What side effects are associated with this type of intervention?

Common treatments for Central Nervous System Lymphoma (PCNSL) include high-dose methotrexate-based regimens, often combined with other agents like temozolomide, rituximab, procarbazine, and vincristine. Known side effects of these treatments can include hematologic toxicity (e.g., neutropenia, anemia), gastrointestinal issues (e.g., nausea, vomiting, diarrhea), neurotoxicity, and increased risk of infections. For Bruton's Tyrosine Kinase Inhibitors like Tirabrutinib, side effects may include fatigue, diarrhea, and increased risk of infections. Patients should discuss these potential side effects with their healthcare provider to make informed treatment decisions.

What prior FDA approvals exist?

The FDA has approved several treatments for Central Nervous System Lymphoma (PCNSL), including high-dose methotrexate-based regimens, which are often combined with other agents like temozolomide and rituximab. While specific FDA approvals for BTK inhibitors like Tirabrutinib in PCNSL are not detailed, similar drugs such as ibrutinib have shown promise in treating other types of lymphomas. These treatments aim to target specific pathways involved in cancer cell proliferation and survival, offering a more targeted approach compared to traditional chemotherapy.

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Bruton's Tyrosine Kinase (BTK) Inhibitor

Tirabrutinib for Central Nervous System Lymphoma

Q: What other types of research exist?

Promising alternatives to Tirabrutinib for CNS lymphoma patients include high-dose methotrexate-based regimens combined with other agents such as temozolomide, rituximab, procarbazine, and vincristine. Additionally, novel agents like moxetumomab pasudotox and BRAF inhibitors (e.g., vemurafenib) have shown potential in treating resistant or relapsed CNS lymphomas.

Phase 2

Recruiting

Research Sponsored by Ono Pharmaceutical Co. Ltd

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

ECOG PS of 0, 1 or 2

Patients aged ≥ 18 years on the day of consenting to the study

Must not have

Patient is unable to swallow tablets; has malabsorption, malabsorption syndrome, or a comorbidity that affects gastric function; has undergone complete resection of the stomach or small intestine; has ulcerative colitis or symptomatic inflammatory bowel disease; or has partial or complete intestinal obstruction.

Active infection, including a HIV, cytomegalovirus infection or SARS-CoV-2, or has had, within 28 days before starting tirabrutinib treatment, an infection (other than nail trichophytosis) that requires hospitalization or an intravenous antibiotic

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 2 years

Awards & highlights

No Placebo-Only Group

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Possible side effects include reactions related to immune system activation, liver issues, bleeding problems due to blood thinners interaction, infections risk increase including HIV or hepatitis reactivation if previously infected. Specific side effects from tirabrutinib are not listed but may resemble other drugs in its class.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I can take care of myself and perform daily activities.

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I am 18 years old or older.

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I have a brain lesion larger than 1 cm, confirmed by a recent MRI.

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I have not received any treatment for my brain lymphoma.

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I have been diagnosed with primary central nervous system lymphoma.

Select...

My brain lymphoma has returned or didn't respond to treatment with high-dose methotrexate.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I cannot swallow pills or have a condition affecting my stomach or intestines.

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I do not have an active infection or have not been hospitalized for an infection requiring IV antibiotics in the last 28 days.

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I have had an organ transplant.

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I have been treated with a BTK inhibitor before.

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I am unable to give consent due to a condition like dementia.

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My lymphoma has spread throughout my body.

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I am not pregnant or breastfeeding.

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I haven't taken any experimental drugs within the last 28 days or 5 half-lives, whichever is shorter.

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I have another cancer besides PCNSL that needs treatment.

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My cancer is in the eye and has not spread to the brain.

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The medications methotrexate, temozolomide, rituximab, procarbazine, and vincristine are not safe for me.

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My heart's electrical cycle is longer than normal or I'm on medication that affects it.

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I do not have severe heart, lung, or liver diseases that could affect my treatment.

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I have tested positive for HIV, HTLV-1, hepatitis B, or hepatitis C.

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I have had moderate to severe liver problems.

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I am taking up to 10 mg/day of prednisone for a condition that is not brain lymphoma.

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I haven't had certain cancer treatments or major surgery within specific time frames before starting tirabrutinib.

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I am taking up to 50 mg/day of prednisone for brain or spinal cord lesions.

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I have a bleeding disorder.

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My cancer is a non-B cell type of primary central nervous system lymphoma.

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I haven't taken blood thinners or antiplatelet drugs in the last 7 days.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and 2 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Complete response rate (CRR) (Part B)

Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) during induction (Part B)

Overall response rate (ORR) (Part A)

+1 more

Secondary study objectives

Best overall response (BOR) (Part A and B)

Change in corticosteroid dose (Part A)

Duration of response (DOR) (Part A and B)

+4 more

Side effects data

From 2019 Phase 2 trial • 152 Patients • NCT03100942

11%

Fatigue

11%

Upper respiratory tract infection

11%

Alanine aminotransferase increased

11%

Aspartate aminotransferase increased

11%

Arthralgia

11%

Rash

Pyrexia

Diarrhoea

Gastroenteritis viral

Nasopharyngitis

Dizziness

Sinusitis

Nausea

Vomiting

Neutropenia

Lymphadenopathy

Bronchitis

Dental caries

Laryngitis

Lower respiratory tract infection

Oral herpes

Myalgia

Pruritus generalised

Insomnia

Fall

Anaemia

Pancreatitis acute

Suicidal ideation

Acute coronary syndrome

Seasonal allergy

Influenza

Furuncle

Urinary tract infection

Back pain

Musculoskeletal pain

Osteoarthritis

Rheumatoid arthritis

Migraine

Hyperhidrosis

Rash papular

Rash pruritic

100%

80%

60%

40%

20%

Study treatment Arm

Lanraplenib

Filgotinib

Placebo to Lanraplenib

Placebo to Filgotinib

Placebo to Tirabrutinib

Placebo on Placebo Controlled Period

Tirabrutinib

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

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)

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Tirabrutinib

2012

Completed Phase 2

~390

0 / 27Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for Central Nervous System Lymphoma (CNSL) include Bruton's Tyrosine Kinase (BTK) inhibitors like Tirabrutinib, which block the BTK enzyme essential for B-cell growth and survival, thereby disrupting cancer cell proliferation. High-dose methotrexate-based regimens are also used, which inhibit DNA synthesis, leading to cell death. These treatments are crucial for CNSL patients as they effectively target cancer cells within the central nervous system, overcoming the limitations posed by the blood-brain barrier.

Find a Location

Who is running the clinical trial?

Ono Pharmaceutical Co. LtdLead Sponsor

171 Previous Clinical Trials

95,624 Total Patients Enrolled

Arata AoiStudy DirectorOno Pharma USA Inc

Project LeaderStudy DirectorOno Pharma USA Inc

25 Previous Clinical Trials

3,301 Total Patients Enrolled

Media Library

Tirabrutinib (Bruton's Tyrosine Kinase (BTK) Inhibitor) Clinical Trial Eligibility Overview. Trial Name: NCT04947319 — Phase 2

$Central Nervous System Lymphoma Research Study Groups: Tirabrutinib monotherapy in patients with relapsed or refractory PCNSL (Part A), Tirabrutinib + MTR in patients with newly diagnosed, treatment naïve PCNSL (Part B, Arm 1), Tirabrutinib + R-MPV in patients with newly diagnosed, treatment naïve PCNSL (Part B, Arm 2)$