Relapsed and refractory primary CNS lymphoma Cancer
Conditions
Interventions
This is a prospective, multicentre, sequential single-arm phase II study for zanubrutinib for the treatment of RR-PCNSL.
Patients and legal representatives who consent to participate will have a scre
Sponsors
University of Birmingham
Eligibility
Sex/Gender
All
Age
16 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Aged =16 years of age 2. Histologically confirmed CD20+ diffuse large B cell lymphoma (DLBCL) confined to the CNS 3. Relapsed or refractory PCNSL (defined as disease progression following complete response (CR)/unconfirmed complete response (CRu)/partial response (PR), or failure to achieve PR after one or more lines of therapy; one therapy line must have included at least 1 cycle of high-dose methotrexate [=1 g/m²]) 4. Measurable disease on contrast-enhanced MRI of brain (and/or spinal cord) 5. ECOG performance status of 0 to 2, or 3 if attributed to lymphoma 6. Ability to swallow capsules 7. Adequate renal and liver function defined as: 7.1. Creatinine clearance =30 ml/min (as estimated by the Cockcroft-Gault equation or as measured by nuclear medicine scan or 24-hour urine collection) 7.2. Serum total bilirubin 50 x10e9/l, neutrophils >1 x10e9/l, haemoglobin >80 g/l 9. Patient willing and able to comply with scheduled visits, treatment plan, investigations and other study procedures 10. Written informed consent for the trial
Exclusion criteria
Exclusion criteria: 1. Current evidence or prior history of systemic lymphoma 2. Exclusive intraocular involvement 3. Active infection requiring intravenous antimicrobials 4. Chemotherapy for lymphoma within 2 weeks of the first dose of zanubrutinib 5. Whole-brain radiotherapy within 4 weeks of the first dose of zanubrutinib 6. Contra-indication to lumbar puncture 7. Prior exposure to BTK inhibitor 8. Known bleeding disorder e.g haemophilia or severe Von-Willebrand Disease 9. Current use of warfarin, or dual anti-platelet therapy. Therapeutic anticoagulation with direct oral anticoagulants or low molecular weight heparin is permitted 10. Evidence of active HIV, HBV or HCV infection, except: 10.1. HIV-positive patients established on anti-retroviral treatment, with undetectable HIV RNA, after discussion with the patient’s HIV physician 10.2. HBV core antibody-positive patients who are (i) surface antigen-negative and (ii) HBV DNA PCR negative, who take prophylaxis as per institutional guidelines 11. Patients who are pregnant or breastfeeding (women of childbearing potential must have a negative urine or serum pregnancy test prior to trial entry) 12. Patients and patients with partners of childbearing potential (pre-menopausal female capable of becoming pregnant) not willing to use highly effective contraception (see Section 9.6) during and for 12 months after cessation of therapy 13. Clinically significant cardiac or respiratory dysfunction that, in the opinion of the investigator, would jeopardise the safety of the patient in the trial 14. Active malignancy treated in the last 2 years, except: 14.1. Non-melanoma skin cancer 14.2. Carcinoma in situ of the cervix or breast 14.3. Incidental finding of prostate cancer (T1a or T1b)
Design outcomes
Secondary
| Measure | Time frame |
|---|---|
| Patients will be followed up for 1 year: 1. Complete response at response assessment by MRI scan after two cycles of treatment, response assessed locally or by central MRI scan review 2. Overall response assessed by MRI scan after two cycles of treatment, assessment by central MRI review 3. Best overall response assessed by MRI scan within 12 months of registration, response assessed locally or by central MRI scan review 4. Progression-free survival, defined as the time from trial entry to the date of progressive disease or death from any cause 5. Overall survival, defined as the time from trial entry to the date of death from any cause 6. Event-free survival, defined as the time from trial entry to the first of initiation of a new anti-lymphoma treatment, progressive disease, or death from any cause 7. Toxicity, defined as the proportion of patients experiencing one or more: grade 2 or higher non-haematological adverse events (AE), grade 3 or higher haematological AE, or any serious AE (SAE) | — |
Primary
| Measure | Time frame |
|---|---|
| Overall response (complete response [CR] + unconfirmed CR [CRu] + partial response [PR]) after two cycles of treatment, assessed locally using international consensus criteria (Abrey et al., 2005). Patients will be followed up for 1 year. | — |
Countries
England, Northern Ireland, Scotland, United Kingdom, Wales
Outcome results
None listed