UMIN-CTR Clinical Trial

Basic information
Public title	A Prospective Study of Diagnosis and Therapeutics in Intraocular Malignant Lymphoma
Acronym	A Prospective Study of Diagnosis and Therapeutics in Intraocular Malignant Lymphoma
Scientific Title	A Prospective Study of Diagnosis and Therapeutics in Intraocular Malignant Lymphoma
Scientific Title:Acronym	A Prospective Study of Diagnosis and Therapeutics in Intraocular Malignant Lymphoma
Region	Japan

Condition
Condition	Uveitis suspected as Intraocular Malignant Lymphoma
Classification by specialty	Hematology and clinical oncology Ophthalmology Radiology
Classification by malignancy	Malignancy
Genomic information	NO

Objectives
Narrative objectives1	1) We perform vitrectomy to obtain the vitreous samples of uveitis suspected as intraocular malignant lymphoma (IOL), and determine the diagnosis of IOL according to the diagnostic criteria we determined. By following-up the cases, we evaluate the accuracy of the diagnostic criteria.
Basic objectives2	Others
Basic objectives -Others	2) We perform the treatments (intraocular methotrexate injections, systemic chemotherapy and low-dose whole brain radiation therapy (23.4Gy)) according to the treatment protocol we determined. By following-up the cases, we evaluate the efficacy of the protocol prospectively.
Trial characteristics_1	Confirmatory
Trial characteristics_2	Pragmatic
Developmental phase	Not applicable

Assessment
Primary outcomes	Diagnostic efficacy (sensitivity) of the diagnostic criteria Local recurrence ratio, systemic recurrence ratio, overall survival, progression-free survival
Key secondary outcomes	Classification of the papanicolaou staing of the vitrecous specimens, concentration of IL10/IL-6 of vitreous samples, IgH monoclonarity, final visual acuity, site of systemic dissemination, term during therapy and recurrence

Base
Study type	Interventional

Study design
Basic design	Parallel
Randomization	Non-randomized
Randomization unit
Blinding	Open -no one is blinded
Control	Active
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment

Intervention
No. of arms	4
Purpose of intervention	Treatment
Type of intervention	Medicine Other
Interventions/Control_1	1)Primary Intraocular lymphoma (IOL) only with primary systemic malignant lymphoma (ML): intravitreal injection of 0.4mg of MTX(totally 10times, once a week for 2 months and once a month for 2 months)+ R-MPV therapy (1st day:rituximab 375mg/m2, 2nd day: oncovin 1.4mg/m2 (maximum 2mg)+MTX 3.5g/m2, 1-7day: procarbazine 100mg/m2 (odd number course only)) 5-7 course + whole-brain radiotherapy (totally 23.4 Gy) + High dose Ara C therapy 2 course (High dose cytarabine 3 g/m2/day (maximum daily dose 6g) for 2 days). Systemic chemotherapy will be performed repeatedly 5 courses, one course in every 2 or 3 weeks.
Interventions/Control_2	2)Primary Intraocular lymphoma (IOL) with primary systemic malignant lymphoma (ML): intravitreal injection of 0.4mg of MTX(totally 10times, once a week for 2 months and once a month for 2 months)+ R-MPV therapy (1st day:rituximab 375mg/m2, 2nd day: oncovin 1.4mg/m2 (maximum 2mg)+MTX 3.5g/m2, 1-7day: procarbazine 100mg/m2 (odd number course only)) 5-7 course + whole-brain radiotherapy (totally 23.4-45 Gy) + High dose Ara C therapy 2 course (High dose cytarabine 3 g/m2/day (maximum daily dose 6g) for 2 days). Systemic chemotherapy will be performed repeatedly 5 courses, one course in every 2 or 3 weeks.
Interventions/Control_3	In cases of recurrence of intraocular lymphoma without systemic lymphoma: intravitreal injection of 0.4mg of MTX (totally 10 times, once a week for 2 months and once a month for 2 months) only.
Interventions/Control_4	In cases of intraocular lymphoma with systemic lymphoma or with the previous history of systemic lymphoma: Local injection of MTX (totally 10 times, once a week for 2 months and once a month for 2 months, systemic chemotherapy, irradiation (Stem cell transplantation should be considered. Contents of chemotherapy are not specified.)
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10

Eligibility
Age-lower limit	20 years-old <=
Age-upper limit	80 years-old >=
Gender	Male and Female
Key inclusion criteria	Age: 20-75 years old Selection criteria 1) cases with uveal inflammation, which is suspected as intraocular malignant lymphoma, and vitreous biopsy was done for diagnostic purposes. 2) Diagnostic criteria for intraocular lymphoma is as follows. (a) the vitreous fluid cytology (class 5) 3 points (Class 4) 2 points (Class 3) 1 point (b) IL-10/IL-6 (>1) or IL-10> 50pg/ml) 2 points (c) IgH monoclonality 2 points (d) FACS (distribution of kappa and lambda) 2 points (e) funduscopic findings that are characteristic of intraocular lymphoma (the aurora-like vitreous opacity or patchy cell infiltration of the retina (often with serous retinal detachment)). 1 point (f) the pathological diagnosis of malignant lymphoma of the eye or other organs before. 1 point If the sum of these 6 items is more than 4 points, we diagnose intraocular lymphoma. 3) adaptation of the treatment protocol: Ccr> 50
Key exclusion criteria	Except for performance status 4
Target sample size	150

Research contact person
Name of lead principal investigator	1st name RIE Middle name Last name TANAKA
Organization	University of Tokyo Hospital
Division name	Ophthalmology
Zip code	113-8655
Address	7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
TEL	03-3815-5411
Email	rtanaka-ymn@umin.ac.jp

Public contact
Name of contact person	1st name RIE Middle name Last name TANAKA
Organization	University of Tokyo Hospital
Division name	Ophthalmology
Zip code	113-8655
Address	7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
TEL	03-3815-5411
Homepage URL
Email	rtanaka-ymn@umin.ac.jp

Sponsor
Institute	Deportment of Ophthalmology, University of Tokyo Hospital
Institute
Department

Funding Source
Organization	Deportment of Ophthalmology, University of Tokyo Hospital
Organization
Division
Category of Funding Organization	Self funding
Nationality of Funding Organization	Japan

Other related organizations
Co-sponsor	Cancer institute hospital of Japanese Foundation For Cancer Research
Name of secondary funder(s)

IRB Contact (For public release)
Organization	The Research Ethics Committee of the Graduate School of Medicine and Faculty of Medicine at The University of Tokyo
Address	7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
Tel	03-5841-0818
Email	ethics@m.u-tokyo.ac.jp

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	東京大学付属病院眼科（東京都）

Other administrative information
Date of disclosure of the study information	2012 Year 04 Month 23 Day

Related information
URL releasing protocol
Publication of results	Published

Result
URL related to results and publications	https://onlinelibrary.wiley.com/doi/full/10.1111/bjh.14848
Number of participants that the trial has enrolled	17
Results	17 patients initiated and 16 completed the treatment. CNS relapse occurred in 2 and intraocular relapse in 3. 4-year PFS was 74.9% and 4-year OS was 86.3%. Of 11 patients without CNS involvement, 1 had CNS relapse and 3 intraocular relapse, and 4-year PFS was 72.7% and 4-year OS was 88.9%. No patients developed dementia/leukoencephalopathy. The combination of intravitreal chemotherapy, systemic chemotherapy and rdWBRT for B-cell PIOL showed a potential to reduce CNS relapse and improved 4-year PFS and OS.
Results date posted	2020 Year 05 Month 09 Day
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	2009 Year 01 Month 01 Day
Date of IRB	2008 Year 11 Month 21 Day
Anticipated trial start date	2009 Year 01 Month 01 Day
Last follow-up date	2023 Year 11 Month 21 Day
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Other
Other related information	Kaburaki T, Taoka K, Matsuda J, Yamashita H, Matsuda I, Tsuji H, Tanaka R, Nakazaki K, Nakamura F, Kamiya K, Kurokawa M, Ohtomo K, Aihara M. Combined intravitreal methotrexate and immunochemotherapy followed by reduced-dose whole-brain radiotherapy for newly diagnosed B-cell primary intraocular lymphoma. Br J Haematol. 2017 Oct;179(2):246-255. doi: 10.1111/bjh.14848.

Management information
Registered date	2012 Year 04 Month 23 Day
Last modified on	2021 Year 05 Month 14 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000002307