Orelabrutinib Plus Lisaftoclax and Rituximab in Untreated Mantle Cell Lymphoma With High-Risk Disease

NCT07272499 | Recruiting Phase 2 DMC

• 1 other identifier: Order2-HR
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

This multicenter, open-label, trial aims to evaluate the efficacy and safety of orelabrutinib plus lisaftoclax and rituximab in patients with high-risk mantle cell lymphoma (MCL). The primary objective is to assess the optimal complete response (CR) rate during the induction phase, with secondary objectives including progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and safety. Exploratory analysis will investigate the correlation between tumor biomarkers and treatment efficacy.

Conditions

Mantle Cell Lymphoma (MCL)

Keywords

Order2

Outcome Measures

Primary Outcomes (1)

• Complete response rate

  Percentage of participants with complete response was determined on the basis of investigator assessments according to 2014 Lugano criteria.

  End of induction treatment visit (6-8 weeks after last dose on Day 1 of Cycle 6 [Cycle length=28 days]

Secondary Outcomes (3)

• Overall Response Rate

  End of induction treatment visit (6-8 weeks after last dose on Day 1 of Cycle 6 [Cycle length=28 days]

• Progression-free survival

  Baseline up to data cut-off (up to approximately 3 years)

• Overall survival

  Baseline up to data cut-off (up to approximately 3 years)

Study Arms (1)

Orelabrutinib + Lisaftoclax + Rituximab and Orelabrutinib + Lisaftoclax Maintenance

EXPERIMENTAL

1. In induction phase, patients will receive rituximab 375 mg/m² IV on day 1/cycle; orelabrutinib 150 mg/day PO once daily; and lisaftoclax PO Cycle1(100mg day1, 200mg day2, 400mg day3, 600mg/day day4-28), Cycle2-6 600mg/day, every 28 day per cycle for 6 cycles. 2. In maintenance phase, Patients with an objective response (complete or partial) after induction therapy will recieve orelabrutinib 150 mg/day PO once daily and lisaftoclax 600mg/day PO once daily, every 28 day per cycle for 24 cycles.

Drug: Orelabrutinib; Drug: Rituximab (R); Drug: Lisaftoclax (APG-2575)

Interventions

Orelabrutinib DRUG

150mg/day PO once daily

Also known as: Induction phase

Orelabrutinib + Lisaftoclax + Rituximab and Orelabrutinib + Lisaftoclax Maintenance

Rituximab (R) DRUG

375 mg/m² IV on day 1/cycle

Also known as: Induction phase

Orelabrutinib + Lisaftoclax + Rituximab and Orelabrutinib + Lisaftoclax Maintenance

Lisaftoclax (APG-2575) DRUG

Cycle1(100mg day1, 200mg day2, 400mg day3, 600mg/day day4-28), Cycle2-6 600mg/day, PO once daily.

Also known as: Induction phase

Orelabrutinib + Lisaftoclax + Rituximab and Orelabrutinib + Lisaftoclax Maintenance

Eligibility Criteria

• Age: 14 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ruijin Hospital: lead
• First Affiliated Hospital of Wenzhou Medical University: collaborator
• The First Affiliated Hospital of Anhui Medical University: collaborator
• The Third Xiangya Hospital of Central South University: collaborator
• Qilu Hospital of Shandong University: collaborator
• Shanghai Minhang Central Hospital: collaborator
• Yangpu District Central Hospital Affiliated to Tongji University: collaborator
• Xuhui Central Hospital, Shanghai: collaborator
• Jiujiang No.1 People's Hospital: collaborator
• Shanghai 411 hospital: collaborator
• Fujian Medical University Union Hospital: collaborator

Study Sites (1)

Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, 200025, China

RECRUITING

MeSH Terms

Conditions

Lymphoma, Mantle-Cell

Interventions

orelabrutinib; Rituximab; Lisaftoclax

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Li Wang

CONTACT

+862164370045; wl11194@rjh.com.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 26, 2025
• First Posted: December 9, 2025
• Study Start: September 10, 2025
• Primary Completion (Estimated): September 10, 2028
• Study Completion (Estimated): September 10, 2028
• Last Updated: July 28, 2026

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)