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

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

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

Study Overview

• Status: Recruiting
• Conditions: B-cell Lymphoma
• Intervention / Treatment: Drug: Orelabrutinib

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

• Study Type: Observational
• Enrollment (Estimated): 30

Contacts and Locations

• Study Contact: Name: Shenmiao Yang, Dr.; Phone Number: 8601088326666; Email: yangshenmiao@hotmail.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100044
      • Recruiting
      • Deparment of Hematology, Peking University People's Hospital
      • Contact: Xiaojun Huang, doctor; Phone Number: 8601088326666; Email: xjrm@medmail.com.cn
      • Principal Investigator: Shenmiao Yang, Dr.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

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

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Orelabrutinib; 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; Orelabrutinib, 150mg, po, qd; Other Names: ICP-022

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Peking University People's Hospital
• Investigators: Principal Investigator: Shenmiao Yang, Peking university People's Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): November 10, 2023
• Primary Completion (Estimated): December 10, 2024
• Study Completion (Estimated): March 10, 2025

Study Registration Dates

• First Submitted: August 9, 2022
• First Submitted That Met QC Criteria: August 9, 2022
• First Posted (Actual): August 10, 2022

Study Record Updates

• Last Update Posted (Actual): October 26, 2023
• Last Update Submitted That Met QC Criteria: October 24, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell
• Other Study ID Numbers: intolerant to BTK inhibitors

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No