Bendamustine and Rituximab With or Without Orelabrutinib in MCL Treatment

July 3, 2024 updated by: Zhao Weili, Ruijin Hospital

A Multicenter, Open-label, Randomized Controlled Study of Orelabrutinib in Combination With Bendamustine and Rituximab Versus Bendamustine and Rituximab in the Treatment of Transplant-Ineligible, Intermediate- to High-Risk Mantle Cell Lymphoma (MCL)

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

78

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
      • Shanghai, China, 200025
        • Recruiting
        • Ruijin Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Orelabrutinib + Bendamustine + Rituximab (OBR)
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
Orelabrutinib PO will be administered as per the schedule specified in the respective arm.
Drug: Bendamustine
Bendamustine IV will be administered as per the schedule specified in the respective arm.
Drug: Rituximab
Rituximab IV will be administered as per the schedule specified in the respective arm.
Placebo Comparator: Bendamustine + Rituximab (BR)
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
Bendamustine IV will be administered as per the schedule specified in the respective arm.
Drug: Rituximab
Rituximab IV will be administered as per the schedule specified in the respective arm.
Other: Orelabrutinib + Venetoclax (OV)
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
Orelabrutinib PO will be administered as per the schedule specified in the respective arm.
Drug: Venetoclax
Venetoclax PO will be administered as per the schedule specified in the respective arm.
Other: Orelabrutinib (O)
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
Orelabrutinib PO will be administered as per the schedule specified in the respective arm.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Complete response rate
Time Frame: End of induction treatment visit (6-8 weeks after last dose on Day 1 of Cycle 6 [Cycle length=28 days]
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival
Time Frame: Baseline up to data cut-off (up to approximately 2 years)
Overall survival was defined as the time from the date of randomization to the date of death from any cause.
Baseline up to data cut-off (up to approximately 2 years)
Progression-free survival
Time Frame: Baseline up to data cut-off (up to approximately 2 years)
Progression-free survival was defined as the time from the date of randomization until the date of the first documented day of disease progression or relapse, using 2014 Lugano criteria, or death from any cause, whichever occurred first.
Baseline up to data cut-off (up to approximately 2 years)
Overall Response Rate
Time Frame: End of induction treatment visit (6-8 weeks after last dose on Day 1 of Cycle 6 [Cycle length=28 days]
Percentage of participants with overall 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]

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Ruijin Hospital

Collaborators

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

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

July 10, 2024

Primary Completion (Estimated)

July 10, 2027

Study Completion (Estimated)

July 10, 2027

Study Registration Dates

First Submitted

July 3, 2024

First Submitted That Met QC Criteria

July 3, 2024

First Posted (Actual)

July 11, 2024

Study Record Updates

Last Update Posted (Actual)

July 11, 2024

Last Update Submitted That Met QC Criteria

July 3, 2024

Last Verified

July 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ORDER

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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