Summary

Eligibility
for people ages 18 years and up (full criteria)
Location
at Irvine, California and other locations
Dates
study started
estimated completion
Principal Investigator
by Daniela Bota

Description

Summary

This study will evaluate the efficacy, safety, and pharmacokinetics of tirabrutinib monotherapy in patients with relapsed or refractory PCNSL (Part A), and tirabrutinib in combination with one of two different high dose methotrexate based regimens (methotrexate/ temozolimide/rituximab or rituximab/methotrexate/procarbazine/ vincristine) as first line therapy in patients with newly diagnosed, treatment naïve PCNSL (Part B)

Official Title

An Open-label Phase II Study to Investigate the Efficacy, Safety, and Pharmacokinetics of Tirabrutinib in Patients With Primary Central Nervous System Lymphoma (PCNSL)

Keywords

Part A: Relapsed or Refractory Primary Central Nervous System Lymphoma (PCNSL), Part B: Newly Diagnosed, Treatment naïve PCNSL, Bruton's Tyrosine Kinase (BTK) Inhibitor, tirabrutinib, ONO-4059, PROSPECT, relapsed, refractory, first line, Lymphoma, Tirabrutinib

Eligibility

You can join if…

Open to people ages 18 years and up

(Part A)

  1. Written informed consent by the patient prior to screening
  2. Patients aged ≥ 18 years on the day of consenting to the study
  3. Pathologic diagnosis of PCNSL
  4. Relapse or refractory PCNSL with at least one prior HD MTX based therapy for PCNSL
  5. Measurable brain lesion with a minimum diameter > 1.0 cm in gadolinium enhanced magnetic resonance imaging (MRI) performed within 14 days before starting tirabrutinib treatment
  6. ECOG PS of 0, 1 or 2
  7. Life expectancy of at least 3 months
  8. Adequate bone marrow, renal, and hepatic function

Inclusion Criteria (Part B)

  1. Written informed consent by the patient prior to screening
  2. Patients aged ≥ 18 years on the day of consenting to the study
  3. Pathologic diagnosis of PCNSL within the past 3 months
  4. No prior anti-tumor treatments for PCNSL
  5. Patients who, in the opinion of the Investigator, are suitable to receive treatment with a high dose methotrexate containing regimen
  6. Measurable brain lesion with a minimum diameter > 1.0 cm in gadolinium enhanced MRI performed within 14 days before starting study treatment
  7. ECOG PS of 0, 1 or 2
  8. Life expectancy of at least 6 months
  9. Adequate bone marrow, renal, and hepatic function

You CAN'T join if...

(Part A)

  1. Intraocular PCNSL with no brain lesion
  2. Patient who is intolerant of contrast enhanced MRI due to allergic reactions to contrast agents
  3. Patient with non-B cell PCNSL
  4. Patient with systemic presence of lymphoma
  5. Prior chemotherapy within 21 days, nitrosourea within 42 days, an antibody drug with anticancer activity (e.g., rituximab) within 28 days, prior radiotherapy within 14 days, prior major invasive surgery within 28 days, or allogeneic stem cell transplant within 6 months before starting tirabrutinib treatment
  6. Prior BTK inhibitor treatment
  7. Prior investigational drugs (including treatment in clinical research, unapproved combination products, and new dosage forms) within 28 days or 5 half-lives, whichever is shorter, before starting tirabrutinib treatment
  8. Concomitant systemic corticosteroid on an ongoing basis within 14 days before starting tirabrutinib treatment, with the exception of the following:
  9. Equivalent of up to 10 mg/day of prednisone for a disease other than PCNSL
  10. Equivalent of up to 50 mg/day of prednisone (equal to 8 mg/day of dexamethasone) for patients with lesions of the brain or spinal cord or both
  11. Patient who has received a CYP3A4 inducer or P-gp inducer within 14 days before starting tirabrutinib treatment
  12. . Concomitant warfarin, any other warfarin derivative anticoagulant, vitamin K antagonists, novel oral anticoagulants, or antiplatelet therapy on an ongoing basis within 7 days before starting tirabrutinib treatment
  13. . Active malignancy, other than PCNSL requiring systemic therapy
  14. . Poorly controlled comorbidity, severe heart, severe lung disease, clinically significant liver diseases that could affect protocol compliance or safety or efficacy assessments
  15. . Patient with bleeding diathesis
  16. . Patients with a history of moderate or severe hepatic impairment
  17. . QTcF > 480 milliseconds or requirement for ongoing treatment with concomitant medications that prolong the QT interval
  18. . 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
  19. . Prior history of hypersensitivity or anaphylaxis to tirabrutinib
  20. . Prior history of Stevens Johnson Syndrome or Toxic Epidermal Necrolysis
  21. . Medical history of organ allografts
  22. . Tests positive for HIV-1 antibody and HIV-2 antibody, human T-lymphotropic virus 1 antibody, HBs antigen, or HCV antibody. Tests positive for HBs antibody or hepatitis B virus core protein antibody and has a result of at least detectable in a hepatitis B virus deoxyribonucleic acid assay despite testing negative for HBs antigen.
  23. . 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.
  24. . Women who are pregnant or lactating
  25. . Patient is found incapable of giving consent due to dementia or another such condition
  26. . Patient is found to be otherwise ineligible for the study by the Investigator or sub-Investigator.

Exclusion Criteria (Part B)

  1. Intraocular PCNSL with no brain lesion
  2. Patients for whom the selected backbone regimen medications (i.e, methotrexate/temozolomide/rituximab for MTR and rituximab/methotrexate/procarbazine/vincristine for R-MPV) are contraindicated
  3. Patients with a history of intolerable toxicity, hypersensitivity, anaphylaxis to the selected backbone regimen medications
  4. Patient who is intolerant of contrast enhanced MRI due to allergic reactions to contrast agents
  5. Patient with non-B cell PCNSL
  6. Patient with systemic presence of lymphoma
  7. Prior chemotherapy within 21 days, nitrosourea within 42 days, an antibody drug with anticancer activity (e.g., rituximab) within 28 days, prior radiotherapy within 14 days, prior major invasive surgery within 28 days, or allogeneic stem cell transplant within 6 months before starting tirabrutinib treatment
  8. Prior BTK inhibitor treatment
  9. Prior investigational drugs (including treatment in clinical research, unapproved combination products, and new dosage forms) within 28 days or 5 half-lives, whichever is shorter, before starting tirabrutinib treatment
  10. . Concomitant systemic corticosteroid on an ongoing basis within 14 days before starting tirabrutinib treatment, with the exception of the following:
  11. Equivalent of up to 10 mg/day of prednisone for a disease other than PCNSL
  12. Equivalent of up to 50 mg/day of prednisone (equal to 8 mg/day of dexamethasone) for patients with lesions of the brain or spinal cord or both
  13. . Patient who has received a CYP3A4 inducer or P-gp inducer within 14 days before starting tirabrutinib treatment
  14. . Concomitant warfarin, any other warfarin derivative anticoagulant, vitamin K antagonists, novel oral anticoagulants, or antiplatelet therapy on an ongoing basis within 7 days before starting tirabrutinib treatment
  15. . Active malignancy, other than PCNSL requiring systemic therapy
  16. . Poorly controlled comorbidity, severe heart, severe lung disease, clinically significant liver diseases that could affect protocol compliance or safety or efficacy assessments
  17. . Patient with bleeding diathesis
  18. . Patients with a history of moderate or severe hepatic impairment
  19. . QTcF > 480 milliseconds or requirement for ongoing treatment with concomitant medications that prolong the QT interval
  20. . 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
  21. . Prior history of hypersensitivity or anaphylaxis to tirabrutinib
  22. . Prior history of Stevens Johnson Syndrome or Toxic Epidermal Necrolysis
  23. . Medical history of organ allografts
  24. . Tests positive for HIV-1 antibody and HIV-2 antibody, human T-lymphotropic virus 1 antibody, HBs antigen, or HCV antibody. Tests positive for HBs antibody or hepatitis B virus core protein antibody and has a result of at least detectable in a hepatitis B virus deoxyribonucleic acid assay despite testing negative for HBs antigen.
  25. . 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.
  26. . Women who are pregnant or lactating
  27. . Patient is found incapable of giving consent due to dementia or another such condition
  28. . Patient is found to be otherwise ineligible for the study by the Investigator or sub-Investigator.

Locations

  • University of California, Irvine accepting new patients
    Irvine California 92868 United States
  • City of Hope Comprehensive Breast Cancer Center not yet accepting patients
    Duarte California 91010 United States

Lead Scientist at UC Irvine

  • Daniela Bota
    Professor, Neurology, School of Medicine. Authored (or co-authored) 82 research publications

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Ono Pharmaceutical Co. Ltd
Links
Related Info
ID
NCT04947319
Phase
Phase 2 Lymphoma Research Study
Study Type
Interventional
Participants
Expecting 112 study participants
Last Updated