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

B-cell Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05495828
• Other study ID #: intolerant to BTK inhibitors
• Status: Recruiting
• Start date: November 10, 2023
• Est. completion date: March 10, 2025

Study information

• Verified date: October 2023
• Source: Peking University People's Hospital
• Contact: Shenmiao Yang, Dr.
• Phone: 8601088326666
• Email: yangshenmiao[@]hotmail.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: March 10, 2025
• Est. primary completion date: December 10, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• B-cell Lymphoma
• Lymphoma
• Lymphoma, B-Cell

Intervention

Drug:
• Orelabrutinib
Orelabrutinib, 150mg, po, qd

Locations

Country	Name	City	State
China	Deparment of Hematology, Peking University People's Hospital	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Peking University People's Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	the adverse events of Special interest	the adverse events of Special interest: Diarrhea, atrial fibrillation/flutter, rash	up to two years
Secondary	ORR	The proportion of CR + PR in different B cell lymphoma subtype	up to two years
Secondary	DCR	The proportion of CR + PR+SD in different B cell lymphoma subtype	up to two years
Secondary	DOR	The time from the first remission to the first progression of the disease	up to two years
Secondary	PFS	The time from the start of medication to the first progression of disease or death	up to two years
Secondary	OS	The time from initiation of the drug to death from any cause	up to two years