Bendamustine and Rituximab With or Without Orelabrutinib in MCL Treatment

Shanghai Jiao Tong University

Status and phase: Enrolling; Phase 3

Conditions: Mantle Cell Lymphoma (MCL)

Treatments: Drug: Venetoclax; Drug: Rituximab; Drug: Orelabrutinib; Drug: Bendamustine

Study type: Interventional

Funder types: Other

Identifiers

NCT06496308

ORDER

Details and patient eligibility

About

This multicenter, open-label, randomized controlled trial aims to evaluate the efficacy and safety of Orelabrutinib in combination with Bendamustine and Rituximab (OBR) versus Bendamustine and Rituximab (BR) in patients with intermediate- to high-risk mantle cell lymphoma (MCL) who are ineligible for transplantation. The primary objective is to assess the 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.

Enrollment: 78 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Diagnosed with MCL (mantle cell lymphoma) through flow cytometry or histopathology, and has not received prior treatment.
• Age > 18 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.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2.
• Any one of the following high-risk factors is present: MIPI score of 4-11, Ki67 > 50%, TP53 abnormality, blastic or pleomorphic variation.
• Patients who are not suitable candidates for autologous hematopoietic stem cell transplantation.
• 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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78 participants in 4 patient groups, including a placebo group

Orelabrutinib + Bendamustine + Rituximab (OBR)

Experimental group

Description:

In induction phase, patients will be randomized in two groups, one is OBR and another is BR. Patients in OBR group will receive rituximab 375 mg/m² IV on day 1, bendamustine 90 mg/m² IV on day 1 and 2, and orelabrutinib 150mg/day PO once daily, every 28 day per cycle for 6 cycles.

Treatment:

Drug: Bendamustine

Drug: Orelabrutinib

Drug: Rituximab

Bendamustine + Rituximab (BR)

Placebo Comparator group

Description:

In induction phase, patients will be randomized in two groups, one is OBR and another is BR. Patients in BR group will receive rituximab 375 mg/m² IV on day 1, bendamustine 90 mg/m² IV on day 1 and 2, every 28 day per cycle for 6 cycles.

Treatment:

Drug: Bendamustine

Drug: Rituximab

Orelabrutinib + Venetoclax (OV)

Other group

Description:

In maintanance phase, patients will receive different medical regimen according to their TP53 mutation and blastic and pleomorphic variants status. Patients with TP53 mutation or blastic and/or pleomorphic variant will receive orelabrutinib 150mg/day PO once daily and venetoclax for up to 2 years, the dosing of Venetoclax is escalated gradually to reach a target dose of 400 mg.

Treatment:

Drug: Orelabrutinib

Drug: Venetoclax

Orelabrutinib (O)

Other group

Description:

In maintanance phase, patients will receive different medical regimen according to their TP53 mutation and blastic and pleomorphic variants status. Patients without TP53 mutation or blastic and/or pleomorphic variant will receive orelabrutinib 150mg/day PO once daily for up to 2 years.

Treatment:

Drug: Orelabrutinib