UMIN-CTR Clinical Trial

Basic information
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
Condition	chronic active Epstein-Barr virus infection CAEBV
Classification by specialty	Hematology and clinical oncology
Classification by malignancy	Others
Genomic information	NO

Objectives
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

Assessment
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.

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	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

Eligibility
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

Research contact person
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

Public contact
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

Sponsor
Institute	St. Marianna University School of Medicine
Institute
Department

Funding Source
Organization	Japan Agency for Medical Research and Development (AMED)
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	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
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
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）

Other administrative information
Date of disclosure of the study information	2018 Year 12 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	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

Progress
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
Other related information

Management information
Registered date	2018 Year 12 Month 03 Day
Last modified on	2022 Year 12 Month 05 Day

Link to view the page
URL(English)	https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000039806