Orelabrutinib Therapy in Patients With r/r B-cell Lymphoma Intolerant to Other Bruton Tyrosine Kinase Inhibitors

Study Overview
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Brief Summary
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To evaluate the safety and effecacy of Orelabrutinib therapy in patients with relapsed or refractory B-cell lymphoma (including R /rCLL/SLL and R /rMCL) who are intolerant to ibrutinib/zanubrutinib or other BTK inhibitors

Detailed Description
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The efficacy of first-generation BTKi ibrutinib in the treatment of B-cell lymphoma is reasonable, but the kinase selectivity is poor and the off-target effect is increased. It is associated with non-BTK-related adverse reactions such as bleeding, atrial fibrillation, diarrhea and rash.This is the reason why some patients stop taking BTKi and cannot benefit from long-term treatment. Orelabrutinib kinase is highly selective. The safety of the treatment of 266 Chinese patients with B-cell malignancies (including r/r CLL/SLL, r/r MCL, r/r WM, r/r MZL, r/r CNSL) showed that no ≥ grade 3 atrial fibrillation occurred.The incidence of grade 3 diarrhea and severe bleeding adverse events was lower than that of ibrutinib and zanubrutinib.Therefore, the aim of this study was to evaluate the safety and efficacy of self-selected switching to obrutinib in patients with relapsed or refractory B-cell lymphoma intolerant to ibrutinib/zanubrutinib therapy

Official Title
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Observational Study of Orelabrutinib Therapy in Patients With Relapsed or Refractory B-cell Lymphoma Intolerant to Other Bruton Tyrosine Kinase Inhibitors

Conditions
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B-cell Lymphoma

Intervention / Treatment
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* Drug: Orelabrutinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1) Age ≥18 years, both sexes; 2) Confirmed by the following diagnostic criteria CLL/SLL: relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma confirmed by flow cytometry or histopathology according to iwCLL2018 criteria MCL: Recurrent or refractory mantle cell lymphoma histopathologically confirmed: including cytogenetic testing T (11;14) Mantle cell lymphoma with positive/high immunohistochemical expression of Cyclin D1 3) Previous treatment with ibrutinib/zanubrutinib/or other BTK inhibitors and any of the following conditions were defined by the investigator as poor tolerance to ibrutinib/zanubrutinib or other BTK inhibitors: A) Grade ≥2 nonhematologic toxicity lasting >7 days with or without treatment; B) any non-hematological toxicity of ≥ grade 3 ; C) Grade 3 neutropenia with infection or fever; D) Grade 4 hematologic toxicity that persisted until the investigator chose to discontinue ibrutinib/ zanubrutinib or other BTK inhibitors due to toxicity rather than disease progression 4) The investigator-initiated treatment decision to use Orelabrutinib (before study enrollment); 5) Life expectancy ≥3 months; 6) The patient or his or her legal representative voluntarily signed written informed consent Exclusion Criteria: 1) Richter conversion (CLL/SLL) or disease progression during treatment with ibrutinib/ zanubrutinib or other BTK inhibitors; 2) Past treatment with Orelabrutinib; 3) Absolute neutrophil ANC<0.75×109/L, platelet PLT<50×109/L; 4) Blood biochemistry: total bilirubin (TBIL) >2 times the upper limit of normal ULN (unless Gilbert syndrome is diagnosed), AST or ALT>2.5× ULN; Serum creatinine (Cr) >1.5×ULN 5) Coagulation function: INR and APTT ≤1.5 × ULN; 6) Grade 3 or 4 adverse events related to ongoing unresponded treatment with ibrutinib/ zanubrutinib or other BTK inhibitors 7) Participate in research projects that use interventions outside the scope of routine clinical practice

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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Orelabrutinib<br>Patients with relapsed or refractory B-cell lymphoma (including r/rCLL/SLL, r/rMCL) intolerant to ibrutinib/zanubrutinib or other BTK inhibitors who have decided to receive Orelabrutinib therapy | Drug: Orelabrutinib<br>* Orelabrutinib, 150mg, po, qd<br>* Other names: ICP-022;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the adverse events of Special interest | the adverse events of Special interest: Diarrhea, atrial fibrillation/flutter, rash | up to two years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR | The proportion of CR + PR in different B cell lymphoma subtype | up to two years | 
| DCR | The proportion of CR + PR+SD in different B cell lymphoma subtype | up to two years | 
| DOR | The time from the first remission to the first progression of the disease | up to two years | 
| PFS | The time from the start of medication to the first progression of disease or death | up to two years | 
| OS | The time from initiation of the drug to death from any cause | up to two years |