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New treatment option for Mantle Cell Lymphoma
Official title BRAZAN: 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
ClinicalTrials.gov ID: NCT06854003
What this study is testing
What is Bendamustine?
Bendamustine is an investigational medicine, given as an infusion into a vein, being studied as a potential treatment for mantle cell lymphoma.
Also referred to as Bendamustine hydrochloride, C16H21Cl2N3O2 · HCl.
Plain-language explanation of the investigational treatment - it is being studied and is not an approved or proven therapy. The study team can confirm the details.
- What it's testing
- 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)
- Phase 2: a mid-size study of how well it works
- Time commitment: about 2 years
- Which group you join is decided by chance.
A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.
Who can take part
Ages 18 and older
You may be able to join if
- Histologically confirmed diagnosis of mantle cell lymphoma, with review of the diagnostic pathology specimen at one of the participating...
- No prior anti-lymphoma therapy, with the following exceptions:
- 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...
- 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...
You likely can't join if
- 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...
- Participants who require warfarin or other vitamin K antagonists for anticoagulation. Other anticoagulants including direct oral anticoagulants (i.e...
- History of severe bleeding disorder such as hemophilia A, hemophilia B, von Willebrand disease, or history of spontaneous bleeding requiring blood...
- History of stroke or intracranial hemorrhage within 6 months of first dose of zanubrutinib.
See the full eligibility criteria
Who can join
- 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...
- No prior anti-lymphoma therapy, with the following exceptions:
- 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...
- 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...
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. (Appendix A)
- Age ≥18 years and considered a candidate for high-dose cytarabine by the treating physician.
- Adequate hematologic and organ function defined as:
- Absolute neutrophil count ≥ 1.0 x109/L, or ≥ 0.5 x109/L if bone marrow involvement (use of growth factor support allowed).
- Hemoglobin ≥ 8 g/dL and independent of transfusion within 7 days of screening.
- Platelets ≥ 100 x109/L, or ≥ 50 x109/L if bone marrow involvement, and independent of transfusion within 7 days of screening.
- Estimated CrCl ≥ 30mL/min (by Cockcroft-Gault formula or by 24-hour urine collection).
- AST/ALT \< 2.5 X institutional upper limit of normal (ULN), or \< 5.0 X institutional ULN if documented liver involvement of lymphoma.
- Total bilirubin \< 2.0 X ULN (unless active hemolysis); for people with Gilbert's Syndrome, direct bilirubin \< 1.5 X ULN.
- Patients with known infection with human immunodeficiency virus (HIV) are eligible, provided all 3 of the following are true: 1) presence of controlled disease, defined as CD4 count ≥ 200/uL and an undetectable viral...
- Willingness to provide a pre-treatment tumor sample by core needle or excisional surgical biopsy. A fresh biopsy is strongly encouraged, but an archival sample is acceptable if it is collected within 90 days and without...
- Willingness to remain abstinent or to use two effective contraceptive methods that result in a failure rate of \<1% per year from screening until at least:
- 6 months after the last dose of bendamustine,
- 6 months after the last dose of cytarabine,
- 90 days after the last dose of zanubrutinib,
- 90 days after the last dose of sonrotoclax, and/or
- 12 months after the last dose of rituximab, whichever of the above is longest. Examples of contraceptive methods with a failure rate of \<1% per year include:
- Tubal ligation, male sterilization, hormonal implants, established proper use of hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices.
- Alternatively, two methods (e.g., two barrier methods such as a condom and a cervical cap) may be combined to achieve a failure rate of \<1% per year. Barrier methods must always be supplemented with the use of a...
- True abstinence is acceptable when this is in line with the preferred and usual lifestyle of the subject. In contrast, periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal...
- Ability to understand and the willingness to sign a written informed consent document.
What rules you out
- 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...
- 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.
- History of severe bleeding disorder such as hemophilia A, hemophilia B, von Willebrand disease, or history of spontaneous bleeding requiring blood transfusions or other medical interventions.
- History of stroke or intracranial hemorrhage within 6 months of first dose of zanubrutinib.
- History of significant or life-threatening hemorrhage within 3 months of first dose of zanubrutinib.
- History of uncontrolled autoimmune hemolytic anemia or immune thrombocytopenia, unless these conditions are related to the underlying malignancy.
- Active hepatitis C infection. Patients with presence of HCV antibody are eligible if HCV RNA is undetectable (NOTE: the limit of detection for HCV RNA must have a sensitivity of \< 15 IU/mL). people who received...
- Active hepatitis B infection. Patients with positive hepatitis B serologies with undetectable HBV DNA (NOTE: the limit of detection for HBV DNA must have a sensitivity of \< 20 IU/mL) are permitted in the trial but...
- Prior history of another malignancy unless treated with curative intent and disease-free for at least 3 years at time of screening with expected low risk of recurrence during expected timeframe of study participation...
- Patients with the following cardiac conditions will be excluded:
- New York Heart Association Class III or IV heart failure.
- Myocardial infarction within 6 months of screening.
- Unstable angina within 3 months prior to screening.
- Active uncontrolled arrhythmia.
- History of clinically significant ventricular arrhythmias within 6 months of screening (eg sustained Vtach, Vfib, torsades de pointes).
- History of Mobitz II second-degree or third-degree heart block without a permanent pacemaker in place.
- Uncontrolled hypertension as indicated by ≥ 2 consecutive blood pressure measurements showing systolic blood pressure \> 170 mm Hg and diastolic blood pressure \> 105 mm Hg at screening.
- Screening 12-lead EKG showing a baseline QTcF (Fridericia's correction) \> 480 msec.
- Unable to swallow capsules or disease significantly affecting gastrointestinal function, such as malabsorption syndrome.
- Participants receiving any medications or substances that are strong CYP3A inducers. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical...
- Patients who are pregnant, breast-feeding, or intending to become pregnant during the study.
- Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study or limit adherence to study requirements.
- Inability to comply with protocol mandated restrictions.
The study team makes the final eligibility decision.
Where it's taking place
- Phoenix, Arizona, United States
- Boston, Massachusetts, United States
- Rochester, Minnesota, United States
- St Louis, Missouri, United States
- New York, New York, United States
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The study runs about 2 years per participant, based on its public description. The team confirms the exact schedule and number of visits before you enroll.
Who can join this trial?
This study is enrolling all sexes, 18 years and older. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Phoenix, Arizona, United States; Boston, Massachusetts, United States; Rochester, Minnesota, United States; St Louis, Missouri, United States; New York, New York, United States. Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from ClinicalTrials.gov; the study team decides eligibility.