Combination treatment for untreated Mantle Cell Lymphoma patients

An Open-label, Multi-center, Single-arm Study to Evaluate the Efficacy and Safety of Sonrotoclax, Zanubrutinib and CD20mab in Untreated MCL Patients

This study is testing a new combination treatment without chemotherapy for people with untreated Mantle Cell Lymphoma to see if it can improve their health and survival.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Tianjin Medical University Cancer Institute and Hospital (Academic / other)
• Drugs / interventions: ibrutinib, zanubrutinib, chimeric antigen receptor, chemotherapy, immunotherapy
• Locations: 1 site (Tianjin)
• Trial ID: NCT06463691 on ClinicalTrials.gov

What this trial studies

This open-label, multi-center, single-arm study evaluates the efficacy and safety of a combination regimen of sonrotoclax, zanubrutinib, and CD20mab in patients with untreated Mantle Cell Lymphoma (MCL). The study aims to provide a chemotherapy-free treatment option for patients who may not tolerate traditional chemotherapy due to its toxicity. By focusing on a novel immunotherapy approach, the study seeks to improve patient outcomes and survival rates in this population. Participants will be monitored for both efficacy and safety throughout the trial.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18 and older with a confirmed diagnosis of untreated Mantle Cell Lymphoma.

Not a fit: Patients with prior treatment for MCL or those with significant comorbidities affecting their performance status may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could offer a safer, effective alternative to chemotherapy for patients with untreated MCL.

How similar studies have performed: While the combination of these specific agents is novel, similar immunotherapy approaches have shown promise in treating other hematological malignancies.

Eligibility criteria

Inclusion Criteria:

1. Subject must be ≥ 18 years of age.
2. Subject must have a confirmed Mantle Cell Lymphoma (MCL) diagnosis according to WHO (2008) criteria.
3. Previously untreated MCL
4. Subject has an Eastern Cooperative Oncology Group (ECOG) performance score of ≤ 2.
5. Nonsterile men and women of child-bearing potential must agree to use highly effective contraceptives (e.g., 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.
6. Subject must have adequate bone marrow function at Screening as follows:

   a.Absolute Neutrophil Count (ANC) ≥ 1.0 x 109/L (neutropenia due to marrow infiltration may be supported by growth factors);

   • b. Platelets ≥ 75,000/mm3 (or ≥ 50,000/mm3 for patients with bone marrow involvement of lymphoma) within 7 days
7. Subject must have adequate coagulation, renal, and hepatic function, per laboratory reference range at Screening as follows:

   1. aPTT and PT not to exceed 1.5 × the upper limit of normal (ULN); Serum creatinine not to exceed 2 x ULN, and a calculated creatinine clearance of at least 50 mL/min using the Cockcroft-Gault equation or a 24-hour urine collection;
   2. AST or ALT ≤ 3.0 × the upper normal limit (ULN) of institution's normal range; Bilirubin ≤ 1.5 × ULN. Subjects with documented Gilbert's Syndrome may have a bilirubin \> 1.5 × ULN.
8. Written informed consent form according to GCP and national regulations.

Exclusion Criteria:

1. Subject has known central nervous system involvement by MCL.
2. Prior malignancy other than MCL within the past 3 years, except for curatively treated basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix or breast, or localized Gleason score 6 prostate cancer.
3. Receiving any treatment with a moderate CYP3A4 inhibitor or strong CYP3A4 inhibitor or inducer within 2 weeks (or 5 half-lives, whichever is longer) before the first dose of study drug or requiring long-term use of strong CYP3A4 inhibitors or inducers.
4. Prior ASCT within the last 3 months; or prior autologous chimeric antigen receptor-T cell therapy within the last 3 months; or prior allogeneic stem cell transplant within the last 6 months or currently has an active graft-vs-host disease requiring the use of immunosuppressants.
5. Major surgery within 4 weeks of screening.
6. Clinically significant cardiovascular disease including the following:

   1. Myocardial infarction within 6 months before screening
   2. Unstable angina within 3 months before screening
   3. New York Heart Association class III or IV congestive heart failure
   4. History of clinically significant arrhythmias (eg, sustained ventricular tachycardia, ventricular fibrillation)
   5. QT interval corrected based on Fridericia's formula (QTcF) \> 480 msec.
   6. History of Mobitz II second-degree or third-degree heart block without a permanent pacemaker in place
   7. Uncontrolled hypertension as indicated by a minimum of 2 consecutive blood pressure measurements showing systolic blood pressure \> 170 mmHg and diastolic blood pressure \> 105 mmHg at screening.
7. Prior exposure to a BCL2 inhibitor (e.g., venetoclax/ABT-199).
8. Prior exposure to a BTK inhibitor (e.g., ibrutinib, zanubrutinib).
9. History of hypersensitivity to excipient(s) of the sonrotoclax tablet.
10. Patients with unresolved hepatitis B or C infection or known HIV-positive infection：

    1. Presence of hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb). Patients with presence of HBcAb, but absence of HBsAg, are eligible if hepatitis B virus (HBV) DNA is undetectable (\< 20 IU/mL), and if they are willing to undergo monitoring for HBV reactivation.
    2. Presence of hepatitis C virus (HCV) antibody. Patients with presence of HCV antibody are eligible if HCV RNA is undetectable (\< 15 IU/mL), and if they are willing to undergo monitoring for HCV reactivation.
11. 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.
12. Pregnant or lactating women.
13. History of stroke or intracranial hemorrhage within 6 months before the first dose of study drug.
14. Underlying medical conditions that, in the investigator's opinion, will render the administration of study drug hazardous or obscure the interpretation of safety or efficacy results.

Where this trial is running

Tianjin

• Tianjin Medical University Cancer Institute and Hospital — Tianjin, China (Recruiting)

Study contacts

• Study coordinator: Huilai Zhang, MD, PhD

Conditions MCL; Sonrotoclax; Zanubrutinib