B-cell Lymphoma
Conditions
Brief summary
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
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
Interventions
DRUGOrelabrutinib
Orelabrutinib, 150mg, po, qd
Sponsors
Peking University People's Hospital
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| the adverse events of Special interest | up to two years | the adverse events of Special interest: Diarrhea, atrial fibrillation/flutter, rash |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ORR | up to two years | The proportion of CR + PR in different B cell lymphoma subtype |
| DCR | up to two years | The proportion of CR + PR+SD in different B cell lymphoma subtype |
| DOR | up to two years | The time from the first remission to the first progression of the disease |
| PFS | up to two years | The time from the start of medication to the first progression of disease or death |
| OS | up to two years | The time from initiation of the drug to death from any cause |
Countries
China
Contacts
Primary ContactShenmiao Yang, Dr.
Outcome results
None listed