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

Primary Purpose

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

Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
ZR2-ICE
Sponsored by
RenJi Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diffuse Large B-cell Lymphoma Recurrent focused on measuring diffuse large B-cell lymphoma, Zanubrutinib, Lenalidomide, Salvage therapy

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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: Absolute neutrophil count (ANC) ≥1.5 x 109/L or ≥0.75 x 109/L if bone marrow involvement Platelets ≥90 x 109/L or ≥50 x 109/L if bone marrow involvement Hemoglobin ≥75 g/dL or ≥50 g/dL if bone marrow involvement Total bilirubin ≤2.5 x upper limit of normal (ULN) unless bilirubin rise is due to Gilbert's syndrome or of hepatic involvement. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) ≤3 x (ULN) or < 5 x ULN if hepatic involvement. Creatinine Clearance Rate ≥60 mL/min. 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 [β-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: not discontinued CD20-targeted therapy, chemotherapy, radiotherapy, investigational anticancer therapy or other lymphoma specific therapy. undergone major surgery or suffered from significant traumatic injury. received live vaccines. 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, Adverse events (AEs) due to previous anti-tumor therapy have not recovered Known allergy or sensitivity to any drug contained in the regimen have undergone ASCT within the period ≤3 months prior to signing the informed consent form. have undergone previous allogenic stem cell transplantation. 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. concurrently use other anticancer or experimental treatments. 5. Coexistent second malignancy or history of prior malignancy within previous 5 years. 6. Patients who have, Known history of active Hepatitis C Virus or active Hepatitis B Virus infection or any uncontrolled active systemic infection requiring intravenous (IV) antibiotics. Known history of human immunodeficiency virus (HIV) infection. Any significant medical or psychiatric condition that might prevent the patient from complying with all study procedures. History of gastrointestinal disorder or defect that would interfere with the absorption of the study drug. Patients with history of severe hemorrhagic disorders. History of stroke or intracranial hemorrhage within 6 months prior to registration

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    ZR2-ICE Group

    Arm Description

    All patients will receive 3 cycles of ZR2-ICE immunochemotherapy every three weeks.

    Outcomes

    Primary Outcome Measures

    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

    Secondary Outcome Measures

    Complete remission rate (CR)
    To evaluate the efficacy in terms of Complete Response Rate after three cycles of ZR2-ICE
    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
    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.
    Overall survival
    Overall survival is defined as the time from enrolment to death due to any cause.
    Safety Management Study
    Incidence of Treatment-Emergent Adverse Events

    Full Information

    First Posted
    September 5, 2023
    Last Updated
    September 28, 2023
    Sponsor
    RenJi Hospital
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    1. Study Identification

    Unique Protocol Identification Number
    NCT06033820
    Brief Title
    Zanubrutinib+Lenalidomide+R-ICE in Relapsed/Refractory DLBCL
    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.
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    September 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    October 1, 2023 (Anticipated)
    Primary Completion Date
    June 30, 2025 (Anticipated)
    Study Completion Date
    June 30, 2025 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    RenJi Hospital

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Product Manufactured in and Exported from the U.S.
    No

    5. Study Description

    Brief 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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Diffuse Large B-cell Lymphoma Recurrent, Diffuse Large B Cell Lymphoma Refractory
    Keywords
    diffuse large B-cell lymphoma, Zanubrutinib, Lenalidomide, Salvage therapy

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    20 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    ZR2-ICE Group
    Arm Type
    Experimental
    Arm Description
    All patients will receive 3 cycles of ZR2-ICE immunochemotherapy every three weeks.
    Intervention Type
    Drug
    Intervention Name(s)
    ZR2-ICE
    Intervention Description
    Drug: zanubrutinib Oral Capsule Drug: lenalidomide Oral Capsule Drug: R-ICE chemotherapy
    Primary Outcome Measure Information:
    Title
    Objective response rate (ORR)
    Description
    To evaluate the efficacy in terms of objective response rate including CR and PR rate after three cycles of ZR2-ICE
    Time Frame
    9 weeks
    Secondary Outcome Measure Information:
    Title
    Complete remission rate (CR)
    Description
    To evaluate the efficacy in terms of Complete Response Rate after three cycles of ZR2-ICE
    Time Frame
    9 weeks
    Title
    DOR
    Description
    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
    Time Frame
    Up to 2 years
    Title
    Progression-free survival
    Description
    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.
    Time Frame
    Up to 2 years
    Title
    Overall survival
    Description
    Overall survival is defined as the time from enrolment to death due to any cause.
    Time Frame
    Up to 2 years
    Title
    Safety Management Study
    Description
    Incidence of Treatment-Emergent Adverse Events
    Time Frame
    Up to 100 days

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    75 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    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: Absolute neutrophil count (ANC) ≥1.5 x 109/L or ≥0.75 x 109/L if bone marrow involvement Platelets ≥90 x 109/L or ≥50 x 109/L if bone marrow involvement Hemoglobin ≥75 g/dL or ≥50 g/dL if bone marrow involvement Total bilirubin ≤2.5 x upper limit of normal (ULN) unless bilirubin rise is due to Gilbert's syndrome or of hepatic involvement. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) ≤3 x (ULN) or < 5 x ULN if hepatic involvement. Creatinine Clearance Rate ≥60 mL/min. 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 [β-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: not discontinued CD20-targeted therapy, chemotherapy, radiotherapy, investigational anticancer therapy or other lymphoma specific therapy. undergone major surgery or suffered from significant traumatic injury. received live vaccines. 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, Adverse events (AEs) due to previous anti-tumor therapy have not recovered Known allergy or sensitivity to any drug contained in the regimen have undergone ASCT within the period ≤3 months prior to signing the informed consent form. have undergone previous allogenic stem cell transplantation. 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. concurrently use other anticancer or experimental treatments. 5. Coexistent second malignancy or history of prior malignancy within previous 5 years. 6. Patients who have, Known history of active Hepatitis C Virus or active Hepatitis B Virus infection or any uncontrolled active systemic infection requiring intravenous (IV) antibiotics. Known history of human immunodeficiency virus (HIV) infection. Any significant medical or psychiatric condition that might prevent the patient from complying with all study procedures. History of gastrointestinal disorder or defect that would interfere with the absorption of the study drug. Patients with history of severe hemorrhagic disorders. History of stroke or intracranial hemorrhage within 6 months prior to registration
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Hong-Hui Huang, Professor
    Phone
    00862168383144
    Email
    huanghonghui@renji.com

    12. IPD Sharing Statement

    Plan to Share IPD
    No

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

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