This study is being conducted to evaluate the safety and efficacy of the combination of pemetrexed and zanubrutinib (called induction therapy) followed by zanubrutinib treatment alone (also called maintenance therapy) in people who have relapsed or refractory (RR) primary central nervous system lymphoma (PCNSL) or isolated central nervous system relapse of B cell lymphoma (SCNSL). Assessments include how well people respond to this treatment, whether their disease gets better or worse, and their survival. Safety of this treatment and its side effects also will be assessed.
Primary CNS lymphoma or isolated secondary CNS involvement by diffuse large B cell lymphoma with measurable disease
Cytologic diagnosis of B cell non-Hodgkin's lymphoma with measurable disease
Ocular lymphoma with histologic confirmation of ocular lymphoma and measurable intracranial tumor. Slit-lamp examination and vitreal or retinal biopsy will be done to confirm ocular lymphoma.
Karnofsky performance status (KPS) ≥ 30% (≥ 50% for patients ≥ 60 years-old)
Serious uncontrolled concurrent illness or comorbid condition
Other active systemic malignancy except for basal cell carcinoma of the skin, cervical carcinoma in situ or very low and low risk prostate cancer under observation. Patients with a remote history (3 years or more) of malignancy are eligible for the protocol in the absence of active disease
Concurrent chronic systemic immune therapy, targeted therapy not indicated in this study protocol
Unable to comprehend the study requirements or who are not likely to comply with the study protocol
Single group
Pemetrexed
DrugParticipants will receive 900 mg/m\^2 via IV infusion over 10 minutes every 3 weeks x 4-8 induction cycles (21 days per cycle) as part of the induction therapy.
Zanubrutinib
DrugParticipants will receive 320 mg PO daily or dose-adjusted when given concomitantly with CYP3A4 inhibitor on Days 3-19 of each induction cycle x 4-8 cycles (21 days per cycle) as part of the induction therapy. For those on maintenance therapy, participants will receive 320 mg PO daily or dose-adjusted when given concomitantly with CYP3A4 inhibitor on Days 1-28 of each maintenance cycle (28 days per cycle) until the transplant (if applicable) or disease progression.
Autologous Stem Cell Transplant (ASCT)
Procedure/SurgeryASCT will occur in participants who are candidates for this procedure according to standard of care institutional protocols
Whole Brain Radiation Therapy (WBRT)
RadiationWBRT will occur in participants who are candidates for this procedure but not candidates for ASCT according to standard of care institutional protocols
Best Overall Response Rate (ORR) to Induction Therapy
Best ORR to induction therapy is defined as the best response between the start of induction therapy until the end of induction therapy based on the criteria set forth in "Report of an international workshop to standardize baseline evaluation and response criteria for primary CNS lymphoma" (2005).
Best Overall Response Rate (ORR) after transplant, WBRT + zanubrutinib maintenance, or zanubrutinib maintenance alone
Best ORR is defined as the best response between the transplant and end of study, WBRT and end of study, or start of maintenance therapy and end of study. Response is based on the criteria set forth in "Report of an international workshop to standardize baseline evaluation and response criteria for primary CNS lymphoma" (2005).
Complete Response (CR) Rate to induction therapy
Rate of CR to induction therapy is defined as the number of participants out of the total who demonstrate CR between the start of induction therapy until the end of induction therapy based on the criteria set forth in "Report of an international workshop to standardize baseline evaluation and response criteria for primary CNS lymphoma" (2005). CR includes confirmed and unconfirmed CR (CRu). CRu is defined as any participant who fulfills all criteria for CR but continues to require corticosteroid therapy or have a small but persistent enhancing abnormality on MRI related to biopsy or focal hemorrhage
Complete Response (CR) Rate after transplant, WBRT + zanubrutinib maintenance, or zanubrutinib maintenance alone
Rate of CR to is defined as the number of participants out of the total who demonstrate CR between the transplant and end of study, WBRT and end of study, or start of maintenance therapy and end of study. Response is based on the criteria set forth in "Report of an international workshop to standardize baseline evaluation and response criteria for primary CNS lymphoma" (2005). CR includes confirmed and unconfirmed CR (CRu). CRu is defined as any participant who fulfills all criteria for CR but continues to require corticosteroid therapy or have a small but persistent enhancing abnormality on MRI related to biopsy or focal hemorrhage.
Duration of Response (DOR)
DOR is defined as the duration of time from when complete or partial response is first identified to the time when progression is identified. Response is based on the criteria set forth in "Report of an international workshop to standardize baseline evaluation and response criteria for primary CNS lymphoma" (2005).
Click on the lead sponsor to view all of their trials.
Baptist Health South Florida
Lead sponsor
BeiGene
Collaborator
