Orelabrutinib with lisaftoclax and rituximab for untreated high-risk mantle cell lymphoma
A Prospective, Multicenter, Open-Label Clinical Study of Orelabrutinib Plus Lisaftoclax and Rituximab in Treatment-Naive, High-Risk Mantle Cell Lymphoma (MCL)
This trial will try combining orelabrutinib, lisaftoclax, and rituximab in people with untreated, high-risk mantle cell lymphoma to see if it increases complete remissions and delays progression.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 25 (estimated) |
| Ages | 14 Years and up |
| Sex | All |
| Sponsor | Ruijin Hospital Academic / other |
| Drugs / interventions | rituximab, orelabrutinib, obinutuzumab, ibrutinib |
| Locations | 1 site (Shanghai, Shanghai Municipality) |
| Trial ID | NCT07272499 on ClinicalTrials.gov |
What this trial studies
This is a multicenter, open-label Phase 2 trial testing the combination of a BTK inhibitor (orelabrutinib), a BCL-2 inhibitor (lisaftoclax), and the anti‑CD20 antibody rituximab in patients with untreated mantle cell lymphoma who have high‑risk features. The primary endpoint is the optimal complete response rate during the induction phase, with secondary endpoints including progression‑free survival, overall survival, objective response rate, and safety. Patients must have measurable disease and at least one high‑risk feature such as high MIPI, Ki‑67 >30%, TP53 mutation/loss, or blastoid morphology. Exploratory analyses will correlate tumor biomarkers with treatment response to identify which patients benefit most.
Who should consider this trial
Good fit: Ideal candidates are people over 14 with untreated, measurable mantle cell lymphoma (Ann Arbor stage II–IV) who have high‑risk features like MIPI 6–11, Ki‑67 >30%, TP53 mutation/loss or blastoid/pleomorphic histology and who meet routine lab and organ function requirements.
Not a fit: Patients without high‑risk disease, those who have received prior systemic therapy for MCL, or those with significant organ dysfunction or inadequate blood counts are unlikely to benefit from this protocol.
Why it matters
Potential benefit: If successful, the regimen could raise complete remission rates and prolong progression‑free survival for untreated high‑risk MCL patients.
How similar studies have performed: Previous combinations of BTK inhibitors plus BCL‑2 inhibitors and anti‑CD20 antibodies (for example SYMPATICO and BoVen regimens) have shown promising complete response rates and longer PFS in relapsed/refractory and some treatment‑naïve high‑risk MCL cohorts, supporting this approach.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * Diagnosed with MCL (mantle cell lymphoma) through flow cytometry or histopathology, and has not received prior treatment. * Age \> 14 years of age, both genders are eligible. * Ann Arbor stage II-IV; for stage II subjects, those who require systemic therapy based on the investigator's judgment are eligible. * At least one measurable lesion. * Any one of the following high-risk factors is present: MIPI score of 6-11, Ki67 \> 30%, TP53 mutation/loss or p53 protein expression \>50%, blastic or pleomorphic variation. * Laboratory tests (blood routine, liver and kidney function) meet the following requirements: a) Blood routine: White blood cell count ≥3.0×10\^9/L, absolute neutrophil count ≥1.5×10\^9/L, hemoglobin ≥90g/L, platelet count ≥75×10\^9/L. b) Liver function: Transaminases ≤2.5 times the upper limit of normal, bilirubin ≤1.5 times the upper limit of normal. c) Serum creatinine 44-133 mmol/L. * The investigator judges that the subject's life expectancy is greater than 12 weeks from the time of screening. * Willing and able to participate in all required assessments and procedures of the study protocol. Exclusion Criteria: * Patients who have previously received treatment with BTK inhibitors. * Patients with severe complications or serious infections. * Patients with uncontrolled cardiovascular diseases, coagulation disorders, connective tissue diseases, serious infectious diseases, etc. * Patients with active infections requiring systemic treatment, including bacterial, fungal, and viral infections. * HIV-infected individuals. * Patients with mental disorders or those who are known or suspected to be unable to fully comply with the study protocol. * Patients whom the investigator judges to have other conditions that make them unsuitable for participation in this study.
Where this trial is running
Shanghai, Shanghai Municipality
- Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine — Shanghai, Shanghai Municipality, China (Recruiting)
Study contacts
- Study coordinator: Li Wang
- Email: wl11194@rjh.com.cn
- Phone: +862164370045
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.