Efficacy and Safety of Orelabrutinib Plus Lenalidomide and Rituximab (R2) Compared to Placebo Plus R2 in r/r Marginal Zone Lymphoma

Study Overview
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Brief Summary
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Evaluate the Efficacy and Safety of Orelabrutinib Plus Lenalidomide and Rituximab (R2) Versus Placebo Plus R2 in Relapsed/Refractory Marginal Zone Lymphoma.

Official Title
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A Randomized, Controlled, Double-Blind, Phase 3 Study to Evaluate the Efficacy and Safety of Orelabrutinib Plus Lenalidomide and Rituximab (R2) Versus Placebo Plus R2 in Relapsed/Refractory Marginal Zone Lymphoma

Conditions
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Relapsed/Refractory Marginal Zone Lymphoma

Intervention / Treatment
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* Drug: Orelabrutinib
* Drug: Lenalidomide
* Drug: Rituximab
* Drug: Orelabrutinib Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years and ≤ 80 years, either sex. Histopathologically confirmed B-cell non-Hodgkin lymphoma MZL (splenic, nodal, or extra-nodal). At least one and no more than 3 prior lines of systemic therapy (CD20 targeted therapy included in at least one line). Relapsed or refractory disease. At least 1 measurable lesion confirmed through enhanced computed tomography (CT) or enhanced magnetic resonance imaging (MRI). ECOG performance status (PS) score of 0-2. Exclusion Criteria: Administration of the specified anti-tumor therapies within 2 weeks prior to the first dose of the study treatment. Administration of any other investigational product within 4 weeks prior to the first dose of the study treatment, or concurrent participation in another clinical trial. Prior treatment with any types of BTK inhibitor. Patients who are intolerant of CD20 monoclonal antibodies, or those who are resistant to lenalidomide and CD20 monoclonal antibodies. Prior allogeneic hematopoietic stem cell transplantation (Allo-HSCT), or Autologous hematopoietic stem cell transplantation (ASCT) within 6 months prior to the first dose of the study treatment; or prior CAR-T cell therapy. Central nervous system (CNS) lymphoma, and lymphoma with CNS or meningeal involvements.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Orelabrutinib<br> | Drug: Orelabrutinib<br>* Orelabrutinib Tablets<br>Drug: Lenalidomide<br>* Lenalidomide Capsules<br>Drug: Rituximab<br>* Rituximab Injection<br>|
| Placebo Comparator: Placebo<br> | Drug: Lenalidomide<br>* Lenalidomide Capsules<br>Drug: Rituximab<br>* Rituximab Injection<br>Drug: Orelabrutinib Placebo<br>* Orelabrutinib Placebo Tablets<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| IRC-assessed PFS |  | Through study completion, an average of 5 year. |