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

Sponsor

Ruijin Hospital (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05926427

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

0.7

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
CNS Lymphoma	Drug: Orelabrutinib Drug: Rituximab Drug: Chemotherapy	Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

25 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

Single GroupSingle Group

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Jul 1, 2023

Anticipated Primary Completion Date :

Apr 30, 2026

Anticipated Study Completion Date :

Apr 30, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: OR-chemo Drug: Orelabrutinib, Rituximab and recommended chemotherapy according to histopathologic type	Drug: Orelabrutinib 150 mg qd po, until disease progression, intolerance of drug toxicity or death, otherwise maintaining during 2 years of follow-up Other Names: ICP-022 Drug: Rituximab 375 mg/m^2 ivgtt, D0 of each 28-day cycle Drug: Chemotherapy Not specified, recommended regimen according to histopathologic type

Arm

Intervention/Treatment

Experimental: OR-chemo

Drug: Orelabrutinib, Rituximab and recommended chemotherapy according to histopathologic type

Drug: Orelabrutinib

150 mg qd po, until disease progression, intolerance of drug toxicity or death, otherwise maintaining during 2 years of follow-up

Other Names:

ICP-022

Drug: Rituximab

375 mg/m^2 ivgtt, D0 of each 28-day cycle

Drug: Chemotherapy

Not specified, recommended regimen according to histopathologic type

Outcome Measures

Primary Outcome Measures

Objective Response Rate (ORR) [Approximately 6 weeks after last dose of Cycle 6]
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

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.

Other Outcome Measures

Overall Survival (OS) [Baseline up to data cut-off (up to approximately 2 years)]
Overall survival is defined as the time from the date of first treatment to the date of death from any cause.
Complete Response (CR) Rate [Approximately 6 weeks after last dose of Cycle 6]
The CR rate is defined as the percentage of participants with CR, on the basis of investigator assessments, according to 2014 Lugano criteria.
Adverse Events [Baseline up to data cut-off (up to approximately 2 years)]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

14 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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.