Zanubrutinib+Lenalidomide+R-ICE in Relapsed/Refractory DLBCL

Diffuse Large B-cell Lymphoma Recurrent Clinical Trial

Official title:

A Prospective, Single Arm, Open Label Study to Evaluate the Safety and Efficacy of Zanubrutinib, Lenalidomide With R-ICE Chemotherapy for Relapsed/Refractory Diffuse Large B-cell Lymphoma.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06033820
• Other study ID #: IIT-2022-0229
• Status: Recruiting
• Phase: Phase 2
• Start date: October 12, 2023
• Est. completion date: June 30, 2025

Study information

• Verified date: March 2024
• Source: RenJi Hospital
• Contact: Hong-Hui Huang, Professor
• Phone: 00862168383144
• Email: huanghonghui[@]renji.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a prospective, single center, single arm, open label study of zanubrutinib, lenalidomide in combination with Rituximab-ICE for treatment of relapsed/refractory diffuse large B-cell lymphoma.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: June 30, 2025
• Est. primary completion date: June 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Age between 18 years and 75 years 2. Histologically confirmed diagnosis of DLBCL, CD20 positive 3. Patients received at least one systemic regimens for the treatment of DLBCL, and one therapy line must have included a CD20-targeted therapy.

4. Relapsed or refractory disease 5. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. 6. Measurable disease on cross section imaging by PET and/or CT that is at least 1.5 cm in the longest diameter and measurable in two perpendicular dimensions as defined by IWG criteria.

7. Patients must meet the following laboratory criteria at screening, including:

1. Absolute neutrophil count (ANC) =1.5 x 109/L or =0.75 x 109/L if bone marrow involvement

2. Platelets =90 x 109/L or =50 x 109/L if bone marrow involvement

3. Hemoglobin =75 g/dL or =50 g/dL if bone marrow involvement

4. Total bilirubin =2.5 x upper limit of normal (ULN) unless bilirubin rise is due to Gilbert's syndrome or of hepatic involvement.

5. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) =3 x (ULN) or < 5 x ULN if hepatic involvement.

6. Creatinine Clearance Rate =60 mL/min.

7. INR =1.5 x ULN and aPTT =1.5 x ULN 8. Women of childbearing potential must have a negative serum (beta-human chorionic gonadotropin [ß-hCG]) or urine pregnancy test at Screening. Women who are pregnant or breastfeeding are ineligible for this study. Women of childbearing potential and men who are sexually active must be practicing a highly effective method of birth control during and after the study consistent with local regulations regarding the use of birth control methods for subjects participating in clinical trials. For females, these restrictions apply for 3 month after the last dose of study drug.

9. Male subject agrees to use an acceptable method for contraception for the duration of the study. Men must agree to not donate sperm during and after the study. For males, these restrictions apply for 3 months after the last dose of study drug.

10. Sign an informed consent document indicating that they understand the purpose of and procedures required for the study, and are willing to participate in the study. Must be able to adhere to study visit schedules and other protocol requirements.

Exclusion Criteria:

1. Patients who have a history of "double/triple hit" genetics. 2. Patients who have,

within 14 days prior to Day 1 dosing:

1. not discontinued CD20-targeted therapy, chemotherapy, radiotherapy, investigational anticancer therapy or other lymphoma specific therapy.

2. undergone major surgery or suffered from significant traumatic injury.

3. received live vaccines.

4. required parenteral antimicrobial therapy for active, intercurrent infections. 3. Patients who have use investigational agents within the period = 3 months prior to Day 1 dosing.

4. Patients who have,

1. Adverse events (AEs) due to previous anti-tumor therapy have not recovered

2. Known allergy or sensitivity to any drug contained in the regimen

3. have undergone ASCT within the period =3 months prior to signing the informed consent form.

4. have undergone previous allogenic stem cell transplantation.

5. have a history of deep venous thrombosis/embolism and who are not willing/able to take venous thromboembolic event prophylaxis during the entire treatment period.

6. concurrently use other anticancer or experimental treatments. 5. Coexistent second malignancy or history of prior malignancy within previous 5 years.

6. Patients who have,

1. Known history of active Hepatitis C Virus or active Hepatitis B Virus infection or any uncontrolled active systemic infection requiring intravenous (IV) antibiotics.

2. Known history of human immunodeficiency virus (HIV) infection.

3. Any significant medical or psychiatric condition that might prevent the patient from complying with all study procedures.

4. History of gastrointestinal disorder or defect that would interfere with the absorption of the study drug.

5. Patients with history of severe hemorrhagic disorders.

6. History of stroke or intracranial hemorrhage within 6 months prior to registration

Related Conditions & MeSH terms

• Diffuse Large B Cell Lymphoma Refractory
• Diffuse Large B-cell Lymphoma Recurrent
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse

Intervention

Drug:
• ZR2-ICE
Drug: zanubrutinib Oral Capsule Drug: lenalidomide Oral Capsule Drug: R-ICE chemotherapy

Locations

Country	Name	City	State
China	Renji Hospital, Shanghai Jiaotong University School of Medicine	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
RenJi Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective response rate (ORR)	To evaluate the efficacy in terms of objective response rate including CR and PR rate after three cycles of ZR2-ICE	9 weeks
Secondary	Complete remission rate (CR)	To evaluate the efficacy in terms of Complete Response Rate after three cycles of ZR2-ICE	9 weeks
Secondary	DOR	Among participants who experience an objective response, DOR is defined as the date of their first objective response (which is subsequently confirmed) to disease progression	Up to 2 years
Secondary	Progression-free survival	Progression-free survival is defined as the time from enrolment to progression or death due to any cause. The distribution of PFS will be estimated using the method of Kaplan-Meier.	Up to 2 years
Secondary	Overall survival	Overall survival is defined as the time from enrolment to death due to any cause.	Up to 2 years
Secondary	Safety Management Study	Incidence of Treatment-Emergent Adverse Events	Up to 100 days