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

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.

Study Overview

• Status: Recruiting
• Conditions: CNS Lymphoma
• Intervention / Treatment: Drug: Rituximab; Drug: Orelabrutinib; Drug: Chemotherapy

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 Type: Interventional
• Enrollment (Estimated): 25
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Weili Zhao, Doctor; Phone Number: +86-64370045; Email: zwl_trial@163.com
• Study Contact Backup: Name: Li Wang, Doctor; Phone Number: +86-64370045; Email: wl_wangdong@126.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200025
      • Recruiting
      • Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
      • Contact: Weili Zhao, MD, PhD; Email: zhao.weili@yahoo.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: OR-chemo; Drug: Orelabrutinib, Rituximab and recommended chemotherapy according to histopathologic type	Drug: Rituximab; 375 mg/m^2 ivgtt, D0 of each 28-day cycle; 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: Chemotherapy; Not specified, recommended regimen according to histopathologic type

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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)
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

Collaborators and Investigators

• Sponsor: Ruijin Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 10, 2023
• Primary Completion (Estimated): April 30, 2026
• Study Completion (Estimated): April 30, 2026

Study Registration Dates

• First Submitted: June 22, 2023
• First Submitted That Met QC Criteria: June 22, 2023
• First Posted (Actual): July 3, 2023

Study Record Updates

• Last Update Posted (Actual): September 5, 2023
• Last Update Submitted That Met QC Criteria: September 1, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Refractory; Relapse; CNS Lymphoma; orelabrutinib
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Rituximab
• Other Study ID Numbers: Oreo

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