Orelabrutinib Combined With Rituximab and Chemotherapy for Relapsed/Refractory B-Cell Lymphoma Patients With Central Nervous System Involvement

CNS Lymphoma Clinical Trial

Official title:

Orelabrutinib Combined With Rituximab and Chemotherapy for Relapsed/Refractory B-Cell Lymphoma Patients With Central Nervous System Involvement

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05926427
• Other study ID #: Oreo
• Status: Recruiting
• Phase: Phase 2
• Start date: August 10, 2023
• Est. completion date: April 30, 2026

Study information

• Verified date: September 2023
• Source: Ruijin Hospital
• Contact: Weili Zhao, Doctor
• Phone: +86-64370045
• Email: zwl_trial[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This single-center, open, single-arm study aim to evaluate the efficacy and tolerability of a therapy introducing orelabrutinib on the basis of rituximab and chemotherapy in treating patients with relapsed or refractory B-cell lymphoma invloving central nervous system.

Description:

Participants will receive orelabrutinib in addition to second-line therapy consisting of rituximab and recommended chemotherapy according to histopathologic type. After treatment of 6 cycles with the new regimen, the patients achieving CR or PR would go on to receive autologous haematopoietic stem cell transplantation (auto-HSCT) with or without orelabrutinib maintenance of 2 years (if tolerable) or orelabrutinib maintenance alone if intolerant to auto-HSCT.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 25
• Est. completion date: April 30, 2026
• Est. primary completion date: April 30, 2026
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 14 Years to 80 Years

Eligibility

Inclusion Criteria:

• 14 to 80 years old;
• Histopathologically confirmed CD20 positive B-cell lymphoma according to the 5th edition of the World Health Organization (WHO) Classification of Haematolymphoid Tumours;
• After systemic treatment of the CNS lesions;
• Life expectancy of > 3 months (in the opinion of the investigator);
• No non-haematologic adverse events, except alopecia, higher than grade 1 according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0;
• Absolute Neutrophil Count (ANC) = 1.0×10^9/L, Platelet Count = 50×10^9/L and Haemoglobin = 60 g/L, without transfusion or any use of pharmacologically hematopoietic drugs in 2 weeks;
• Serum Creatinine (SCr) = 1.5 times the Upper Limit of Normal (ULN) or Creatinine Clearance Rate (CCR) = 30 mL/min;
• Serum total Bilirubin (tBil) = 1.5 × ULN and both Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) = 2.5 × ULN without hepatic metastases, otherwise tBil = 3 × ULN and AST, ALT = 5 × ULN respectively;
• International Normalized Ratio (INR) = 1.5 and activated Partial Thromboplastin Time (aPTT) = 1.5 × ULN;
• Left Ventricular Ejection Fraction (LVEF) = 50%;
• Agreeing to provide written informed consent prior to any special examination or procedure for the research on their own or legal representative.

Exclusion Criteria:

• Pregnant or lactating women;
• Known Hepatitis B Virus (HBV) and/or Hepatitis C Virus (HCV) infection (HBV infection refers to HBV-DNA > detectable limit);
• With acquired or congenital immunodeficiency;
• With congestive heart failure in 6 months before enrollment, New York Heart Association (NYHA) heart function class III or IV, or LVEF < 50%;
• Known to be allergic to the test drug ingredients;
• Diagnosed with or being treated for malignancy other than lymphoma;
• With severe infection;
• Substance abuse, medical, psychological, or social conditions that may interfere with the subjects' participation in the study or evaluation of the study results;
• Deemed unsuitable for the group.

Related Conditions & MeSH terms

• CNS Lymphoma
• Lymphoma

Intervention

Drug:
• Orelabrutinib
150 mg qd po, until disease progression, intolerance of drug toxicity or death, otherwise maintaining during 2 years of follow-up
• Rituximab
375 mg/m^2 ivgtt, D0 of each 28-day cycle
• Chemotherapy
Not specified, recommended regimen according to histopathologic type

Locations

Country	Name	City	State
China	Ruijin Hospital, Shanghai Jiao Tong University School of Medicine	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Ruijin Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Overall Survival (OS)	Overall survival is defined as the time from the date of first treatment to the date of death from any cause.	Baseline up to data cut-off (up to approximately 2 years)
Other	Complete Response (CR) Rate	The CR rate is defined as the percentage of participants with CR, on the basis of investigator assessments, according to 2014 Lugano criteria.	At the end-of-therapy response evaluation, 6 weeks after the end of Cycle 6, each cycle lasting 4 weeks
Other	Adverse Events	Any harmful reaction that occurs during the treatment of a disease according to the normal usage and dosage of a drug, which is unrelated to the purpose of treatment.	Baseline up to data cut-off (up to approximately 2 years)
Primary	Objective Response Rate (ORR)	The ORR is defined as percentage of participants with overall response including complete response (CR) and partial response (PR), on the basis of investigator assessments, according to 2014 Lugano criteria.	At the end-of-therapy response evaluation, 6 weeks after the end of Cycle 6, each cycle lasting 4 weeks
Secondary	2-year Progression-Free Survival	Progression-free survival was defined as the time from the date of first treatment until the date of the first documented day of disease progression or relapse, according to 2014 Lugano criteria, or death from any cause, whichever occurred first.	2 years