Bendamustine and Rituximab With or Without Orelabrutinib in MCL Treatment

NCT ID: NCT06496308

Last Updated: 2024-07-11

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

78 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-07-10

Study Completion Date

2027-07-10

Brief Summary

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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.

Detailed Description

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Conditions

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Mantle Cell Lymphoma (MCL)

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Orelabrutinib

Intervention Type DRUG

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

Bendamustine

Intervention Type DRUG

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

Rituximab

Intervention Type DRUG

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

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.

Group Type PLACEBO_COMPARATOR

Bendamustine

Intervention Type DRUG

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

Rituximab

Intervention Type DRUG

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

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.

Group Type OTHER

Orelabrutinib

Intervention Type DRUG

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

Venetoclax

Intervention Type DRUG

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

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.

Group Type OTHER

Orelabrutinib

Intervention Type DRUG

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

Interventions

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Orelabrutinib

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

Intervention Type DRUG

Bendamustine

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

Intervention Type DRUG

Rituximab

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

Intervention Type DRUG

Venetoclax

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

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Third Xiangya Hospital of Central South University

UNKNOWN

Sponsor Role collaborator

Anhui Provincial Cancer Hospital

OTHER

Sponsor Role collaborator

Fujian Medical University Union Hospital

OTHER

Sponsor Role collaborator

Yantai Yuhuangding Hospital

OTHER

Sponsor Role collaborator

Huadong Hospital Affiliated with Fudan University, Shanghai

UNKNOWN

Sponsor Role collaborator

The First Affiliated Hospital of Anhui Medical University

OTHER

Sponsor Role collaborator

Jiangxi Provincial Cancer Hospital

OTHER

Sponsor Role collaborator

Fujian Cancer Hospital

OTHER_GOV

Sponsor Role collaborator

Ruijin Hospital

OTHER

Sponsor Role lead

Responsible Party

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Zhao Weili

First Deputy Director, Hematology Department

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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Ruijin Hospital

Shanghai, , China

Site Status RECRUITING

Countries

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China

Central Contacts

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Weili Zhao

Role: CONTACT

+862164370045 ext. 610707

Li Wang

Role: CONTACT

+862164370045 ext. 610707

Facility Contacts

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Weili Zhao

Role: primary

13512112076

Other Identifiers

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ORDER

Identifier Type: -

Identifier Source: org_study_id

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