Evaluating Different Doses of Orelabrutinib in MCL

Study Overview
=================
Brief Summary
-----------------
This is A Randomized,Open-label, Multicenter, Phase II Trial Evaluating Two Different Doses of Orelabrutinib in Mantle Cell Lymphoma to Evaluate the Efficacy and Safety in Mantle Cell Lymphoma.

Official Title
-----------------
A Randomized,Open-label, Multicenter, Phase II Trial Evaluating Two Different Doses of Orelabrutinib in Mantle Cell Lymphoma

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

Intervention / Treatment
-----------------
* Drug: Orelabrutinib High dose
* Drug: Orelabrutinib Low dose


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male and female subjects ≥ 18 years of age. Mantle cell lymphoma (MCL) confirmed by histopathology. Subjects who have not previously received standard systemic care and relapsing/refractory subjects who have previously received standard systemic care. At least one measurable lesion. ECOG Physical fitness score 0-2 points. Expected survival time ≥ 4 months. Full hematology function. Blood clotting function is basically normal. Subjects with basically normal liver, kidney and heart function. Subject voluntarily signs a written ICF. The serum pregnancy test of female subjects with fertility potential was negative within 7 days before the first dosing. Female subjects with reproductive potential or male subjects and their partners must agree to use effective contraception for at least 6 months from signing the ICF until the last dose of the study drug. Exclusion Criteria: Adequate treatment with BTK inhibitors. Have a history of severe allergic disease and a history of severe drug allergy. Subjects who have received the treatment or drug restricted in the protocol within the time specified for the first use of the investigational drug. The last use of a potent CYP3A inhibitor or potent CYP3A inducer (including food, western medicine, and Chinese medicine) was less than 2 weeks (or less than 5 half-lives, depending on the time) from the first trial, or plan to take a potent CYP3A inhibitor or potent CYP3A inducer drug or food during the study period. History of other active malignant diseases within 2 years prior to screening. Subjects with systemic bacterial, viral, fungal (other than nail fungal infections) or parasitic infections with poorly controlled activity. Indicates active hepatitis B or C virus infection. There are diseases that are excluded from the criteria in the programme. Toxicity of previous anticancer therapy was still ≥ grade 2 at the start of study therapy (according to CTCAE V5.0). History of severe bleeding disorder. People with a known history of alcohol or drug abuse. Subjects with mental disorders or poor compliance. Pregnant or lactating female subjects. Other conditions deemed unsuitable for participation in this study by the investigator.

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

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

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

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

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Orelabrutinib high dose<br> | Drug: Orelabrutinib High dose<br>* Orelabrutinib will be administered as 3 tablets once per day<br>|
| Experimental: Orelabrutinib low dose<br> | Drug: Orelabrutinib Low dose<br>* Orelabrutinib will be administered as 1 tablet once per day<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate（ORR） | Proportion of subjects with tumor response of Complete Response（CR） or Partial Response（PR） after treatment in total subjects. | Through study completion, an average of 2 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Response Rate （CRR） | The proportion of subjects with tumor response of Complete Response（CR） after treatment in total subjects. | Through study completion, an average of 2 year | 
| Progression-Free Survival (PFS) | From date of randomization until the date of first documented progression or date of death from any cause, whichever came first. | Through study completion, an average of 2 year | 
| Duration of Response (DoR) | The time from documentation of objective response to the first occurrence of tumor progression or death due to any cause, whichever occurs first. | Through study completion, an average of 2 year | 
| Maximum concentration (Cmax,ss) |  | Predose up to 24 hours postdose | 
| Time to maximum concentration (Tmax) |  | Predose up to 24 hours postdose | 
| Area under the plasma concentration-time curve (AUC) |  | Predose up to 24 hours postdose | 
| Half-life (T1/2) |  | Predose up to 24 hours postdose | 
| Apparent clearance (CL/F) |  | Predose up to 24 hours postdose | 
| Adverse events（AEs） |  | Through study completion, an average of 2 year | 
| Serious adverse events （SAEs） |  | Through study completion, an average of 2 year |