Explore a Clinical Trial for Your Patients Living with PCNSL

About IGNITE

This study is evaluating tirabrutinib monotherapy versus rituximab-temozolomide (R-TMZ) combination therapy in adult participants with relapsed or refractory PCNSL. About 130 participants will be enrolled globally and randomized to receive tirabrutinib or R-TMZ in a 2:1 ratio.

Currently, there is no drug therapy specifically approved to treat PCNSL in the US or Europe. The treatments that are used instead may be effective at first, but many individuals experience challenging side effects, and the disease progresses to relapsed or refractory status.

Study Design

The length of participation in IGNITE will be different for each person. Throughout the study, participants will be closely monitored and will visit the research site regularly for assessments, procedures, and health checks. The number of cycles will vary per person, depending on what study drug is assigned and how they respond.

The study is made up of the following 3 periods:

About the Study Drug

IGNITE is being conducted to research an investigational study drug called tirabrutinib. It is a second-generation, highly selective, covalent, irreversible oral inhibitor of BTK. Tirabrutinib is taken once a day as an oral tablet.

In this study, tirabrutinib is being compared to a standard PCNSL study drug called R-TMZ, a combination therapy of rituximab (intravenous [IV] infusion) and temozolomide (oral capsule).

Tirabrutinib has not been approved in the US or Europe for use to treat PCNSL outside of clinical research.

No Cost for Patients to Participate in the Clinical Study

All participants in this study will receive either the investigational study drug or the standard study drug at no cost. Reimbursement for study-related travel expenses may be available.

Eligibility Criteria

Key Inclusion Criteria

Eligible participants must:

• Be aged ≥ 18 years on the day of consenting to the study
• Have a pathology report confirming diagnosis of B-cell PCNSL
• Have relapsed or refractory B-cell PCNSL with at least 1 prior HD-MTX–based therapy for PCNSL
  • Relapsed disease: Patients who achieved a response to the last treatment and subsequently experienced disease progression
  • Refractory disease: Patients whose best response to the last treatment was stable disease or PD
• Have a life expectancy of at least 3 months
• Have 1 or more bi-dimensionally measurable brain lesions with a minimum diameter ≥ 1 cm × ≥ 1 cm in gadolinium-enhanced MRI based on local read performed within 14 days before starting study drug
• Have adequate bone marrow, renal, and hepatic function

Key Exclusion Criteria

Eligible participants must NOT:

• Have isolated intraocular or spinal PCNSL without brain lesions
• Have non–B-cell PCNSL or systemic lymphoma
• Have contraindication to MRI or contrast use
• Have prior therapies within the following periods before starting the study drug:
  • Nitrosoureas ≤ 42 days
  • Cytarabine or other cytotoxics (except procarbazine, methotrexate) ≤ 28 days
  • Procarbazine ≤ 21 days; methotrexate ≤ 14 days
  • Investigational non-cytotoxics ≤ 14 days or 5 half-lives
  • Investigational cytotoxics ≤ 28 days or 5 half-lives
  • Autologous stem cell transplant (ASCT) or CAR-T cell therapy ≤ 1 month; allo-SCT ≤ 6 months
• Have not been refractory to temozolomide with or without rituximab containing regimens in the last PCNSL treatment
• Have active malignancy, other than PCNSL, requiring systemic therapy
  • Participants with a history of non-melanoma skin cancer, low-grade cervical/prostate cancer that does not require systemic therapy and is not progressing, and breast/prostate cancer treated with curative intent therapy and on hormonal maintenance therapy can be enrolled.

Additional inclusion and exclusion criteria may apply.

Refer a Patient

If you have a patient who you think may qualify, please refer your patient to IGNITEClinicalTrial.com to take the prescreening questionnaire to determine their eligibility.