Tirabrutinib for Central Nervous System Lymphoma

Recruiting at 45 trial locations

Overseen By International Clinical Trial Support Desk

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Ono Pharmaceutical Co. Ltd

Must not be taking: Anticoagulants, Corticosteroids

Disqualifiers: Active infection, Severe heart, Severe lung, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

112 Participants Needed

What You Need to Know Before You Apply

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.

Is 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. ^{1 2 3 4 5}

How 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. ^{1 2 4 5 6}

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. ^{1 2 4 5 6}

Who Is on the Research Team?

Project Leader

Principal Investigator

Ono Pharmaceutical Co. Ltd

Are You a Good Fit for This Trial?

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.

You need to sign a paper saying you agree to participate before you can be checked for eligibility.

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Tirabrutinib

Trial Overview 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.

How Is the Trial Designed?

Group I: Tirabrutinib monotherapy in patients with relapsed or refractory PCNSL (Part A) Experimental Treatment 1 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 Treatment 1 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 Treatment 1 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

Who Is Running the Clinical Trial?

Ono Pharmaceutical Co. Ltd

Lead Sponsor

Trials

182

Recruited

97,100+

Shinji Takai

Ono Pharmaceutical Co. Ltd

Chief Medical Officer since 2023

MD from an unspecified institution

Gyo Sagara

Ono Pharmaceutical Co. Ltd

Chief Executive Officer since 2024

PhD in Pharmaceutical Sciences from Kyoto University

Published Research Related to This Trial

Tirabrutinib is an oral BTK inhibitor that irreversibly binds to Bruton's tyrosine kinase in B cells, effectively blocking harmful B cell receptor signaling associated with certain cancers and autoimmune disorders.

In March 2020, tirabrutinib received approval in Japan for treating recurrent or refractory primary central nervous system lymphoma, and it is currently under review for other conditions like Waldenström's macroglobulinemia and lymphoplasmacytic lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tirabrutinib: First Approval. Dhillon, S.[2020]

Tirabrutinib, a second-generation Bruton's tyrosine kinase inhibitor, has been shown to maintain Karnofsky Performance Status (KPS) and improve quality of life (QoL) in patients with relapsed or refractory primary central nervous system lymphoma (r/r PCNSL) over a median follow-up of 14.9 months.

Patients experienced significant improvements in global health status and emotional functioning, indicating that tirabrutinib not only helps manage the disease but also enhances the overall well-being of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Karnofsky Performance Status and quality of life in patients with relapsed or refractory primary CNS lymphoma from a phase I/II study of tirabrutinib. Arakawa, Y., Narita, Y., Nagane, M., et al.[2023]

Tirabrutinib, a selective BTK inhibitor, demonstrated a complete obliteration of tumor cells in a 64-year-old patient with relapsed/refractory primary central nervous system lymphoma (PCNSL), as confirmed by autopsy after one month of treatment.

This case represents the first pathological confirmation of tirabrutinib's efficacy in humans for treating PCNSL, although the patient later died from complications unrelated to the drug.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Histological verification of the treatment effect of tirabrutinib for relapsed/refractory primary central nervous system lymphoma. Okita, Y., Kano-Fujiwara, R., Nakatsuka, SI., et al.[2021]

Tirabrutinib, a selective Bruton's tyrosine kinase inhibitor, showed a favorable efficacy in treating relapsed/refractory primary central nervous system lymphoma (PCNSL), with an overall response rate of 64% across 44 patients in the study.

No dose-limiting toxicities were observed at the maximum tested dose of 480 mg, indicating a good safety profile, although some patients experienced serious adverse events like neutropenia and pneumonia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I/II study of tirabrutinib, a second-generation Bruton's tyrosine kinase inhibitor, in relapsed/refractory primary central nervous system lymphoma. Narita, Y., Nagane, M., Mishima, K., et al.[2021]

In a study of 5 patients with refractory or relapsed primary central nervous system lymphoma (PCNSL), tirabrutinib demonstrated a 100% response rate, indicating its potential as an effective treatment for those who cannot tolerate standard therapies.

Despite some manageable adverse reactions, tirabrutinib was well-tolerated, and the median survival for patients was 8 months, suggesting it could be a promising alternative for improving outcomes in difficult-to-treat PCNSL cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Experience With Tirabrutinib in the Treatment of Primary Central Nervous System Lymphoma that Is Difficult to Treat With Standard Treatment. Yoshioka, H., Okuda, T., Nakao, T., et al.[2022]

In a Phase I study involving 17 Japanese patients with B-cell malignancies, tirabrutinib demonstrated a high overall response rate of 76.5%, indicating its efficacy as a treatment option.

While adverse events were common, with 94.1% of patients experiencing drug-related side effects, the long-term safety profile was acceptable, with some patients continuing treatment for over 4 years.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term safety profile of tirabrutinib: final results of a Japanese Phase I study in patients with relapsed or refractory B-cell malignancies. Munakata, W., Ando, K., Yokoyama, M., et al.[2023]

Citations

1. New Zealand pubmed.ncbi.nlm.nih.gov

Tirabrutinib: First Approval. [2020]

2. England pubmed.ncbi.nlm.nih.gov

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]

3. England pubmed.ncbi.nlm.nih.gov

Histological verification of the treatment effect of tirabrutinib for relapsed/refractory primary central nervous system lymphoma. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Phase I/II study of tirabrutinib, a second-generation Bruton's tyrosine kinase inhibitor, in relapsed/refractory primary central nervous system lymphoma. [2021]

5. Greece pubmed.ncbi.nlm.nih.gov

Experience With Tirabrutinib in the Treatment of Primary Central Nervous System Lymphoma that Is Difficult to Treat With Standard Treatment. [2022]

6. Japan pubmed.ncbi.nlm.nih.gov

Long-term safety profile of tirabrutinib: final results of a Japanese Phase I study in patients with relapsed or refractory B-cell malignancies. [2023]