Orelabrutinib Plus Rituximab Followed by Maintenance With Orelabrutinib for Relapsed and Refractory Follicular Lymphoma(RR FL)

Study Overview
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Brief Summary
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This phase 2 trial studies the efficacy and safety of orelabrutinib plus rituximab followed by maintenance with orelabrutinib for relapsed and refractory follicular lymphoma(RR FL)

Official Title
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Orelabrutinib Plus Rituximab Followed by Maintenance With Orelabrutinib for Relapsed and Refractory Follicular Lymphoma(RR FL) ：a Single Arm, Open Label, Multi-center Phase II Study

Conditions
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Follicular Lymphoma, Relapsed and Refractory Follicular Lymphoma

Intervention / Treatment
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* Drug: Orelabrutinib and Rituximab
* Drug: Orelabrutinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed grade 1, 2, or 3A FL; Patients received prior anti-lymphoma treatment; At least one evaluable lesion according to 2014 Lugano criteria; Age 18 years or older; Eastern Cooperative Oncology Group (ECOG) of 0-2; Life expectancy > 3 months; Able to participate in all required study procedures; Proper functioning of the major organs: Exclusion Criteria: Patients who required warfarin or had a history of stroke or intracranial hemorrhage within 6 months, active transformed disease; Histological transformation of follicular lymphoma; Known central nervous system lymphoma; Received a prior allogeneic hematopoietic stem cell transplant. Prior autologous hematopoietic stem cell transplant is allowed; Subjects who have received prior treatment with ibrutinib, or other BTK inhibitors; Uncontrolled active infection, with the exception of tumor-related B symptom fever; Prior nitrosoureas within 6 weeks, chemotherapy within 3 weeks, therapeutic anticancer antibodies within 4 weeks, radio- or toxin-immunoconjugates within 10 weeks, radiation therapy or other investigational agents within 3 weeks, or major surgery within 4 weeks of first dose of study drug; Subjects who progressed or become refractory while on treatment with PI3K inhibitors are excluded. However, subjects who were responding to PI3K inhibitors, but had treatment discontinued due to toxicity, are eligible; Patients require treatment with strong CYP3A inhibitors; Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of Screening; Patients with active hepatitis B or active hepatitis C. Patients who are positive for hepatitis B Surface Antigen (HBsAg) or hepatitis C Virus (HCV) antibodies at screening stage must pass further detection of hepatitis B Virus (HBV) DNA (no more than 1000 IU/mL) and HCV RNA (no more than the lower limit of the detection method) in the row. Hepatitis B carriers, stable hepatitis B (DNA titer should not be higher than 1000 IU/mL) after drug treatment, and cured hepatitis C patients can be enrolled in the group;

Ages Eligible for Study
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Minimum Age: 18 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Orelabrutinib plus Rituximab followed by Maintenance with Orelabrutinib<br>Induction therapy: Patients receive Orelabrutinib at a dose of 25 mg once daily on days 1-28 and rituximab at a dose of 375mg/m2 on day 1. Treatment cycles repeat every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. If patients achieve CR or PR or SD, they will be treated with maintenance therapy Maintenance therapy: Patients receive Orelabrutinib every day at a dose of 150mg for up to two years in the absence of disease progression or unacceptable toxicity. | Drug: Orelabrutinib and Rituximab<br>* Orelabrutinib 150mg po qd d1-28; Rituximab 375mg/m2 iv.drip d1.<br>* Other names: induction treatment;Drug: Orelabrutinib<br>* Orelabrutinib 150mg po qd<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response rate | Objective Response rate will be determined on the basis of investigator assessments according to 2014 Lugano criteria. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete remission rate | Complete remission rate will be determined on the basis of investigator | 2 years | 
| Progression Free Survival | The time from the start of treatment to the progression of the tumor or death (due to any cause). | 4 years | 
| Overall Survival | The time from the start of treatment to time of death (due to any cause). | 4 years | 
| Duration of Response | The time from the first assessment of complete remission or partial remission to progressive disease or death (due to any cause). | 4 years | 
| Percentage of Participants With Adverse Events | Adverse Events will be determined and graded on the basis of investigator assessments according to NCI CTC AE 5.0 | 4 years |