UMIN-CTR Clinical Trial

Basic information
Official scientific title of the study	Efficacy and safety study of defibrotide (DF) for the prophylaxis of venoocclusive disease (VOD).
Title of the study (Brief title)	Efficacy and safety study of defibrotide (DF) for the prophylaxis of venoocclusive disease (VOD).
Region	Japan

Condition
Condition	Veno Occlusive Disease
Classification by specialty	Hematology and clinical oncology Pediatrics
Classification by malignancy	Malignancy
Genomic information	NO

Objectives
Narrative objectives1	[Primary objective] To evaluate efficacy of DF for the prophylaxis of VOD following allogeneic hematopoietic stem cell transplantation in both pediatric and adult patients. [Secondary objectives] To evaluate safety of DF. To evaluate pharmacokinetics of DF in both pediatric and adult patients.
Basic objectives2	Efficacy
Basic objectives -Others
Trial characteristics_1
Trial characteristics_2
Developmental phase

Assessment
Primary outcomes	Incidence of VOD until day 30 post stem cell transplant in patients who undergo prophylaxis with DF. Principal or other investigator should evaluate the development of VOD according to the revised Seattle criteria. VOD is defined as those who meet at least 2 of the following criteria by day 35 post stem cell transplant. -T-Bil>=2mg/dL -Hepatomegaly -Right hypochondriac pain -Ascites -Unexplained weight gain of>5% from baseline.
Key secondary outcomes	To compare the following outcomes both in DF prophylaxis group and control (no prophylaxis) group. 1)Incidence of VOD at day 30, 100 post stem cell transplant. 2)Incidence of VOD according to the Baltimore criteria at day 30, 100 post stem cell transplant. 3)Severity of VOD in patients who developed VOD. 4)Incidence of total, grade II-IV, and III-IV acute GVHD at day 100 post stem cell transplant. 5)Survival at day 100, 180 post stem cell transplant. 6)Survival at day 100, 180 post stem cell transplant in patients who developed VOD. 7)Incidence and severity of adverse events and drug-related adverse event. 8)Date of engraftment. 9)Remission status of the original disease at day 30, 100, and 180 after stem cell transplant in patients with malignancy.

Base
Study type	Interventional

Study design
Basic design	Parallel
Randomization	Randomized
Randomization unit	Individual
Blinding	Open -no one is blinded
Control	No treatment
Stratification	YES
Dynamic allocation	YES
Institution consideration	Institution is not considered as adjustment factor.
Blocking	NO
Concealment	Central registration

Intervention
No. of arms	2
Purpose of intervention	Treatment
Type of intervention	Medicine
Interventions/Control_1	Defibrotide(DF-01) 1)Intravenous infusion of DF 6.25 mg/kg/dose over 2 hours,4 doses per day (every 6 hours). 2)From 1 day before starting conditioning regimen until day 30 post stem cell transplant (for a maximum of 100 days after transplantation).
Interventions/Control_2	Control Group(non-administration group):Standard Treatment
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	50 years-old >
Gender	Male and Female
Key inclusion criteria	1.younger than 50 years old (at informed consent). 2.Primary disease is one of the following: 1)malignant tumor not in remission 2)malignant tumor in remission. 3)osteopetrosis 4)non-malignant disease other than osteopetrosis 3.Patients with one or more following risk factors of VOD who undergo allogeneic stem cell transplantation with myeloablative conditioning regimen. -Second myeloablative transplant -Not in remission at transplant -Performance status (ECOG) of 2 or more. -Conditioning regimen including Bu/Mel or Bu/Cy. -Liver dysfunction before stem cell transplant. -Positive for anti-HCV antibody. -Administration of gemutuzumab ozogamicin within 100 days before stem cell transplant. -Osteopetrosis 4.Witten informed consent to participate in the study from the subject or legally acceptable representative before screening tests.
Key exclusion criteria	1.Using medication that increases risk of hemorrhage. 2.Acute bleeding that is not controlled. 3.Unstable hemodynamic status that require more than one vasopressor or decreased mean atrial pressure (MAP). 4.Complicated with viral fulminant hepatitis 5.Past history of organ transplant other than hematopoietic cell transplant. 6.Complicated with Grade IV GVHD 7.Females with pregnancy, breastfeeding, possible pregnancy. Male who will not consent contraception 8.Judged as inappropriate for participating in the study by the principal or other investigator for other reasons.
Target sample size	75

Research contact person
Name of lead principal investigator	Atsushi Kikuta
Organization	Fukushima Medical University Hospital
Division name	Clinical Oncology Center/Children's Oncology Division
Address	1 Hikariga-oka, Fukushima City 960-1295, JAPAN
TEL	024-547-1111
Email	akikuta@fmu.ac.jp

Public contact
Name of contact person	Miwa Izutsu
Organization	CTD Inc.
Division name	-
Address	3-3-2Tsukiji,Chuo-ku,Tokyo,140-0045,Japan
TEL	03-6228-4835
Homepage URL
Email	chosei@fmu-df.jp

Sponsor
Institute	Fukushima Medical University Hospital Atsushi Kikuta
Institute
Department

Funding Source
Organization	Ministry of Health, Labour and Welfare
Organization
Division
Category of Funding Organization
Nationality of Funding Organization

Other related organizations
Co-sponsor	LINK Phamaceuticals KK
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	公立大学法人 福島県立医科大学附属病院（福島県） 独立行政法人 国立がん研究センター中央病院（東京都） 国家公務員共済組合連合会　虎の門病院（東京都） 地方独立行政法人 神奈川県立病院機構 神奈川県立こども医療センター（神奈川県） 名古屋大学医学部附属病院（愛知県） 独立行政法人　国立病院機構 名古屋医療センター（愛知県） 公立大学法人 大阪市立大学医学部附属病院（大阪府） 兵庫医科大学病院（兵庫県）

Other administrative information
Date of disclosure of the study information	2014 Year 03 Month 18 Day

Progress
Recruitment status	Completed
Date of protocol fixation	2014 Year 01 Month 17 Day
Anticipated trial start date	2014 Year 05 Month 07 Day
Last follow-up date
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	2014 Year 03 Month 18 Day
Last modified on	2017 Year 02 Month 06 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000015712