UMIN-CTR Clinical Trial

Public title

Efficacy and Safety of Ruxolitinib single treatment in patients with chronic active Epstein-Barr virus infection (Phase II) (investigator-initiated study)

Acronym

Efficacy and Safety of Ruxolitinib for CAEBV patients (Phase II)

Scientific Title

Efficacy and Safety of Ruxolitinib single treatment in patients with chronic active Epstein-Barr virus infection (Phase II) (investigator-initiated study)

Scientific Title:Acronym

Efficacy and Safety of Ruxolitinib for CAEBV patients (Phase II)

Region

Japan

Condition

chronic active Epstein-Barr virus infection
CAEBV

Classification by specialty

Hematology and clinical oncology

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

To investigate efficacy and safety of ruxolitinib, JAK1/2 inhibitor, as single treatment for patients with chronic active Epstein-Barr virus infection.

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Exploratory

Trial characteristics_2

Developmental phase

Phase II

Primary outcomes

Percentage of participants with complete response (CR) at week 8 or early termination.

Key secondary outcomes

Percentage of participants with complete response (CR) at week 4.
Overall response rate at week 8 or early termination.
Adverse event.
Plasma drug concentration.
Epstein-Barr virus DNA quantification .
Plasma cytokine concentration.

Study type

Interventional

Basic design

Single arm

Randomization

Non-randomized

Randomization unit

Blinding

Open -no one is blinded

Control

Uncontrolled

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

1

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

ruxolitinib tablet

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

Age-lower limit

13

years-old

<=

Age-upper limit

Not applicable

Gender

Male and Female

Key inclusion criteria

Subjects diagnosed as CAEBV under "Guidelines for Clinical Practice for Chronic Active EB Virus Infection and Related Diseases 2016" and matched all criteria below;
(1) with >= 1x10^2.5 copies/mcg DNA of EBV DNA load in peripheral blood measured within 8 weeks prior to registration (only the central measuring institution are acceptable).
(2) with confirmed EBV infection on T- or NK-cells in tissue lesions or in peripheral blood.
(3) with >= 3 months of either continuous or intermittent systemic inflammatory symptoms: persistent fever, liver dysfunction, multiple lymphadenopathy, progressive skin lesions, vasculitis, neuritis, uveitis, enteritis etc. However, subjects with hypersensitivity to mosquito bites and Hydroa Vacciniforme-like eruptions without sustained systemic inflammatory symptoms are not diagnosed with CAEBV and excluded.
(4) negative for the following diseases:
Congenital or acquired immunodeficiency, autoimmune/inflammatory disease, connective tissue disease, malignant lymphoma, leukemia, iatrogenic immunodeficiency.
(5) having active disease during observation period: having fever and/or liver dysfunction defined below.
1) having fever without any other causes (>= 37.5 deg. of axillary temperature) in >= 2 days during 5-day observation.
2) having liver dysfunction defined as increase of ALT levels to two times higher than the upper limit of normal on at least two consecutive occasions.
ALT should be measured twice within 28 days before registration, and both should match the criteria. The latter measurement should be performed within 7 days before registration.
(6) with life expectancy of >= 3 months.
(7) fulfilling the following cell count in peripheral blood in the latest examination within 7 days before registration.
1) >= 500/microL of Neutrophil
2) >= 50,000/microL of Platelet
(8) 13 years of age or older at obtaining informed consent.
(9) who obtained written informed consent from the subjects themselves or legal representative.

Key exclusion criteria

Subjects matched any of the followings are excluded;
(1) pathological or clinical lymphoid neoplasm derived from EBV-infected T- or NK-cells of CAEBV.
(2) anti-VCA-IgM Ab positive (difficult to distinguish from infectious mononucleosis).
(3) with history taking JAK 1/2 inhibitors.
(4) with malignant neoplasm or history of them within the last 5 years, though cervical intraepithelial carcinoma, basal cell carcinoma or squamous cell carcinoma of the skin treated properly, fully resected gastric intramucosal carcinoma can be accepted.
(5) with unstoppable treatment with >200 mg/day fluconazole or strong CYP3A4 inducer (rifampicin, St. John's wart etc) at the beginning of study drug administration (excl. topical).
(6) with infectious diseases requiring systemic antibiotics or antivirals.
(7) with tuberculosis or HIV-positive.
(8) with active hepatitis matching any of the following within 84 days before registration;
-HBs Ag-positive
-HBc Ab-positive or HBs Ab-positive with >= 20 IU/mL (1.3 Log IU/mL, the same below) of peripheral blood HBV DNA load
HBs Ag-negative, HBs Ab-positive, HBc Ab-negative and history of the vaccination for HBV are treated as uninfected ones.
-HCV Ab-positive (except when confirmed HCV-RNA-negative).
* There are some conditions for judgment of HBV infection.
(9) with cardiac disease of NYHA class IV.
(10) having been treated with other anticancer drug (e.g. etoposide) within 14 days prior to registration.
(11) with history of hypersensitivity to ingredients of ruxolitinib tablet.
(12) having been treated with another investigational medication within 12 weeks prior to registration.
(13) female who are pregnant, have possibility of pregnancy, or are currently breastfeeding.
(14) difficult to take oral tablet.
(15) judged unsuitable for participation by investigator or sub-investigator.

Target sample size

10

Name of lead principal investigator

1st name	Ayako
Middle name
Last name	Arai

Organization

St. Marianna University School of Medicine

Division name

Department of Hematology and Oncology

Zip code

216-8511

Address

2-16-1, Sugao, Miyamae-ku, Kawasaki, Kanagawa

TEL

044-977-8111

Email

ara.hema@tmd.ac.jp

Name of contact person

1st name	Yuki
Middle name
Last name	Ohta

Organization

St. Marianna University School of Medicine

Division name

Center for Clinical and Translational Science

Zip code

216-8511

Address

2-16-1, Sugao, Miyamae-ku, Kawasaki, Kanagawa

TEL

044-977-8111

Homepage URL

Email

mariadc_caebv@marianna-u.ac.jp

Institute

St. Marianna University School of Medicine

Institute

Department

Personal name

Organization

Japan Agency for Medical Research and Development (AMED)

Organization

Division

Category of Funding Organization

Japanese Governmental office

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

St. Marianna University Group Institutional Review Board

Address

2-16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa

Tel

044-977-8111

Email

chikenjimu@marianna-u.ac.jp

Secondary IDs

YES

Study ID_1

TMD18-HEMA-201

Org. issuing International ID_1

Tokyo Medical and Dental University

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

東京医科歯科大学医学部附属病院（東京都）
大阪母子医療センター（大阪府）
聖マリアンナ医科大学病院（神奈川県）
九州大学病院（福岡県）

Date of disclosure of the study information

2018

Year

12

Month

15

Day

URL releasing protocol

Publication of results

Unpublished

URL related to results and publications

Number of participants that the trial has enrolled

9

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

2018

Year

11

Month

07

Day

Date of IRB

2018

Year

11

Month

27

Day

Anticipated trial start date

2019

Year

01

Month

09

Day

Last follow-up date

2022

Year

03

Month

31

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2018

Year

12

Month

03

Day

Last modified on

2022

Year

12

Month

05

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000039806