Zanubrutinib treatment for young patients with untreated Mantle Cell Lymphoma

A Perspective Study of Zanubrutinib-based Induction and Maintenance Therapy in Young and Fit Patients With Untreated Mantle Cell Lymphoma (BRIDGE)

This study is testing if a new treatment combining Zanubrutinib with standard therapy can help young patients with untreated Mantle Cell Lymphoma before they undergo stem cell transplantation.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 47 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: Sun Yat-sen University (Academic / other)
• Drugs / interventions: zanubrutinib
• Locations: 1 site (Guangzhou, Guangdong)
• Trial ID: NCT04736914 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the use of Zanubrutinib as an induction therapy followed by autologous stem cell transplantation (ASCT) and maintenance therapy in young and fit patients diagnosed with untreated Mantle Cell Lymphoma (MCL). The study will begin with a safety run-in phase involving 6 patients to monitor for any toxicities during the initial treatment cycle. If the safety profile is acceptable, the trial will expand to include approximately 47 patients aged 18-65 years, who will receive a combination of R-CHOP and Zanubrutinib for induction, followed by maintenance therapy with Zanubrutinib. The goal is to assess both the efficacy and safety of this treatment regimen.

Who should consider this trial

Good fit: Ideal candidates for this study are young adults aged 18-65 with previously untreated, histologically confirmed Mantle Cell Lymphoma.

Not a fit: Patients with advanced MCL who are not fit for high-dose treatment or those with significant comorbidities may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new effective option for young patients with untreated Mantle Cell Lymphoma.

How similar studies have performed: While there is limited published data on the specific combination of BTK inhibitors like Zanubrutinib with standard therapies, similar approaches have shown promise in other studies.

Eligibility criteria

Inclusion Criteria:

1. 1. Histologically confirmed diagnosis of MCL according to WHO classification
2. Previously untreated MCL
3. Suitable for high-dose treatment including high-dose Ara-C
4. Age ≥ 18 years and ≤ 65 years
5. Stage II-IV (Ann Arbor)
6. Measurable disease by computed tomography (CT)/magnetic resonance imaging (MRI). Measurable disease was defined as at least 1 lymph node \> 1.5 cm in longest diameter and measurable in 2 perpendicular dimensions; in case of bone marrow infiltration only, bone marrow aspiration and biopsy are mandatory for all staging evaluations
7. ECOG performance status ≤ 2
8. The following laboratory values at screening (unless related to MCL):

   * Absolute neutrophil count (ANC) ≥ 1×10⁹/L
   * Platelets ≥ 75×10⁹/L (platelets ≥ 50×10⁹/L with bone marrow involvement)
   * Transaminases (AST and ALT) ≤ 3 × upper limit of normal (ULN)
   * Total bilirubin ≤ 2 × ULN (unless documented Gilbert's syndrome)
   * Calculated creatinine clearance ≥ 30 mL/min
9. International normalized ratio ≤ 1.5 and activated partial thromboplastin time ≤ 1.5 x upper limit of normal. If a factor inhibitor was present with prolongation of the international normalized ratio or activated partial thromboplastin time.
10. Sexually active men and women of child-bearing potential must agree to use highly effective contraceptives (eg, condoms, implants, injectables, combined oral contraceptives, intrauterine devices, sexual abstinence, or sterilized partner) while on study; this should be maintained for 90 days after the last dose of study drug
11. Life expectancy of\> 3 months
12. Written informed consent form according to GCP and national regulations

Exclusion Criteria:

1. Known CNS involvement of MCL
2. Major surgery within 4 weeks of screening
3. Prior hematopoietic stem cell transplantation
4. Concomitant or previous malignancies within the last 2 years other than basal cell skin cancer or in situ uterine cervix cancer
5. Clinically significant cardiovascular disease such as uncontrolled arrhythmias and hypertension , congestive heart failure, or myocardial infarction within 6 months of Screening, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification or LVEF below 50%（AHA，2016）
6. QTcF \> 450 msec or other significant electrocardiogram (ECG) abnormalities including second-degree atrioventricular block Type II, or third-degree atrioventricular block
7. Clinically significant hypersensitivity (eg, anaphylactic or anaphylactoid reactions to the compound of zanubrutinib itself or to the excipients in its formulation)
8. Requires treatment with strong CYP3A inhibitors or strong CYP3A inducers
9. Unable to swallow capsules or disease significantly affecting gastrointestinal function such as malabsorption syndrome, resection of the stomach or small bowel, bariatric surgery procedures, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction
10. Patients with unresolved hepatitis B or C infection or known HIV positive infection
11. Active infection including infections requiring oral or intravenous antimicrobial therapy
12. Any life-threatening illness, medical condition, or organ system dysfunction that, in the investigator's opinion, could have compromised the patient's safety, or put the study at risk
13. History of stroke or intracranial hemorrhage within 6 months before first dose of study drug
14. Pregnancy or lactation
15. Participation in another clinical trial within 30 days before enrollment in this study
16. poor compliance

Where this trial is running

Guangzhou, Guangdong

• Department of Medical Oncology, Sun Yat-sen University Cancer Center — Guangzhou, Guangdong, China (Recruiting)

Study contacts

• Study coordinator: huang huiqiang

Conditions Mantle Cell Lymphoma