Orelabrutinib and Rituximab With Optional Autologous Hematopoietic Stem Cell Transplantation in MCL Treatment

Shanghai Jiao Tong University

Status and phase: Enrolling; Phase 2

Conditions: Mantle Cell Lymphoma (MCL)

Treatments: Drug: orelabrutinib maintenance; Drug: BEAM (carmustine (BCNU), etoposide, cytarabine, melphalan); Drug: Rituximab (R); Drug: Orelabrutinib

Study type: Interventional

Funder types: Other

Identifiers

NCT07199296

OR+/-ASCT

Details and patient eligibility

About

This multicenter, open-label, trial aims to evaluate the efficacy and safety of orelabrutinib in combination with rituximab with optional autologous hematopoietic stem cell transplantation in patients with non-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.

Enrollment: 45 estimated patients

Sex: All

Ages: 14+ 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 > 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.
• 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.
• Any one of the following high-risk factors is present: MIPI score of 6-11, Ki67 > 30%, TP53 abnormality, blastic or pleomorphic variation.
• 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: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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45 participants in 1 patient group

Experimental: Orelabrutinib + Rituximab +/- ASCT and Orelabrutinib Maintenance

Experimental group

Description:

1. In induction phase, patients will receive rituximab 375 mg/m² IV on day 1,8,15,22 in Cycle 1, then day 1/cycle, and orelabrutinib 150 mg/day PO once daily, every 28 day per cycle for 6 cycles. Patients with an objective response (complete or partial) after induction therapy, who meet ASCT eligibility criteria and consent, proceed to transplantation. 2. ASCT: BEAM pretreatment. Patients receive carmustine on day -7, etoposide on days -6-(-3), cytarabine on days -6-(-3) and melphalan on day -2. 3. In maintenance phase, patients will recieve orelabrutinib 150 mg/day PO once daily until disease progression or intolerable toxicity.

Treatment:

Drug: Orelabrutinib

Drug: Rituximab (R)

Drug: BEAM (carmustine (BCNU), etoposide, cytarabine, melphalan)

Drug: orelabrutinib maintenance