NCCH2201/MK013 trial

JRCT ID: jRCT2031220529

Registered date:23/12/2022

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: secondary central nervous system lymphoma
• Date of first enrollment: 15/12/2022
• Target sample size: 20
• Study type: Interventional
• Intervention(s): Tirabrutinib is administered orally under fasting conditions at a daily dose of 480mg.

Outcome(s)

• Primary Outcome: Objective response rate (centrally assessed)
• Secondary Outcome: Response rate(investigator assessed ), progression-free survival, overall survival, complete response rate, duration of response, and incidence of adverse events

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1)Subjects with B-cell non-Hodgkin's lymphoma, histopathologically diagnosed at the participating institutions. Patients with lymphoblastic lymphoma, Burkitt lymphoma, high-grade B-cell lymphoma with MYC/ and BCL2 and/or BCL6 rearrangements, or high-grade B-cell lymphoma NOS are excluded. #Patients whose pathological specimens are obtained at another institution are eligible if it is confirmed to meet the criteria for pathology at the participating institution.
2)Presence of CNS involvement (brain, spinal cord, and cerebrospinal fluid) clinically and meets any of the following criteria [1] or [2], or both. [1] Brain or spinal cord involvement that is measurable (see 11.1.2. Defining measurable disease) on Gd contrast-enhanced MRI obtained within 28 days prior to enrollment [2]Cytologically confirmed tumor cells in cerebrospinal fluid within 28 days prior to enrollment.
3)Absence of lymphoma lesion out of the central nervous system (brain, spinal cord and cerebrospinal fluid) on FDG-PET/CT within 28 days prior to enrollment.
4)One or more prior anti-cancer chemotherapies including high-dose methotrexate therapy for SCNSL. Prior chemotherapies for SCNSL are not required if patients are intolerance to high-dose methotrexate therapy (age 75 years or older, CCr 50 mL/min or less, or Cr 1.5 mg/dL or higher prior to enrollment) .
5)Age 18 years or older at enrollment
6)Performance Status(ECOG) from 0 to 2.
7)Oral intake is feasible.

Exclude criteria

1)Patients who are unable to undergo gadollinium contrast-enhanced MRI due to Gd allergies to gadolinium, claustrophobia, etc.
2)Prior treatment with BTK inhibitors including tirabrutinib.
3)Those who received CYP3A4 inducers, P-gp inducers or potent CYP3A4 inhibitors within 14 days prior to enrollment
4) Active double primary cancer (but not [1]-[3]): [1]completely resected following cancers: basal cell carcinoma, stage I squamous cell carcinoma, carcinoma in situ, intramucosal carcinoma, superficial bladder cancer, [2]gastrointestinal cancer curatively resected with ESD or EMR, and [3]other cancers with no recurrence for more than 2 years
5)Patients with concomitant or history of interstitial lung disease or pulmonary fibrosis diagnosed by imaging or clinical findings
6)Patients with uncontrolled complications and severe heart disease (cardiac disease of NYHA class III or higher, unstable conduction abnormalities, myocardial infarction/angina occurring in less than 180 days) that may affect protocol compliance, safety, or efficacy assessment.
7)Patients who are positive for either HIV antibody, HBs antigen, or HCV antibody but patients who are positive for HCV antibody but negative for HCV-RNA are not excluded.
8)Negative for HBs antigen, positive for HBs antibody or HBcantibody, and positive for HBV-DNA assay. However, if it is less than or equal to the detection sensitivity, patients are not excluded even during oral antiviral treatment.
9)Patients complicated with medical condition that markedly affect gastrointestinal function, such as malabsorption, malabsorption syndrome, and inflammatory bowel disease including ulcerative colitis, or patients who have undergone complete resection of the stomach or small intestine, or who have developed partial or complete intestinal obstruction.
10)Patients with infections requiring systemic treatment.
11)Patients with a history of allogeneic hematopoietic stem cell transplantation
12)Women who are pregnant, breastfeeding and need to continue breastfeeding in the future, and women who may be pregnant.
13)Patients with a history of serious allergy or anaphylaxis in the past.
14)Patients who are deemed inappropriate for participation in the study by the principal investigator or sub-investigator

Related Information

• Primary Sponsor: Wataru Munakata
• Source(s) of Monetary Support: ONO PHARMACEUTICAL CO., LTD.