UMIN-CTR Clinical Trial

Basic information
Official scientific title of the study	A study investigating the efficacy and safety of CNS prophylaxis with R-CHOP and high-dose methotrexate in patients with de novo diffuse large B-cell lymphoma who have high risk for CNS relapse.
Title of the study (Brief title)	A study investigating the efficacy and safety of CNS prophylaxis with R-CHOP and high-dose methotrexate in patients with de novo diffuse large B-cell lymphoma who have high risk for CNS relapse.
Region	Japan

Condition
Condition	Diffuse large B-cell lymphoma
Classification by specialty	Hematology and clinical oncology
Classification by malignancy	Malignancy
Genomic information	NO

Objectives
Narrative objectives1	To study the efficacy and safety of CNS prophylaxis (standard R-CHOP, intrathecal methotrexate, and high-dose methotrexate) in patients with de novo diffuse large B-cell lymphoma who have high risk for CNS relapse.
Basic objectives2	Efficacy
Basic objectives -Others
Trial characteristics_1	Exploratory
Trial characteristics_2
Developmental phase	Phase II

Assessment
Primary outcomes	2-year CNS relapse rate
Key secondary outcomes	Response rate, Relapse-free survival, 2-year survival rate, Safety

In outcomes field, the entry of just a few words such as "safety" or "efficiency" will not be accepted. Specify the name of outcome measures, including the time when you plan to measure. Usually, only one primary outcome is accepted. Write the other outcomes in "secondary outcomes" field.

Base
Study type	Interventional

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

Intervention
No. of arms	1
Purpose of intervention	Treatment
Type of intervention	Medicine
Interventions/Control_1	R-CHOP High-dose methotrexate Intrathecal methotrexate
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

In interventions field, include the details of interventions, such as duration, amount, and frequency. If the intervention includes prescription or use of medical devices, duration is required.

Eligibility
Age-lower limit	20 years-old <=
Age-upper limit	Not applicable
Gender	Male and Female
Key inclusion criteria	1. Histologically confirmed diffuse large B-cell lymphoma 2. High or high-intermediate IPI risk and stage III or IV 3. Patients aged >=20 years 4. Adequate organ function as follows; #1 Absolute neutrophil count >= 1000/mm3 #2 Platelet count >= 100,000/mm3 #3 Estimated EGFR >= 50 #4 AST and ALT levels <= 3 times the upper limit of the normal range #5 SpO2 >= 95% #6 Normal ECG #7 (If echocardiogram is done) Left ventricular ejection fraction > 50% #8 Karnofsky Performance Status >= 40 5. Patients who have at least one measurable lesion, or evaluable disease if there is no measurable lesion. Measurable lesion can be accurately measured in two dimensions orthogonal with each other by CT scan. Malignant lymph nodes are to be considered pathologically enlarged and measurable, a lymph node must be >=15mm in long axis or >=10mm in short axis when assessed by CT scan. Extranodal lesions must be accurately measured in at least one dimension as >=10mm by CT scan (CT scan slice thickness is no greater than 5mm; when CT scan have slice thickness >5mm, the minimum size should be twice the slice thickness). Evaluable disease is non-measurable lesions but can be confirmed as lymphoma by CT, MRI, PET or endoscopy. 6. Written informed consent
Key exclusion criteria	1. Primary CNS lymphoma (include intraocular lymphoma) or lymphoma with cns involvement on CT and/or MRI, or CSF examination on admission 2. Intravascular lymphoma, primary effusion lymphoma, mediastinal large B-cell lymphoma 3. Primary testicular lymphoma 4. Patients with peripheral bood involvement of lymphoma on admission 5. Prior treatment for lymphoma except lymph node biopsy and local radiation therapy 6. Presence of fluid in the third space (e.g. pleural effusions) 7. Patients with pre-existing renal insufficiency 8. Patients with another active malignancy 9. Patients with serious complications (malignant hypertension, congestive heart failure, coronary insufficiency, a new onset of myocardial infarction within 3 months, uncontrolled hyperglycemia, pulmonary fibrosis, interstitial pneumonia, etc) 10. Severe psychosis 11. Presence of uncontrollable active infection 12. Patients with allergy to drug used for conditioning regimen 13. Positive for HIV antibody, HCV antibody or HTLV-1 antibody 14. HBs antigen positive patients judged unfeasible to participate in this protocol in spite of the administration of antiviral drugs 15. Patients who are pregnant or lactating 16. Without any written consent from patients 17. Inadequate patients to enroll judged by investigators
Target sample size	100

Research contact person
Name of lead principal investigator	Yasuhiro Nagate
Organization	Osaka University Graduate School of Medicine
Division name	Department of Hematology and Oncology
Address	2-2, Yamadaoka, Suita, Osaka 565-0871 JAPAN
TEL	06-6879-3871
Email	nagate@bldon.med.osaka-u.ac.jp

Public contact
Name of contact person	Yasuhiro Nagate
Organization	Osaka University Graduate School of Medicine
Division name	Department of Hematology and Oncology
Address	2-2, Yamadaoka, Suita, Osaka 565-0871 JAPAN
TEL	06-6879-3871
Homepage URL
Email	nagate@bldon.med.osaka-u.ac.jp

Sponsor
Institute	Department of Hematology and Oncology, Osaka University Graduate School of Medicine
Institute
Department

Sponsor means an organization that is responsible for plan, deployment and report of the research including funding management. It doesn't mean funding agency". Therefore, all clinical trial should have the one.

Funding Source
Organization	None
Organization
Division
Category of Funding Organization	Self funding
Nationality of Funding Organization

Other related organizations
Co-sponsor
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	大阪大学医学部附属病院（大阪府） 府立成人病センター（大阪府） NTT西日本大阪病院（大阪府） 県立西宮病院（兵庫県） 大手前病院（大阪府） 市立芦屋病院（兵庫県） 市立池田病院（大阪府） 市立伊丹病院（兵庫県） 市立堺病院（大阪府） 市立吹田病院（大阪府） 市立豊中病院（大阪府） 住友病院（大阪府） 日生病院（大阪府） 市立箕面病院（大阪府） りんくう総合医療センター（大阪府） 八尾市立病院（大阪府） 関西労災病院（兵庫県） 国立病院大阪医療センター（大阪府） 医療法人　川崎病院（兵庫県） 川西市民病院（兵庫県）

Other administrative information
Date of disclosure of the study information	2014 Year 03 Month 28 Day

Progress
Recruitment status	Terminated
Date of protocol fixation	2014 Year 03 Month 13 Day
Anticipated trial start date	2014 Year 03 Month 28 Day
Last follow-up date
Date of closure to data entry	2015 Year 06 Month 09 Day
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 27 Day
Last modified on	2016 Year 04 Month 02 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-bin/icdr_e/ctr_view.cgi?recptno=R000015823