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

NCT07199296 | Recruiting Phase 2 DMC

• 1 other identifier: OR+/-ASCT
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Mantle Cell Lymphoma (MCL)

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)

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

EXPERIMENTAL

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.

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

Interventions

Orelabrutinib DRUG

orelabrutinib 150mg/day PO once daily

Also known as: Induction phase

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

Rituximab (R) DRUG

rituximab 375 mg/m² IV on day 1, 8, 15, 22 in Cycle 1, then day 1/cycle

Also known as: Induction phase

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

BEAM (carmustine (BCNU), etoposide, cytarabine, melphalan) DRUG

the reference doses are as follows (each center may adjust them as appropriate based on actual conditions): carmustine 300mg/m² IV d-1; etoposide 200mg/m² IV d-6-(-3); cytarabine 200mg/m² IV d-6-(-3); melphalan 140mg/m² IV d-2.

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

orelabrutinib maintenance DRUG

orelabrutinib 150mg/day PO once daily

Experimental: Orelabrutinib + Rituximab +/- ASCT and Orelabrutinib 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.
• 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.
• 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.

Sponsors & Collaborators

• Ruijin Hospital: lead
• Fujian Medical University Union Hospital: collaborator
• The First Affiliated Hospital of Anhui Medical University: collaborator
• The Third Xiangya Hospital of Central South University: collaborator
• First Affiliated Hospital of Wenzhou Medical University: collaborator
• Qilu Hospital of Shandong University: collaborator
• Huadong Hospital: collaborator

Study Sites (1)

Ruijin Hospital

Shanghai, 200025, China

RECRUITING

MeSH Terms

Conditions

Lymphoma, Mantle-Cell

Interventions

orelabrutinib; Rituximab; Carmustine; Etoposide; Cytarabine; Melphalan

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; Nitrosourea Compounds; Urea; Amides; Organic Chemicals; Nitroso Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids

Central Study Contacts

Li Wang

CONTACT

+862164370045 ext 610707; 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: September 14, 2025
• First Posted: September 30, 2025
• Study Start: July 1, 2025
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): July 1, 2028
• Last Updated: September 30, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)