A Randomized Phase 2 Study of Bendamustine, Rituximab, Cytarabine (AraC) Induction With Zanubrutinib (BRAZAN) Followed by Zanubrutinib/Rituximab +/- Sonrotoclax Maintenance in Treatment-Naïve Mantle Cell Lymphoma
Summary
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)
Detailed description
This Phase 2, multi-center, randomized study is 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 MCL. These specific maintenance therapy combinations are investigational and are being evaluated to see if the therapies may lengthen the time before MCL returns after initial therapy. After completing induction therapy, participants will be randomized into one of two groups: Arm A: zanubrutinib + rituximab or Arm B: zanubrutinib + rituximab + sonrotoclax. Randomization means a participant is placed into a study group by chance. The U.S. Food and Drug Administration (FDA) has approved bendamustine, cytarabine, rituximab, and zanubrutinib for the treatment of other lymphomas and/or blood cancers. The FDA has approved rituximab as a treatment option for Mantle Cell Lymphoma (MCL). The FDA has also approved zanubrutinib for mantle cell lymphoma, but only after trying other therapies first. The FDA has not approved sonrotoclax as a treatment for Mantle Cell Lymphoma (MCL). However sonrotoclax works similarly to a drug called venetoclax, which is also sometimes used to treat mantle cell lymphoma. The U.S. Food and Drug Administration (FDA) has approved venetoclax for the treatment of other blood cancers. The research study procedures include screening for eligibility, in-clinic treatment visits, electrocardiograms (ECGs), Positron Emission Tomography (PET) scans, Computerized Tomography CT) scans, blood tests, urine tests, lymph node biopsies, and bone marrow biopsies. It is expected that about 60 people will take part in this research study. The induction therapy will be 6 "cycles", or rounds of treatment, which will last for up to a little over 5 months. The maintenance therapy will last for up to 2 years. * Induction phase: * Bendamustine/Rituximab + Zanubrutinib for 3 cycles * Rituximab/Cytarabine for 3 cycles * Maintenance phase - either: * A) Zanubrutinib + Rituximab, or * B) Zanubrutinib + Sonrotoclax + Rituximab BeiGene, Ltd., a pharmaceutical company, is also supporting this research study by providing the drugs zanubrutinib and sonrotoclax and other funding support.
Arms & interventions
- DrugBendamustine
An Alkylating agent, multi-dose vial, via intravenous (into the vein) infusion per institutional standard of care.
- DrugRituximab
An Anti-CD20 antibody, single-use vials, via intravenous infusion per institutional standard of care.
- DrugCytarabine
An Antineoplastic, single dose vial via intravenous infusion per institutional standard of care.
- DrugZanubrutinib
A BTK inhibitor, capsule taken orally per protocol.
- DrugSonrotoclax
A BCL 2 Protein Inhibitor, immediate release tablet, taken orally per protocol.
Outcome measures
Primary
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.
Time frame: Up to 125 weeks
Secondary
Grade 4 Treatment-Related Toxicity Rate of zanubrutinib in combination with sonrotoclax and rituximab
Time frame: Up to 125 weeks
Grade 4 Treatment-Related Toxicity Rate of zanubrutinib in combination with BR
Time frame: Up to 125 weeks
Complete Response Rate (CRR) after Maintenance Treatment in doublet arm
Time frame: Up to 125 weeks
Complete Response Rate (CRR) after Maintenance Treatment in triplet arm
Time frame: Up to 125 weeks
Best Overall Response (BRR)
Time frame: Up to 125 weeks
Best Complete response (CR) rate
Time frame: Up to 125 weeks
Overall response rate (ORR) after 3 cycles of zanubrutinib + BR
Time frame: Up to 125 weeks
Complete response rate (CRR) after 3 cycles of zanubrutinib + BR
Time frame: Up to 125 weeks
Partial response rate (PRR) after 3 cycles of zanubrutinib + BR
Time frame: Up to 125 weeks
Overall response rate (ORR) after 6 cycles of BRAZAN induction
Time frame: Up to 125 weeks
Complete response rate (CRR) after 6 cycles of BRAZAN induction
Time frame: Up to 125 weeks
Partial response rate (PRR) after 6 cycles of BRAZAN induction
Time frame: Up to 125 weeks
Overall response rate (ORR) after the entire treatment course
Time frame: Up to 125 weeks
Complete response rate (CRR) after the entire treatment course
Time frame: Up to 125 weeks
Partial response rate (PRR) after the entire treatment course
Time frame: Up to 125 weeks
Overall response rate (ORR) after the entire treatment course in doublet arm
Time frame: Up to 125 weeks
Complete response rate (CRR) after the entire treatment course in doublet arm
Time frame: Up to 125 weeks
Partial response rate (PRR) after the entire treatment course in doublet arm
Time frame: Up to 125 weeks
Overall response rate (ORR) after the entire treatment course in triplet arm
Time frame: Up to 125 weeks
Complete response rate (CRR) after the entire treatment course in triplet arm
Time frame: Up to 125 weeks
Partial response rate (PRR) after the entire treatment course in triplet arm
Time frame: Up to 125 weeks
Duration of response (DOR)
Time frame: Up to 10 years
Duration of complete response (DOCR)
Time frame: Up to 10 years
Duration of response (DOR) in doublet arm
Time frame: Up to 10 years
Duration of complete response (DOCR) in doublet arm
Time frame: Up to 10 years
Duration of response (DOR) in triplet arm
Time frame: Up to 10 years
Median Duration of complete response (DOCR) in triplet arm
Time frame: Up to 10 years
Progression free survival (PFS)
Time frame: Up to 10 years
Progression free survival (PFS) in doublet arm
Time frame: Up to 10 years
Progression free survival (PFS) in triplet arm
Time frame: Up to 10 years
Overall Survival (OS)
Time frame: Up to 10 years
Overall Survival (OS) in doublet arm
Time frame: Up to 10 years
Overall Survival (OS) in triplet arm
Time frame: Up to 10 years
Rate of peripheral blood (PB) MRD-negativity after 6 cycles of induction therapy
Time frame: Up to 125 weeks
Rate of peripheral blood (PB) MRD-negativity after 12 cycles of maintenance treatment in doublet arm
Time frame: Up to 125 weeks
Rate of peripheral blood (PB) MRD-negativity after 12 cycles of maintenance treatment in triplet arm
Time frame: Up to 125 weeks
Rate of peripheral blood (PB) MRD-negativity after 24 cycles of maintenance treatment in doublet arm
Time frame: Up to 125 weeks
Rate of peripheral blood (PB) MRD-negativity after 24 cycles of maintenance treatment in triplet arm
Time frame: Up to 125 weeks
Best rate of peripheral blood (PB) MRD-negativity after up to 24 cycles of maintenance treatment in doublet arm
Time frame: Up to 125 weeks
Best rate of peripheral blood (PB) MRD-negativity after up to 24 cycles of maintenance treatment in triplet arm
Time frame: Up to 125 weeks
Eligibility criteria
Study locations (7)
Mayo Clinic Arizona
Phoenix, Arizona, 85054
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
Brigham and Women's Hospital
Boston, Massachusetts, 02215
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Mayo Clinic
Rochester, Minnesota, 55905
Washington University
St Louis, Missouri, 63110
Memorial Sloan Kettering Cancer Center
New York, New York, 10065