Clinical trial NCT05926427: Orelabrutinib Combined With Rituximab and Chemotherapy for Relapsed/Refractory B-Cell Lymphoma Patients With Central Nervous System Involvement
Official title: Orelabrutinib Combined With Rituximab and Chemotherapy for Relapsed/Refractory B-Cell Lymphoma Patients With Central Nervous System Involvement
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: CNS Lymphoma
Keywords: CNS Lymphoma
Relapse
Refractory
orelabrutinib
Lead sponsor: Ruijin Hospital
Sponsor class: OTHER
First posted: 2023-07-03
Enrollment: 25
Sex: ALL
Minimum age (years): 14
Maximum age (years): 80
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Single Group
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: At the end-of-therapy response evaluation, 6 weeks after the end of Cycle 6, each cycle lasting 4 weeks
Secondary outcomes:
measure: 2-year Progression-Free Survival
timeFrame: 2 years
Other outcomes:
measure: Overall Survival (OS)
timeFrame: Baseline up to data cut-off (up to approximately 2 years)
measure: Complete Response (CR) Rate
timeFrame: At the end-of-therapy response evaluation, 6 weeks after the end of Cycle 6, each cycle lasting 4 weeks
measure: Adverse Events
timeFrame: Baseline up to data cut-off (up to approximately 2 years)
Locations:
city: Shanghai
country: China
facility: Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
state: Shanghai
Study officials:
References: