Tirabrutinib for Central Nervous System Lymphoma
Recruiting in Palo Alto (17 mi)
+47 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Ono Pharmaceutical Co. Ltd
Must not be taking: Anticoagulants, Corticosteroids
Disqualifiers: Active infection, Severe heart, Severe lung, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Approved in 1 Jurisdiction
Trial Summary
What is the purpose of this trial?This trial is testing tirabrutinib alone and with other cancer drugs in patients with PCNSL. It targets those who haven't responded to previous treatments or are newly diagnosed. Tirabrutinib works by blocking a protein that helps cancer cells grow. Tirabrutinib was approved for use in treating primary central nervous system lymphoma.
Will I have to stop taking my current medications?
The trial requires that you stop taking certain medications before starting tirabrutinib treatment. Specifically, you must not have taken chemotherapy, certain antibody drugs, or investigational drugs within a specified period before starting the trial. Additionally, ongoing use of some corticosteroids, anticoagulants, and medications that affect liver enzymes must be stopped before participation.
What data supports the effectiveness of the drug Tirabrutinib for treating central nervous system lymphoma?
Tirabrutinib has been shown to be effective in treating relapsed or refractory primary central nervous system lymphoma, as evidenced by its approval in Japan based on phase I/II studies. In one case, a patient's brain lesions disappeared after treatment, and an autopsy confirmed no remaining tumor cells, indicating the drug's effectiveness.
12345Is tirabrutinib safe for humans?
Tirabrutinib has been studied for safety in humans, with some patients experiencing side effects like rash, vomiting, joint pain, and fatigue. Serious side effects occurred in about 41% of patients, and drug-related side effects were seen in 94% of patients in a study of those with B-cell malignancies.
12346How is the drug tirabrutinib unique in treating central nervous system lymphoma?
Tirabrutinib is unique because it is an oral drug that specifically targets and inhibits Bruton's tyrosine kinase (BTK), which is involved in the growth of certain cancer cells. This makes it a novel option for patients with central nervous system lymphoma who cannot tolerate standard treatments like high-dose methotrexate or whole-brain radiation therapy.
12345Eligibility Criteria
Adults with a confirmed diagnosis of Primary Central Nervous System Lymphoma (PCNSL) who have either not been treated before or whose disease has returned after treatment. Participants must be in good enough health, as determined by organ function tests, and have a life expectancy of at least 3 to 6 months depending on the part of the trial they're entering.Inclusion Criteria
You are expected to live for at least 6 more months.
I can take care of myself and perform daily activities.
I am 18 years old or older.
+12 more
Exclusion Criteria
I cannot swallow pills or have a condition affecting my stomach or intestines.
I do not have an active infection or have not been hospitalized for an infection requiring IV antibiotics in the last 28 days.
You have had an allergic reaction to the dye used in MRI scans.
+25 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment (Part A)
Patients with relapsed or refractory PCNSL receive tirabrutinib monotherapy
1 year
Regular visits for monitoring and assessment
Treatment (Part B)
Patients with newly diagnosed, treatment naïve PCNSL receive tirabrutinib in combination with high dose methotrexate based regimens
4 months
Regular visits for monitoring and assessment
Follow-up
Participants are monitored for safety and effectiveness after treatment
2 years
Participant Groups
The study is testing Tirabrutinib alone for those with relapsed PCNSL (Part A), and in combination with high-dose methotrexate-based regimens for newly diagnosed patients (Part B). The goal is to see how well it works and what side effects occur.
3Treatment groups
Experimental Treatment
Group I: Tirabrutinib monotherapy in patients with relapsed or refractory PCNSL (Part A)Experimental Treatment1 Intervention
Patients with relapsed or refractory PCNSL who meet eligibility criteria will be enrolled to receive tirabrutinib monotherapy.
Group II: Tirabrutinib + R-MPV in patients with newly diagnosed, treatment naïve PCNSL (Part B, Arm 2)Experimental Treatment1 Intervention
Patients with newly diagnosed treatment naïve PCNSL who meet eligibility criteria will be enrolled to receive tirabrutinib + rituximab/methotrexate/procarbazine/vincristine (R-MPV)
Group III: Tirabrutinib + MTR in patients with newly diagnosed, treatment naïve PCNSL (Part B, Arm 1)Experimental Treatment1 Intervention
Patients with newly diagnosed treatment naïve PCNSL who meet eligibility criteria will be enrolled to receive tirabrutinib + methotrexate/temozolomide/rituximab (MTR)
Tirabrutinib is already approved in Japan for the following indications:
🇯🇵 Approved in Japan as Velexbru for:
- Primary central nervous system lymphoma
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Mayo Clinic- PhoenixPhoenix, AZ
Mayo Clinic- JacksonvilleJacksonville, FL
University of Miami-Sylvester Cancer CenterMiami, FL
Orlando HealthOrlando, FL
More Trial Locations
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Who Is Running the Clinical Trial?
Ono Pharmaceutical Co. LtdLead Sponsor
References
Tirabrutinib: First Approval. [2020]Tirabrutinib (Velexbru®) is an orally administered, small molecule, Bruton's tyrosine kinase (BTK) inhibitor being developed by Ono Pharmaceutical and its licensee Gilead Sciences for the treatment of autoimmune disorders and haematological malignancies. Tirabrutinib irreversibly and covalently binds to BTK in B cells and inhibits aberrant B cell receptor signalling in B cell-related cancers and autoimmune diseases. In March 2020, oral tirabrutinib was approved in Japan for the treatment of recurrent or refractory primary central nervous system lymphoma. Tirabrutinib is also under regulatory review in Japan for the treatment of Waldenström's macroglobulinemia and lymphoplasmacytic lymphoma. Clinical development is underway in the USA, Europe and Japan for autoimmune disorders, chronic lymphocytic leukaemia, B cell lymphoma, Sjogren's syndrome, pemphigus and rheumatoid arthritis. This article summarizes the milestones in the development of tirabrutinib leading to the first approval of tirabrutinib for the treatment of recurrent or refractory primary central nervous system lymphoma in Japan.
Karnofsky Performance Status and quality of life in patients with relapsed or refractory primary CNS lymphoma from a phase I/II study of tirabrutinib. [2023]Tirabrutinib, a second-generation inhibitor of Bruton's tyrosine kinase, was approved in March 2020 for the treatment of relapsed or refractory primary central nervous system lymphoma (r/r PCNSL) based on phase I/II studies in Japan. We previously reported the overall response rate and safety profile. We describe Karnofsky Performance Status (KPS) and the quality of life (QoL) in patients with r/r PCNSL receiving tirabrutinib based on more than 1-year follow-up data.
Histological verification of the treatment effect of tirabrutinib for relapsed/refractory primary central nervous system lymphoma. [2021]Tirabrutinib (ONO/GS-4059; Ono Pharmaceutical) is a newly developed drug that selectively and irreversibly inhibits Bruton's tyrosine kinase (BTK) and has been approved in Japan for treating relapsed/refractory primary central nervous system lymphoma (PCNSL). However, its therapeutic effect is yet to be verified at the pathological level in human patients. A 64-year-old patient with recurrent PCNSL enrolled in the phase I/II clinical trial of tirabrutinib, a second-generation BTK inhibitor designed for treating relapsed/refractory PCNSL. The left cerebellum lesions on magnetic resonance imaging disappeared one month after tirabrutinib treatment. The patient died because of suspected pneumocystis pneumonia and acute exacerbation of interstitial pneumonia 43 days after starting tirabrutinib. An autopsy confirmed no viable tumor cells in the entire brain, including the left cerebellum lesion, confirming complete obliteration of tumor cells by tirabrutinib. This letter pathologically confirms the effect of tirabrutinib on relapsed/refractory PCNSL for the first time in humans.Trial registration: JapicCTI-173646. Registered 14 July 2017, https://www.clinicaltrials.jp/cti-user/trial/ShowDirect.jsp?japicId=JapicCTI-173646.
Phase I/II study of tirabrutinib, a second-generation Bruton's tyrosine kinase inhibitor, in relapsed/refractory primary central nervous system lymphoma. [2021]The safety, tolerability, efficacy, and pharmacokinetics of tirabrutinib, a second-generation, highly selective oral Bruton's tyrosine kinase inhibitor, were evaluated for relapsed/refractory primary central nervous system lymphoma (PCNSL).
Experience With Tirabrutinib in the Treatment of Primary Central Nervous System Lymphoma that Is Difficult to Treat With Standard Treatment. [2022]Standard treatment options for primary central nervous system lymphoma (PCNSL) include high-dose methotrexate (HD-MTX)-based drug therapy and whole-brain radiation therapy. However, there are many cases in which these standard treatment options are not tolerated for various reasons. In the present study, five cases of refractory/relapsed PCNSL that are difficult to treat with standard treatment were successfully treated by tirabrutinib.
Long-term safety profile of tirabrutinib: final results of a Japanese Phase I study in patients with relapsed or refractory B-cell malignancies. [2023]Tirabrutinib is a Bruton's tyrosine kinase inhibitor for treating B-cell malignancies. We report the final results of a Phase I study of tirabrutinib in 17 Japanese patients with B-cell malignancies. Patients were administered tirabrutinib at a dose of 160 mg, 320 mg, or 480 mg once daily, or 300 mg twice daily (N = 3, 3, 4, and 7, respectively). Three patients continued tirabrutinib until study completion (November 30, 2020). Adverse events (AEs) occurred in all 17 patients, with Grade 3-4 AEs in 8 (47.1%), serious AEs in 7 (41.2%), drug-related AEs in 16 (94.1%), and Grade 3-4 drug-related AEs in 6 (35.3%). Drug-related AEs reported in 3 or more patients were rash, vomiting, neutropenia, arthralgia, and malaise. One additional serious AE (benign neoplasm of the lung, unrelated to tirabrutinib) occurred after the previous data cutoff (January 4, 2018). Tirabrutinib administration and response assessment were continued for over 4 years in 4 patients. The overall response rate was 76.5% (13/17 patients). The median (range) time to response and duration of response were 0.9 (0.9-5.9) months and 2.59 (0.08-5.45) years, respectively. These findings demonstrate the long-term safety and efficacy of tirabrutinib in Japanese patients with B-cell malignancies.Clinical trial registration: JapicCTI-142682 ( http://www.clinicaltrials.jp/ ).