Phase I Study Evaluating Tolerability, Safety, Pharmacokinetics, and Efficacy of Combined ONO-4059 and R-MPV Therapy for PCNSL

October 5, 2026 updated by: Ono Pharmaceutical Co., Ltd.

A Multicenter, Phase I, Open-label, Uncontrolled Study of ONO-4059 in Combination With Rituximab, Methotrexate, Procarbazine, and Vincristine (R-MPV) Therapy for Untreated Primary Central Nervous System Lymphoma (PCNSL)

To confirm the tolerability and safety of combined administration of ONO-4059 and R-MPV therapy in untreated PCNSL patients.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

20

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Japan
    • Aichi-ken
      • Nagoya, Aichi-ken, Japan
        • Nagoya City University Hospital
      • Nagoya, Aichi-ken, Japan
        • Aichi Cancer Center
    • Akita
      • Akita, Akita, Japan
        • Akita University Hospital
    • Chiba
      • Urayasu-shi, Chiba, Japan
        • Juntendo University Urayasu Hospital
    • Fukuoka
      • Fukuoka, Fukuoka, Japan
        • Kyushu University Hospital
      • Fukuoka, Fukuoka, Japan
        • Fukuoka University Hospital
      • Kitakyushu-shi, Fukuoka, Japan
        • Hospital of the University of Occupational and Environmental Health,Japan
      • Kurume-shi, Fukuoka, Japan
        • Kurume University Hospital
    • Fukushima
      • Fukushima, Fukushima, Japan
        • Fukushima Medical University Hospital
    • Gifu
      • Gifu, Gifu, Japan
        • Gifu University Hospital (Tokai National Higher Education and Research System)
    • Gunma
      • Maebashi, Gunma, Japan
        • Gunma University Hospital
    • Hokkaido
      • Sapporo, Hokkaido, Japan
        • Sapporo Medical University Hospital
    • Hyōgo
      • Kobe, Hyōgo, Japan
        • Kobe City Medical Center General Hospital
      • Nishinomiya-shi, Hyōgo, Japan
        • Hyogo Medical University Hospital
    • Ibaraki
      • Tsukuba, Ibaraki, Japan
        • University of Tsukuba Hospital
    • Ishikawa-ken
      • Kahoku-gun, Ishikawa-ken, Japan
        • Kanazawa Medical University Hospital
    • Kagawa-ken
      • Kita-gun, Kagawa-ken, Japan
        • Kagawa University Hospital
    • Kanagawa
      • Kawasaki-shi, Kanagawa, Japan
        • St. Marianna University Hospital
      • Yokohama, Kanagawa, Japan
        • Yokohama City University Hospital
    • Kochi
      • Nankoku-shi, Kochi, Japan
        • Kochi Medical School Hospital
    • Miyazaki
      • Miyazaki, Miyazaki, Japan
        • University of Miyazaki Hospital
    • Nagasaki
      • Nagasaki, Nagasaki, Japan
        • NAGASAKI University Hospital
    • Nara
      • Ikoma-shi, Nara, Japan
        • Kindai University Nara Hospital
      • Kashihara-shi, Nara, Japan
        • Nara Medical University
    • Niigata
      • Niigata, Niigata, Japan
        • Niigata University Medical & Dental Hospital
    • Oita Prefecture
      • Yufu-shi, Oita Prefecture, Japan
        • Oita University Hospital
    • Okayama-ken
      • Kurashiki-shi, Okayama-ken, Japan
        • Kurashiki Central Hospital
    • Osaka
      • Osaka, Osaka, Japan
        • Osaka International Cancer Institute
      • Osakasayama-shi, Osaka, Japan
        • Kindai University Hospital
      • Suita-shi, Osaka, Japan
        • Osaka University Hospital
    • Saga-ken
      • Saga, Saga-ken, Japan
        • Saga University Hospital
    • Saitama
      • Kawagoe-shi, Saitama, Japan
        • Saitama Medical Center
    • Shizuoka
      • Sunto-gun, Shizuoka, Japan
        • Shizuoka Cancer Center
    • Tochigi
      • Shimotsuga-gun, Tochigi, Japan
        • Dokkyo Medical University Hospital
    • Tokyo
      • Bunkyo-ku, Tokyo, Japan
        • Institute of Science Tokyo Hospital
      • Koto-ku, Tokyo, Japan
        • The Cancer Institute Hospital of JFCR
      • Midorichō, Tokyo, Japan
        • National Hospital Organization Disaster Medical Center
      • Minato-ku, Tokyo, Japan
        • The Jikei University Hospital
      • Minato-ku, Tokyo, Japan
        • Toranomon Hospital
      • Shinjuku-ku, Tokyo, Japan
        • Tokyo Medical University Hospital
      • Shinjuku-ku, Tokyo, Japan
        • Tokyo Women's Medical University Hospital
    • Toyama
      • Toyama, Toyama, Japan
        • Toyama University Hospital
    • Yamaguchi
      • Ube-shi, Yamaguchi, Japan
        • Yamaguchi University Hospital
    • Yamanashi
      • Chuo-shi, Yamanashi, Japan
        • University of Yamanashi Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients diagnosed with PCNSL
  • Patients who have not received treatment for PCNSL in the past
  • Patients with ECOG Performance Status 0-2
  • Patients expected to survive for 6 months or more

Exclusion Criteria:

  • Patients with intraocular PCNSL without brain lesions
  • Patients are unable to swallow oral medications

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Tirabrutinib + R-MPV in patients with newly diagnosed, treatment naïve PCNSL
Drug: ONO-4059

Specified dose, once daily

Other Names:
  • Tirabrutinib Hydrochloride
Drug: Rituximab

Specified dose on specified days

Drug: Methotrexate

Specified dose on specified days

Drug: Procarbazine

Specified dose on specified days

Drug: Vincristine

Specified dose on specified days

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Tolerability evaluation
Time Frame: 29 Days

The number of subjects who experienced adverse events and side effects will be tallied. In the tolerability evaluation part, the number of subjects who experienced Dose Limiting Toxicity(DLT) will be tallied
29 Days
Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) during induction
Time Frame: 2 years

Adverse events at each visit with the NCI CTCAE v5.0 used as a guide for the grading of severity.
2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Summary of plasma tirabrutinib concentration at trough and post 2 hours dosing
Time Frame: 30days
30days
Duration of response (DOR)
Time Frame: 2 years

Duration of response is defined as the time between the date of first response (Complete response (CR), Complete response - unconfirmed (CRu), or partial response (PR) ) and the date of the first progressive disease(PD) according to the IPCG criteria, or date of death due to any cause, whichever occurs first.
2 years
Time to response (TTR)
Time Frame: 1 year

Time to response is defined as the time between the date of first administration of tirabrutinib and the date of first response (CR, CRu, or PR) as determined by IRC according to the IPCG criteria.
1 year
Best overall response (BOR)
Time Frame: 1 year

Best overall response based on independent review committee (IRC) response determination is defined as the best response and is derived programmatically based upon the visit responses determined by IRC from the date of administration of tirabrutinib to the date of PD as determined by IRC or the date of initiation of subsequent anticancer therapy for PCNSL, whichever occurs first.
1 year
Complete response rate (CRR)
Time Frame: 4 months

Complete response rate is defined as the proportion of patients with a best overall response of CR or CRu as determined by an independent review committee according to the IPCG criteria.
4 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Ono Pharmaceutical Co., Ltd.

Investigators

  • Study Director: Project Leader, Ono Pharmaceutical Co., Ltd.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 17, 2024

Primary Completion (Estimated)

April 28, 2028

Study Completion (Estimated)

August 31, 2028

Study Registration Dates

First Submitted

August 2, 2024

First Submitted That Met QC Criteria

August 2, 2024

First Posted (Actual)

August 7, 2024

Study Record Updates

Last Update Posted (Actual)

October 6, 2026

Last Update Submitted That Met QC Criteria

October 5, 2026

Last Verified

October 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ONO-4059-13
  • jRCT2071230124 (Registry Identifier: Japan Registry of Clinical Trials)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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