Bendamustine and Rituximab With or Without Orelabrutinib in MCL Treatment

NCT06496308 | Recruiting Phase 3 DMC

• 1 other identifier: ORDER
• Study Type: interventional
• Target: 78
• Locations: 1 country
• Sites: 1

Brief Summary

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.

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 2 years)

• Overall survival

  Baseline up to data cut-off (up to approximately 2 years)

Study Arms (4)

Orelabrutinib + Bendamustine + Rituximab (OBR)

EXPERIMENTAL

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.

Drug: Orelabrutinib; Drug: Bendamustine; Drug: Rituximab

Bendamustine + Rituximab (BR)

PLACEBO COMPARATOR

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.

Drug: Bendamustine; Drug: Rituximab

Orelabrutinib + Venetoclax (OV)

OTHER

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.

Drug: Orelabrutinib; Drug: Venetoclax

Orelabrutinib (O)

OTHER

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.

Drug: Orelabrutinib

Interventions

Orelabrutinib DRUG

Orelabrutinib PO will be administered as per the schedule specified in the respective arm.

Orelabrutinib (O); Orelabrutinib + Bendamustine + Rituximab (OBR); Orelabrutinib + Venetoclax (OV)

Bendamustine DRUG

Bendamustine IV will be administered as per the schedule specified in the respective arm.

Bendamustine + Rituximab (BR); Orelabrutinib + Bendamustine + Rituximab (OBR)

Rituximab DRUG

Rituximab IV will be administered as per the schedule specified in the respective arm.

Bendamustine + Rituximab (BR); Orelabrutinib + Bendamustine + Rituximab (OBR)

Venetoclax DRUG

Venetoclax PO will be administered as per the schedule specified in the respective arm.

Orelabrutinib + Venetoclax (OV)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: 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 \> 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.

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
• The Third Xiangya Hospital of Central South University: collaborator
• Anhui Provincial Cancer Hospital: collaborator
• Fujian Medical University Union Hospital: collaborator
• Yantai Yuhuangding Hospital: collaborator
• Huadong Hospital Affiliated with Fudan University, Shanghai: collaborator
• The First Affiliated Hospital of Anhui Medical University: collaborator
• Jiangxi Provincial Cancer Hospital: collaborator
• Fujian Cancer Hospital: collaborator

Study Sites (1)

Ruijin Hospital

Shanghai, 200025, China

RECRUITING

MeSH Terms

Conditions

Lymphoma, Mantle-Cell

Interventions

orelabrutinib; Bendamustine Hydrochloride; Rituximab; venetoclax

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)

Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Weili Zhao

CONTACT

+862164370045; zhao.weili@yahoo.com

Li Wang

CONTACT

+862164370045; wl11194@rjh.com.cn

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: First Deputy Director, Hematology Department

Study Record Dates

• First Submitted: July 3, 2024
• First Posted: July 11, 2024
• Study Start: July 10, 2024
• Primary Completion (Estimated): July 10, 2027
• Study Completion (Estimated): July 10, 2027
• Last Updated: July 11, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)