A Study of OLR in First-line Treatment of Mantle Cell Lymphoma

Study Overview
=================
Brief Summary
-----------------
This is a single-arm, multicenter, open label phase II clinical study to evaluate the efficacy and safety of OLR in the treatment of initially treated mantle cell lymphoma.

Detailed Description
-----------------
Patients initially treated with mantle cell lymphoma were screened for OLR regimen according to study admission criteria. The study will accept up to 24 cycles of treatment until disease progression or intolerable toxicity occurs and subjects voluntarily withdraw informed consent. Patients undergoing hematopoietic stem cell transplantation after complete remission may begin stem cell collection after induction therapy for at least 6 months. Twenty-nine patients are expected to be enrolled

Official Title
-----------------
A Prospective Phase II Clinical Study of Orelabrutinib in Combination With Lenalidomide and Rituximab (OLR) in First-line Treatment of Mantle Cell Lymphoma

Conditions
-----------------
Mantle Cell Lymphoma

Intervention / Treatment
-----------------
* Drug: Orelabrutinib in in combination of rituximab and lenalidomide(OLR)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histopathologically confirmed mantle cell lymphoma with chromosomal translocation. All subjects must provide adequate archived or fresh tumor tissue samples for immunohistochemistry (IHC) testing. Age 18-70, both male and female. No previous systemic treatment for lymphoma. Have at least one measurable lesion. Measurable disease was defined as measurable tumor masses ≥1.5 cm in one or both dimensions and measurable spleen lesions. Eastern Oncology Collaboration group physical status score was 0-2. Adequate hematological function Life expectancy >3 months. Have the ability to provide written informed consent and understand and comply with study requirements. Ability to adhere to research visit schedules and other protocol requirements Exclusion Criteria: Histology conformed blastolytic mantle cell lymphoma and polymorphic mantle cell lymphoma. Patients with current or suspected central nervous system involvement and history of this disease Received Bruton's tyrosine kinase inhibitor treatment Receive lenalidomide treatment Received other anti-tumor treatments Major surgery within 4 weeks prior to screening. Have a history of other active malignant diseases within 2 years prior to study entry, Systemic fungal, bacterial or viral infection with uncontrolled activity The following serological states are known for human immunodeficiency virus (HIV) infection or suggest the presence of active hepatitis B or C virus infection Clinically serious cardiovascular disease A history of severe hemorrhagic disorders, such as hemophilia A, hemophilia B, von willebrand disease, or A history of spontaneous bleeding requiring blood transfusion or other medical intervention. A history of deep vein thrombosis (DVT) or pulmonary embolism (PE) within the past 12 months. A history of major cerebrovascular disease/event, including stroke or intracranial hemorrhage, in the 6 months prior to first administration of the study drug. Anticoagulant therapy with warfarin or an equivalent vitamin K antagonist or anticoagulant therapy is required within 7 days of initial use of the study drug. Pregnant or lactating women Hypersensitivity to any study drug The presence of any life-threatening disease, medical condition, or organ system dysfunction that the investigator considers to be likely to affect the safety of the subject or cause risk

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Orelabtutinib in combination of rituximab and lenalidomide(OLR) Arm<br>Induction phase of mantle cell L lymphoma: Orelabrutinib: 150mg QD D1-28; Lenalidomide: Cycle 1: 15mg QD D1-21, if no dose-limiting toxicity occurred in Cycle 1, cycle 2-6: 20mg QD D1-21; Cycle 1: 375 mg/m2 d1, 8,15,22; Cycle 3, 5: 375 mg/m2 D1 Maintenance treatment phase: Orelabrutinib: 150mg QD D1-28; Lenalidomide: cycle 7-24: 15mg QD D1-21; Cycle 7, 9, 11, 13, 15, 17, 19, 21, 23: 375 mg/m2 D1 | Drug: Orelabrutinib in in combination of rituximab and lenalidomide(OLR)<br>* Induction treatment phase: Orelabrutinib: 150mg QD D1-28; Lenalidomide: Cycle 1: 15mg QD D1-21, if no dose-limiting toxicity occurred in Cycle 1, cycle 2-6: 20mg QD D1-21; Cycle 1: 375 mg/m2 d1, 8,15,22; Cycle 3, 5: 375 mg/m2 D1 Maintenance treatment phase: Orelabrutinib: 150mg QD D1-28; Lenalidomide: cycle 7-24: 15mg QD D1-21; Cycle 7, 9, 11, 13, 15, 17, 19, 21, 23: 375 mg/m2 D1. 28 days for a cycle.<br>* Other names: OLR Arm;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Response Rate | The proportion of patients receiving the treatment with complete remission | At the end of Cycle 6(each cycle is 28 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate | The proportion of patients with response of PR and CR. | Approximately 2 years | 
| Time to Response | Measured from the date of initiation of treatment to the time of response | Approximately 1 year | 
| The Progression Free Survival Rate in 2 Years | The proportion of patients who didn't achieve disease progression or death in 2 years. | 2 Years | 
| The Overall Survival Rate in 2 Years | The proportion of patients who didn't achieve death in 2 years | 2 Years |