This study aims to evaluate the efficacy and safety of an induction regimen combining Bendamustine, Rituximab, Cytarabine (AraC), and Zanubrutinib (BRAZAN), followed by maintenance therapy with Zanubrutinib and Rituximab with or without Sonrotoclax in participants with Mantle Cell Lymphoma (MCL).
The names of the study drugs involved in this study are:
* bendamustine (a type of alkylating agent) * rituximab (a type of monoclonal antibody) * cytarabine (a type of antineoplastic) * zanubrutinib (a type of kinase inhibitor) * sonrotoclax (a type of BCL2 inhibitor)
Histologically confirmed diagnosis of mantle cell lymphoma, with review of the diagnostic pathology specimen at one of the participating institutions. Whenever possible, the Ki67 fraction should be reported or evaluated, cytogenetics should be performed, and TP53 status should be assessed (preferably by next-generation sequencing; immunohistochemical staining would be next-preferred).
Prior radiotherapy for localized disease is permitted.
A course of radiotherapy for urgent symptomatic disease is also permitted. Short-course systemic corticosteroids is permissible for disease control (must be < 7 days and ≤ 100mg/day of prednisone or ≤ 20mg/day of dexamethasone, or equivalent). Steroids must be discontinued prior to study treatment.
Measurable disease, defined as ≥1 measurable nodal lesion (long axis >1.5 cm or short axis >1.0 cm) or ≥1 measurable extra-nodal lesion (long axis >1.0 cm) on PET, CT, or magnetic resonance imaging (MRI). Disease should be FDG-avid based on PET.
Known central nervous system involvement.
Known active infection requiring systemic antimicrobial therapy at trial enrollment.
Patients, who have had a major surgery or significant traumatic injury within 4 weeks of start of study drug, patients who have not recovered from the side effects of any major surgery (defined as requiring general anesthesia).
Participants who require warfarin or other vitamin K antagonists for anticoagulation. Other anticoagulants including direct oral anticoagulants (i.e. apixaban, rivaroxaban) and low-molecular weight heparin are allowed.
Sequential
Bendamustine
DrugAn Alkylating agent, multi-dose vial, via intravenous (into the vein) infusion per institutional standard of care.
Rituximab
DrugAn Anti-CD20 antibody, single-use vials, via intravenous infusion per institutional standard of care.
Cytarabine
DrugAn Antineoplastic, single dose vial via intravenous infusion per institutional standard of care.
Zanubrutinib
DrugA BTK inhibitor, capsule taken orally per protocol.
Sonrotoclax
DrugA BCL 2 Protein Inhibitor, immediate release tablet, taken orally per protocol.
Complete Response Rate (CRR) after 1-year of Maintenance Treatment
CRR after maintenance treatment is defined as the proportion of participants who experienced complete response (CR) with peripheral blood (PB) MRD-negativity after 1-year of maintenance therapy.
Grade 4 Treatment-Related Toxicity Rate of zanubrutinib in combination with sonrotoclax and rituximab
The percentage of participants who experienced a maximum grade 4 treatment-related adverse event based on the Common Toxicity Criteria for Adverse events Version 5.0 (CTCAEv5) as reported on case report forms.
Grade 4 Treatment-Related Toxicity Rate of zanubrutinib in combination with BR
The percentage of participants who experienced a maximum grade 4 treatment-related adverse event based on the Common Toxicity Criteria for Adverse events Version 5.0 (CTCAEv5) as reported on case report forms.
Complete Response Rate (CRR) after Maintenance Treatment in doublet arm
CRR after maintenance treatment is defined as the proportion of participants who experienced complete response (CR) with PB MRD-negativity after maintenance therapy.
Complete Response Rate (CRR) after Maintenance Treatment in triplet arm
CRR after maintenance treatment is defined as the proportion of participants who experienced complete response (CR) with PB MRD-negativity after maintenance therapy.
Click on the lead sponsor to view all of their trials.
