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

• ClinicalTrials.gov Identifier: NCT05926427
• Recruitment Status: Recruiting
• First Posted: July 3, 2023
• Last Update Posted: September 5, 2023
• Sponsor: Ruijin Hospital
• Information provided by (Responsible Party): Zhao Weili, Ruijin Hospital

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 (Clinical Trial)
• Estimated Enrollment: 25 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: Single 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
• Actual Study Start Date: August 10, 2023
• Estimated Primary Completion Date: April 30, 2026
• Estimated Study Completion Date: April 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 Name: 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 :

1. Objective Response Rate (ORR) [ Time Frame: 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 :

1. 2-year Progression-Free Survival [ Time Frame: 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:

1. Overall Survival (OS) [ Time Frame: 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.
2. Complete Response (CR) Rate [ Time Frame: At the end-of-therapy response evaluation, 6 weeks after the end of Cycle 6, each cycle lasting 4 weeks ]
   The CR rate is defined as the percentage of participants with CR, on the basis of investigator assessments, according to 2014 Lugano criteria.
3. Adverse Events [ Time Frame: 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

• Ages Eligible for Study: 14 Years to 80 Years (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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.

Contacts and Locations

Contacts

Contact: Weili Zhao, Doctor; +86-64370045; zwl_trial@163.com

Contact: Li Wang, Doctor; +86-64370045; wl_wangdong@126.com

Locations

China, Shanghai

Ruijin Hospital, Shanghai Jiao Tong University School of Medicine; Recruiting

Shanghai, Shanghai, China, 200025

Contact: Weili Zhao, MD, PhD zhao.weili@yahoo.com

Sponsors and Collaborators

Ruijin Hospital

More Information

• Responsible Party: Zhao Weili, Professor, Ruijin Hospital
• ClinicalTrials.gov Identifier: NCT05926427
• Other Study ID Numbers: Oreo
• First Posted: July 3, 2023
• Last Update Posted: September 5, 2023
• Last Verified: September 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Zhao Weili, Ruijin Hospital:

CNS Lymphoma; Relapse; Refractory; orelabrutinib

Additional relevant MeSH terms:

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Rituximab; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents