Other administrative information
Date of disclosure of the study information	2013 Year 01 Month 15 Day

Progress
Recruitment status	Terminated
Date of protocol fixation	2013 Year 06 Month 24 Day
Anticipated trial start date	2013 Year 06 Month 24 Day
Last follow-up date	2014 Year 12 Month 23 Day
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Related information
URL releasing protocol
Publication of results	Unpublished
URL releasing results
Results
Other related information

Management information
Registered date	2013 Year 01 Month 11 Day
Last modified on	2019 Year 01 Month 16 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000011433