This phase I/Ib trial tests the safety, side effects and best dose schedule of zanubrutinib in combination with polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin (adriamycin), prednisone (pola-R-CHP) and high-dose methotrexate (HD MTX) and how well they work in treating patients with large B-cell lymphoma that is present in the central nervous system (CNS). The CNS includes the brain and spinal cord, the protective covering of the brain and spinal cord, nerves of the head, eyes, spinal cord or a combination of these organs and tissues. Zanubrutinib is a medicine that blocks a protein called Bruton tyrosine kinase (BTK). BTK helps B cells live and grow. B cells are specialized defense cells that fight infection, produce antibodies (proteins that mark damaged or diseased cells and infectious agents, like viruses, for destruction by the body’s defense systems), and support other defense cells in the body. By blocking BTK, zanubrutinib may stop or slow down the growth and activity of B cells, which can lead to improvement in the symptoms associated with B cell cancers. Polatuzumab vedotin is a monoclonal antibody, called polatuzumab, linked to a toxic agent, called vedotin. Polatuzumab is a form of targeted therapy because it attaches to specific molecules (receptors) on the surface of cancer cells, known as CD79B receptors, and delivers vedotin to kill them. Rituximab is a monoclonal antibody. It binds to a protein called CD20, which is found on B cells (a type of white blood cell) and some types of cancer cells. This may help the immune system kill cancer cells. Chemotherapy drugs, such as cyclophosphamide, doxorubicin and methotrexate work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Prednisone is in a class of medications called corticosteroids. It is used to reduce inflammation and lower the body's immune response to help lessen the side effects of chemotherapy drugs. Giving zanubrutinib in combination with pola-R-CHP and HD MTX may be safe, tolerable and/or effective in reducing or eliminating the lymphoma cells in the CNS and other areas of the body in patients with large B-cell lymphoma.
Additional locations may be listed on ClinicalTrials.gov for NCT06730542.
Locations matching your search criteria
United States
Florida
Aventura
UM Sylvester Comprehensive Cancer Center at AventuraStatus: Active
Contact: Juan Pablo Alderuccio
Phone: 347-931-2272
Coral Gables
UM Sylvester Comprehensive Cancer Center at Coral GablesStatus: Active
Contact: Juan Pablo Alderuccio
Phone: 347-931-2272
Coral Springs
UM Sylvester Comprehensive Cancer Center at Coral SpringsStatus: Active
Contact: Juan Pablo Alderuccio
Phone: 347-931-2272
Deerfield Beach
UM Sylvester Comprehensive Cancer Center at Deerfield BeachStatus: Active
Contact: Juan Pablo Alderuccio
Phone: 347-931-2272
Hollywood
UM Sylvester Comprehensive Cancer Center at HollywoodStatus: Active
Contact: Juan Pablo Alderuccio
Phone: 347-931-2272
Miami
UM Sylvester Comprehensive Cancer Center at KendallStatus: Active
Contact: Juan Pablo Alderuccio
Phone: 347-931-2272
University of Miami Miller School of Medicine-Sylvester Cancer CenterStatus: Active
Contact: Juan Pablo Alderuccio
Phone: 347-931-2272
Plantation
UM Sylvester Comprehensive Cancer Center at PlantationStatus: Active
Contact: Juan Pablo Alderuccio
Phone: 347-931-2272
PRIMARY OBJECTIVE:
I. Determine the recommended Phase 2 dose schedule of pola-R-CHP in combination with HD MTX and zanubrutinib (high-dose methotrexate, zanubrutinib, polatuzumab vedotin, rituximab, cyclophosphamide, adriamycin, and prednisone [MRZ-pola-CHP]) in patients with secondary central nervous system involvement by large B-cell lymphoma (SCNSL).
SECONDARY OBJECTIVES:
I. To evaluate the overall response rate (ORR) after 5 cycles of MRZ-pola-CHP (6 cycles of pola-R-CHP with HD MTX).
II. To evaluate the effect of MRZ-pola-CHP on progression-free survival (PFS) in patients with SCNSL.
III. To evaluate the effect of MRZ-pola-CHP on overall survival (OS) in patients with SCNSL.
IV. To evaluate the safety and tolerability of MRZ-pola-CHP in patients with SCNSL.
EXPLORATORY OBJECTIVES:
I. To analyze blood and cerebrospinal fluid (CSF) for circulating tumor deoxyribonucleic acid (ctDNA) for minimal residual disease (MRD), whole exome sequencing (WES), and early identification of emerging clones.
II. To analyze the concentration of zanubrutinib in blood and CSF samples.
III. To analyze tissue samples for genomic markers of disease.
IV. To evaluate cognitive function and the association of treatment with change in cognitive functions at baseline and after 5 cycles of MRZ-pola-CHP (6 cycles of pola-R-CHP with HD MTX).
OUTLINE: This is a dose-schedule escalation study of zanubrutinib in combination with standard of care pola-R-CHP and HD MTX followed by a dose-schedule expansion study.
INDUCTION: Patients receive HD MTX intravenously (IV), intramuscularly (IM) or subcutaneously (SC), polatuzumab vedotin IV, rituximab IV, cyclophosphamide IV or orally (PO), doxorubicin IV and prednisone PO once each cycle per standard of care. Starting with cycle 2, patients receive zanubrutinib PO twice daily (BID) or once daily (QD) on days 4-21, on days 8-21 or on days 15-21 of each cycle. Cycles repeat every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.
AUTOLOGOUS STEM-CELL TRANSPLANT (ASCT): After 6 cycles, patients achieving systemic or CNS partial response (PR) undergo consolidation ASCT per standard of care.
MAINTENANCE: Patients receive zanubrutinib PO on days 1-28 of each cycle. Cycles repeat every 28 days for up to 24 months in the absence of disease progression or unacceptable toxicity.
Additionally, patients undergo blood and CSF sample collection throughout the study.
After completion of study treatment, patients are followed up at 30 days, then every 90 days up to 1 year, followed by every 6 months for up to 3 years.
Lead OrganizationUniversity of Miami Miller School of Medicine-Sylvester Cancer Center
Principal InvestigatorJuan Pablo Alderuccio