BICICL: BTK and Immune Checkpoint Inhibitor in Central Nervous System (CNS) Lymphoma

Phase 1

• Conditions: Central Nervous System Lymphoma; Cancer - Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma

• Registration Number: ACTRN12622000547741
• Lead Sponsor: Monash University

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2022-04-07
• Last Update Posted: 13 March 2023

Recruitment & Eligibility

• Status: ot yet recruiting
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

Histologically proven aggressive B cell CNS lymphoma including diffuse large B cell lymphoma (DLBCL), mantle cell lymphoma (MCL) or high-grade transformation of chronic lymphocytic leukaemia (CLL) or indolent lymphoma with:
Disease progression after PR or CR to the most recent therapy
Refractory to most recent therapy (failure to achieve PR or CR)
Treatment-naïve patients unsuitable for cytotoxic chemotherapy (maximum of 10 patients)
No active extra-CNS disease (apart from CLL not requiring therapy or a monoclonal B cell lymphocytosis)
ECOG performance status 0-2 and higher if activity is limited due to neurological deficit
No evidence of active infection or autoimmune disease
Not requiring corticosteroids >10mg prednisolone/day or equivalent except short term for acute management of CNS disease
No therapy with either BTK or PD1/PD-L1 inhibitor within the previous 6 months
Patients who are post-allogeneic stem cell transplant or chimeric antigen receptor (CAR)-T cell therapy will be eligible.

Exclusion Criteria

CNS lymphoma of a histological type other than that specified in Inclusion criteria. e.g., low-grade lymphoma, T-cell lymphoma etc.
Presence of lymphoma outside the CNS, i.e., systemic lymphoma, apart from CLL not requiring treatment or a monoclonal B cell lymphocytosis
Treatment with a BTK inhibitor and/or an immune checkpoint inhibitor within the 6 months prior to study entry.
Require corticosteroid therapy for management of CNS lymphoma at a dose more than 16 mg dexamethasone daily or equivalent
Corticosteroid therapy of more than 16 mg dexamethasone daily or equivalent at study entry from which, in the Investigator’s opinion, it is expected that the subject cannot be tapered off after the first 4 weeks of study treatment.
Intraocular primary CNS lymphoma without evidence of brain disease
Secondary CNS lymphoma actively receiving treatment for extra-CNS disease
Primary CNS lymphoma actively receiving concomitant local or systemic therapy for CNS disease
Active autoimmune diseases or history of autoimmune diseases that may relapse.
Any active malignancy within 2 years before first dose of study drug except for the specific cancer under investigation in this study and any locally recurring cancer that has been treated curatively (e.g., resected basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix or breast)
Any condition, apart from the disease under examination, that required systemic treatment with either corticosteroids (more than 10 mg daily of prednisone or equivalent) or other immunosuppressive medication within 14 days before first dose of study drug. If dexamethasone is being administered for CNS lymphoma, prednisone or equivalents should not be given concurrently.
Uncontrolled diabetes or Grade 1 or higher laboratory test abnormalities in potassium, sodium, or corrected calcium despite standard medical management or Grade 3 or higher hypoalbuminemia within 14 days before first dose of study drug
History of interstitial lung disease, non-infectious pneumonitis or uncontrolled diseases including pulmonary fibrosis, acute lung diseases, etc.
Severe chronic or active infections requiring systemic antibacterial, antifungal or antiviral therapy, including tuberculosis infection, etc
Human immunodeficiency virus (HIV) infection, or active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] detected)
Any major surgical procedure requiring general anaesthesia within 28 days before first dose of study drug apart from that required to obtain a tissue biopsy.
Prior organ transplantation
Any of the following cardiovascular risk factors: Cardiac chest pain, defined as moderate pain that limits instrumental activities of daily living, within 28 days before first dose of study drug; Pulmonary embolism within 28 days before first dose of study drug; Any history of acute myocardial infarction within 6 months before first dose of study drug; Any history of heart failure meeting New York Heart Association (NYHA) Classification III or IV within 6 months before first dose of study drug; Any event of ventricular arrhythmia of Grade 2 or higher in severity within 6 months before first dose of study drug; Any history of cerebrovascular accident within 6 months before first dose of study drug; Uncontrolled hypertension: systolic pressure more than 160 mmHg or diastolic pressure more than 100 mmHg despite

Study & Design

• Study Type: Interventional
• Study Design: Not specified