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

Phase 2

Recruiting

• Conditions: CNS Lymphoma
• Interventions: Drug: Orelabrutinib; Drug: Rituximab; Drug: Chemotherapy

• Registration Number: NCT05926427
• Lead Sponsor: Ruijin Hospital

Brief 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.

Detailed 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.

Study Timeline

• Study First Submitted: 2023-06-22
• Study First Submitted QC: 2023-06-22
• Study First Posted: 2023-07-03
• Study Start: 2023-08-10
• Status Verified: 2023-09
• Last Update Submitted: 2023-09-01
• Last Update Posted: 2023-09-05
• Primary Completion: 2026-04-30
• Study Completion: 2026-04-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 25

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
OR-chemo	Chemotherapy	Drug: Orelabrutinib, Rituximab and recommended chemotherapy according to histopathologic type
OR-chemo	Orelabrutinib	Drug: Orelabrutinib, Rituximab and recommended chemotherapy according to histopathologic type
OR-chemo	Rituximab	Drug: Orelabrutinib, Rituximab and recommended chemotherapy according to histopathologic type

Primary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR)	At the end-of-therapy response evaluation, 6 weeks after the end of Cycle 6, each cycle lasting 4 weeks	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.

Secondary Outcome Measures

Name	Time	Method
2-year Progression-Free Survival	2 years	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.

Trial Locations

Locations (1)

Ruijin Hospital, Shanghai Jiao Tong University School of Medicine; 🇨🇳 Shanghai, Shanghai, China