UMIN-CTR Clinical Trial

Public title

Efficacy and safety study of defibrotide (DF) for the prophylaxis of venoocclusive disease (VOD).

Acronym

Efficacy and safety study of defibrotide (DF) for the prophylaxis of venoocclusive disease (VOD).

Scientific Title

Efficacy and safety study of defibrotide (DF) for the prophylaxis of venoocclusive disease (VOD).

Scientific Title:Acronym

Efficacy and safety study of defibrotide (DF) for the prophylaxis of venoocclusive disease (VOD).

Region

Japan

Condition

Veno Occlusive Disease

Classification by specialty

Hematology and clinical oncology

Pediatrics

Classification by malignancy

Malignancy

Genomic information

NO

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

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.

Study type

Interventional

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

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

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

Name of lead principal investigator

1st name
Middle name
Last name	Atsushi Kikuta

Organization

Fukushima Medical University Hospital

Division name

Clinical Oncology Center/Children's Oncology Division

Zip code

Address

1 Hikariga-oka, Fukushima City 960-1295, JAPAN

TEL

024-547-1111

Email

akikuta@fmu.ac.jp

Name of contact person

1st name
Middle name
Last name	Miwa Izutsu

Organization

CTD Inc.

Division name

-

Zip code

Address

3-3-2Tsukiji,Chuo-ku,Tokyo,140-0045,Japan

TEL

03-6228-4835

Homepage URL

Email

chosei@fmu-df.jp

Institute

Fukushima Medical University Hospital
Atsushi Kikuta

Institute

Department

Personal name

Organization

Ministry of Health, Labour and Welfare

Organization

Division

Category of Funding Organization

Nationality of Funding Organization

Co-sponsor

LINK Phamaceuticals KK

Name of secondary funder(s)

Organization

Address

Tel

Email

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

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）

Date of disclosure of the study information

2014

Year

03

Month

18

Day

URL releasing protocol

Publication of results

Unpublished

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

Recruitment status

Completed

Date of protocol fixation

2014

Year

01

Month

17

Day

Date of IRB

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

Other related information

Registered date

2014

Year

03

Month

18

Day

Last modified on

2017

Year

02

Month

06

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000015712