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Chidamide Combined With Azacitidine and Mitoxantrone Liposome in the Treatment of Relapsed/Refractory (nTFHL)

Primary Purpose

T Cell Lymphoma

Status
Not yet recruiting
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
Cidapenem combined with azacitidine and mitoxantrone liposome (CAM) regimen
Sponsored by
The First Affiliated Hospital with Nanjing Medical University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for T Cell Lymphoma

Eligibility Criteria

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

Inclusion Criteria: R/R nTFHL confirmed by pathological tissue, with diagnostic criteria referring to the 2022 WHO diagnostic criteria. Patients who have undergone at least one previous systemic treatment (including chemotherapy, HSCT, etc.) without remission or relapse after remission. Signed written informed consent and who are able to comply with the visits and related procedures specified in the protocol. whole-body PET/CT performed 28 days prior to study entry, which must have at least 1 evaluable or measurable lesion meeting Lugano 2014 criteria: lymph node lesions, measurable lymph nodes need to be >1.5 cm in length; non-lymphoid lesions, measurable extra-nodal lesions need to be >1.0 cm in length. with a PS score of 0 to 2 according to ECOG with adequate organ and bone marrow function, defined as follows: neutrophil count ≥ 1.5×109/L, platelet count ≥ 75×109/L, and hemoglobin ≥ 80 g/L (relaxed to ≥ 1.0×109/L for neutrophil count, ≥ 50×109/L for platelet count, and ≥ 75 g/L for hemoglobin in patients with bone marrow involvement); Liver and kidney function: serum creatinine (Cr) ≤ 1.5 times the upper limit of normal value; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 times the upper limit of normal value (≤ 5 times the upper limit of normal value for patients with liver invasion); total bilirubin (TBIL) ≤ 1.5 times the upper limit of normal value (≤ 3 times the upper limit of normal value for patients with liver invasion); life expectancy of more than 3 months age 18 to 75 years. Exclusion Criteria: Subjects with a history of prior antitumor therapy that is one of the following. Previous recipients of mitoxantrone or mitoxantrone liposomes. Prior treatment with doxorubicin or other anthracyclines with a total cumulative dose of doxorubicin > 360 mg/m2 (other anthracyclines converted to 1 mg doxorubicin equivalent to 2 mg epirubicin). Patients who have received autologous hematopoietic stem cell transplantation (ASCT) within 100 days of the first dose, or who have received allogeneic hematopoietic stem cell transplantation. have received antitumor therapy (including chemotherapy, targeted therapy, hormonal therapy, administration of herbal medicine with antitumor activity, etc.) or participated in other clinical trials and received clinical trial medication within 4 weeks prior to the first administration of this study drug. Hypersensitivity reaction to any investigational drug or its components. Uncontrollable systemic disease (e.g., progressive infection, uncontrollable hypertension, diabetes mellitus, etc.). Cardiac function and disease consistent with one of the following. Long QTc syndrome or QTc interval >480 ms. Complete left bundle branch block, second or third degree atrioventricular block. Severe, uncontrolled arrhythmias requiring drug therapy. American New York Heart Association classification ≥ Class III. Cardiac ejection fraction (LVEF) less than 50%. History of myocardial infarction, unstable angina, severe unstable ventricular arrhythmia, or any other arrhythmia requiring treatment, history of clinically severe pericardial disease, or electrocardiographic evidence of acute ischemic or active conduction system abnormalities within 6 months prior to recruitment. Active hepatitis B and C infection (positive hepatitis B virus surface antigen and hepatitis B virus DNA greater than 1 x 103 copies/mL; hepatitis C virus RNA greater than 1 x 103 copies/mL). Human immunodeficiency virus (HIV) infection (HIV antibody positive). previous or current concurrent other malignancies (in addition to effectively controlled non-melanoma basal cell carcinoma of the skin, breast/cervical carcinoma in situ and other malignancies that have not been treated and also effectively controlled within the last five years) Primary or secondary central nervous system (CNS) lymphoma or a history of CNS lymphoma at the time of recruitment. Pregnant and lactating women and patients of childbearing age who do not wish to use contraception Persons with mental disorders/unable to obtain informed consent. Those who are judged by the investigator to be unsuitable for participation in this trial.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    CAG Group

    Arm Description

    Cidapenem combined with azacitidine and mitoxantrone liposomes

    Outcomes

    Primary Outcome Measures

    ORR
    Objective Response Rate

    Secondary Outcome Measures

    2 year PFS rate
    2 year PFS rate
    2 year OS rate
    2 year OS rate
    DOR
    Duration of remission

    Full Information

    First Posted
    December 29, 2022
    Last Updated
    March 6, 2023
    Sponsor
    The First Affiliated Hospital with Nanjing Medical University
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05772728
    Brief Title
    Chidamide Combined With Azacitidine and Mitoxantrone Liposome in the Treatment of Relapsed/Refractory (nTFHL)
    Official Title
    A Multicenter, Single-arm, Open Clinical Efficacy Observational Study of Cidapenem Combined With Azacitidine and Mitoxantrone Liposome (CAM) Regimen for Relapsed/Refractory Intra-nodal Follicular Adjuvant T-cell Lymphoma (nTFHL)
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    March 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    April 2023 (Anticipated)
    Primary Completion Date
    December 2023 (Anticipated)
    Study Completion Date
    December 2024 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    The First Affiliated Hospital with Nanjing Medical University

    4. Oversight

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

    5. Study Description

    Brief Summary
    Intranodal follicular adjuvant T-cell lymphoma (nTFHL) is a type of peripheral T-cell lymphoma (PTCL) that is a new subtype in WHO 2022, which includes 3 categories corresponding to previous angioimmunoblast T-cell lymphoma (AITL), follicular T-cell lymphoma, and PTCL with TFH phenotype, named nTFHL-angioblast type ( nTFHL-AI), nTFHL-follicular (nTFHL-F), and nTFHL-non-specific (nTFH-NOS), respectively.1 nTFHL-AI has a relatively high incidence in PTCL, accounting for about 25-30% of cases, with an aggressive clinical presentation, often with multisystem involvement and with immune system abnormalities. nTFHL shares common immunophenotypic features, namely TFH cell phenotype: CD279/PD1, CD10, BCL6, CXCL13, ICOS, SAP, and CCR5, and at least 2 of the stated immune markers combined with CD4 positivity are required for the diagnosis of nTFHL.1, TFH cell and nTFHL cell also share similar reproducible genetic abnormalities, such as RHOA G17V, DNMT3A, IDH2, TET2, often involving epigenetic genetic abnormalities 2, especially abnormalities of DNMT3A, IDH2, and TET2 are more frequent in myeloid disorders. Basic studies have shown that cidabenamide and anthracyclines have synergistic effects to promote apoptosis in PTCL cells; and the adverse events of the two do not completely overlap, suggesting that a mitoxantrone liposome-based regimen combined with cidabenamide for PTCL may have a better clinical benefit. Based on the above findings, the investigators propose to further investigate the efficacy and safety of cidapenem combined with azacitidine and mitoxantrone liposome (CAM) regimen, i.e., cidapenem combined with azacitidine dual epigenetic modulation on the basis of mitoxantrone liposome, in the treatment of patients with R/R nTFHL using a randomized, prospective, multicenter phase II clinical trial, which is expected to further improve ORR, PFS and OS.
    Detailed Description
    Induction treatment period. Cetapenem 20 mg orally twice a week Azacitidine 75 mg/m2 subcutaneously d1-7 Mitoxantrone liposomes 20 mg/m2 intravenous d6 1 treatment cycle every 21 days. Maintenance treatment period: cidabendiamide 20 mg orally twice weekly/28 days Cycle

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    T Cell Lymphoma

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Not Applicable
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    23 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    CAG Group
    Arm Type
    Experimental
    Arm Description
    Cidapenem combined with azacitidine and mitoxantrone liposomes
    Intervention Type
    Drug
    Intervention Name(s)
    Cidapenem combined with azacitidine and mitoxantrone liposome (CAM) regimen
    Other Intervention Name(s)
    CAM
    Intervention Description
    CAM regimen (every 21 days as a treatment cycle). Cetapenem 20 mg orally twice weekly Azacitidine 75 mg/m2 subcutaneously d1-7 Mitoxantrone liposomes 20 mg/m2 intravenous d6
    Primary Outcome Measure Information:
    Title
    ORR
    Description
    Objective Response Rate
    Time Frame
    6 months
    Secondary Outcome Measure Information:
    Title
    2 year PFS rate
    Description
    2 year PFS rate
    Time Frame
    2 years
    Title
    2 year OS rate
    Description
    2 year OS rate
    Time Frame
    2 years
    Title
    DOR
    Description
    Duration of remission
    Time Frame
    2 years

    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: R/R nTFHL confirmed by pathological tissue, with diagnostic criteria referring to the 2022 WHO diagnostic criteria. Patients who have undergone at least one previous systemic treatment (including chemotherapy, HSCT, etc.) without remission or relapse after remission. Signed written informed consent and who are able to comply with the visits and related procedures specified in the protocol. whole-body PET/CT performed 28 days prior to study entry, which must have at least 1 evaluable or measurable lesion meeting Lugano 2014 criteria: lymph node lesions, measurable lymph nodes need to be >1.5 cm in length; non-lymphoid lesions, measurable extra-nodal lesions need to be >1.0 cm in length. with a PS score of 0 to 2 according to ECOG with adequate organ and bone marrow function, defined as follows: neutrophil count ≥ 1.5×109/L, platelet count ≥ 75×109/L, and hemoglobin ≥ 80 g/L (relaxed to ≥ 1.0×109/L for neutrophil count, ≥ 50×109/L for platelet count, and ≥ 75 g/L for hemoglobin in patients with bone marrow involvement); Liver and kidney function: serum creatinine (Cr) ≤ 1.5 times the upper limit of normal value; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 times the upper limit of normal value (≤ 5 times the upper limit of normal value for patients with liver invasion); total bilirubin (TBIL) ≤ 1.5 times the upper limit of normal value (≤ 3 times the upper limit of normal value for patients with liver invasion); life expectancy of more than 3 months age 18 to 75 years. Exclusion Criteria: Subjects with a history of prior antitumor therapy that is one of the following. Previous recipients of mitoxantrone or mitoxantrone liposomes. Prior treatment with doxorubicin or other anthracyclines with a total cumulative dose of doxorubicin > 360 mg/m2 (other anthracyclines converted to 1 mg doxorubicin equivalent to 2 mg epirubicin). Patients who have received autologous hematopoietic stem cell transplantation (ASCT) within 100 days of the first dose, or who have received allogeneic hematopoietic stem cell transplantation. have received antitumor therapy (including chemotherapy, targeted therapy, hormonal therapy, administration of herbal medicine with antitumor activity, etc.) or participated in other clinical trials and received clinical trial medication within 4 weeks prior to the first administration of this study drug. Hypersensitivity reaction to any investigational drug or its components. Uncontrollable systemic disease (e.g., progressive infection, uncontrollable hypertension, diabetes mellitus, etc.). Cardiac function and disease consistent with one of the following. Long QTc syndrome or QTc interval >480 ms. Complete left bundle branch block, second or third degree atrioventricular block. Severe, uncontrolled arrhythmias requiring drug therapy. American New York Heart Association classification ≥ Class III. Cardiac ejection fraction (LVEF) less than 50%. History of myocardial infarction, unstable angina, severe unstable ventricular arrhythmia, or any other arrhythmia requiring treatment, history of clinically severe pericardial disease, or electrocardiographic evidence of acute ischemic or active conduction system abnormalities within 6 months prior to recruitment. Active hepatitis B and C infection (positive hepatitis B virus surface antigen and hepatitis B virus DNA greater than 1 x 103 copies/mL; hepatitis C virus RNA greater than 1 x 103 copies/mL). Human immunodeficiency virus (HIV) infection (HIV antibody positive). previous or current concurrent other malignancies (in addition to effectively controlled non-melanoma basal cell carcinoma of the skin, breast/cervical carcinoma in situ and other malignancies that have not been treated and also effectively controlled within the last five years) Primary or secondary central nervous system (CNS) lymphoma or a history of CNS lymphoma at the time of recruitment. Pregnant and lactating women and patients of childbearing age who do not wish to use contraception Persons with mental disorders/unable to obtain informed consent. Those who are judged by the investigator to be unsuitable for participation in this trial.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Wei XU, Doctor
    Phone
    025-68306034
    Email
    1151525490@qq.com

    12. IPD Sharing Statement

    Learn more about this trial

    Chidamide Combined With Azacitidine and Mitoxantrone Liposome in the Treatment of Relapsed/Refractory (nTFHL)

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