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

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: Primary Central Nervous System Lymphoma
• Intervention / Treatment: Drug: Rituximab; Drug: Methotrexate; Drug: Vincristine; Drug: ONO-4059; Drug: Procarbazine

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Aichi
    • Nagoya-shi, Aichi, Japan
      • Nagoya City University Hospital
    • Nagoya-shi, Aichi, Japan
      • Aichi Cancer Center
  • Akita
    • Akita-shi, Akita, Japan
      • Akita University Hospital
  • Chiba
    • Urayasu-shi, Chiba, Japan
      • Juntendo University Urayasu Hospital
  • Fukuoka
    • Fukuoka-shi, Fukuoka, Japan
      • Kyushu University Hospital
    • Fukuoka-shi, 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-shi, Fukushima, Japan
      • Fukushima Medical University Hospital
  • Gifu
    • Gifu-shi, Gifu, Japan
      • Gifu University Hospital (Tokai National Higher Education and Research System)
  • Gunma
    • Maebashi-shi, Gunma, Japan
      • Gunma University Hospital
  • Hokkaido
    • Sapporo-shi, Hokkaido, Japan
      • Sapporo Medical University Hospital
  • Hyogo
    • Kobe-shi, Hyogo, Japan
      • Kobe City Medical Center General Hospital
    • Nishinomiya-shi, Hyogo, Japan
      • Hyogo Medical University Hospital
  • Ibaraki
    • Tsukuba-shi, Ibaraki, Japan
      • University of Tsukuba Hospital
  • Ishikawa
    • Kahoku-gun, Ishikawa, Japan
      • Kanazawa Medical University Hospital
  • Kagawa
    • Kita-gun, Kagawa, Japan
      • Kagawa University Hospital
  • Kanagawa
    • Kawasaki-shi, Kanagawa, Japan
      • St. Marianna University Hospital
    • Yokohama-shi, Kanagawa, Japan
      • Yokohama City University Hospital
  • Kochi
    • Nankoku-shi, Kochi, Japan
      • Kochi Medical School Hospital
  • Miyazaki
    • Miyazaki-shi, Miyazaki, Japan
      • University of Miyazaki Hospital
  • Nagasaki
    • Nagasaki-shi, Nagasaki, Japan
      • Nagasaki University Hospital
  • Nara
    • Ikoma-shi, Nara, Japan
      • Kindai University Nara Hospital
    • Kashihara-shi, Nara, Japan
      • Nara Medical University
  • Niigata
    • Niigata-shi, Niigata, Japan
      • Niigata University Medical & Dental Hospital
  • Oita
    • Yufu-shi, Oita, Japan
      • Oita University Hospital
  • Okayama
    • Kurashiki-shi, Okayama, Japan
      • Kurashiki Central Hospital
  • Osaka
    • Osaka-shi, Osaka, Japan
      • Osaka International Cancer Institute
    • Osakasayama-shi, Osaka, Japan
      • Kindai University Hospital
    • Suita-shi, Osaka, Japan
      • Osaka University Hospital
  • Saga
    • Saga-shi, Saga, 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
    • Midori-cho, 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 Women's Medical University Hospital
    • Shinjuku-ku, Tokyo, Japan
      • Tokyo Medical University Hospital
  • Toyama
    • Toyama-shi, Toyama, Japan
      • Toyama University Hospital
  • Yamaguchi
    • Ube-shi, Yamaguchi, Japan
      • Yamaguchi University Hospital
  • Yamanashi
    • Chuo-shi, Yamanashi, Japan
      • University of Yamanashi Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

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

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tirabrutinib + R-MPV in patients with newly diagnosed, treatment naïve PCNSL	Drug: Rituximab; Specified dose on specified days; Drug: Methotrexate; Specified dose on specified days; Drug: Vincristine; Specified dose on specified days; Drug: ONO-4059; Specified dose, once daily; Other Names: Tirabrutinib Hydrochloride; Drug: Procarbazine; Specified dose on specified days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tolerability evaluation	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	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		30days
Duration of response (DOR)	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 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)	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)	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

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

Study record dates

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): June 3, 2025
• Last Update Submitted That Met QC Criteria: June 1, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Reproductive Control Agents; Antimetabolites, Antineoplastic; Antimetabolites; Dermatologic Agents; Folic Acid Antagonists; Nucleic Acid Synthesis Inhibitors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Rituximab; Methotrexate; Vincristine; Procarbazine
• 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