Orelabrutinib with lisaftoclax and rituximab for untreated high-risk mantle cell lymphoma

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

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.

Why it matters

Who can join: the full rules

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 it's running

• 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

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

• Orelabrutinib with rituximab and optional autologous stem cell transplant for mantle cell lymphoma

  This phase 2 trial tests whether adding the oral BTK inhibitor orelabrutinib to rituximab, with optional autologous stem cell transplant and orelabrutinib maintenance, works and is safe for people with newly diagnosed non-high-risk mantle cell lymphoma.

  Recruiting Phase 2 Ruijin Hospital · Shanghai · NCT07199296

• Combining Orelabrutinib with Bendamustine and Rituximab for treating Mantle Cell Lymphoma

  This study is testing if adding Orelabrutinib to the standard treatment of Bendamustine and Rituximab can help people with intermediate- to high-risk mantle cell lymphoma who can't have a transplant feel better and live longer.

  Recruiting Phase 3 Ruijin Hospital · Shanghai · NCT06496308

• Orelabrutinib plus Pola-R-CHP as first-line treatment for intermediate- to high-risk DLBCL

  This trial tests whether adding orelabrutinib to the Pola-R-CHP regimen can improve outcomes for adults with intermediate- to high-risk newly diagnosed DLBCL.

  Recruiting at 2 sites The First Affiliated Hospital of Xiamen University · Xiamen, Fujian and 1 other locations · NCT07778212

• Orelabrutinib with Obinutuzumab and Short-Course Venetoclax in Treatment-Naïve Mantle Cell Lymphoma

  This trial tests whether a combo of orelabrutinib, obinutuzumab, and a short course of venetoclax is safe and effective for adults with newly diagnosed mantle cell lymphoma.

  Recruiting at 2 sites Phase 2 The First Affiliated Hospital with Nanjing Medical University · Changzhou, Jiangsu and 1 other locations · NCT07719556

• Orelabrutinib plus rituximab with optional lenalidomide for untreated marginal zone lymphoma using a response-adapted plan

  This will test whether giving orelabrutinib with rituximab, and adding lenalidomide for those who don't fully respond, helps people with newly diagnosed marginal zone lymphoma achieve complete remissions.

  Recruiting Phase 2 The First Affiliated Hospital with Nanjing Medical University · Nanjing, Jiangsu · NCT07448324

• PD‑1 blocker with rituximab, high‑dose methotrexate, and orelabrutinib for newly diagnosed primary or secondary CNS lymphoma

  This trial will test whether combining a PD‑1 blocker with rituximab, high‑dose methotrexate, and orelabrutinib helps people with newly diagnosed primary or secondary central nervous system diffuse large B‑cell lymphoma.

  Recruiting Phase 2 The First Affiliated Hospital with Nanjing Medical University · Nanjing, Jiangsu · NCT07410520

How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.