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Linperlisib in Combination With CHOP in Previously Untreated Peripheral T-Cell Lymphoma

Primary Purpose

Peripheral T-cell Lymphoma

Status
Not yet recruiting
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Linperlisib in combination with CHOP
Sponsored by
Sun Yat-sen University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Peripheral T-cell Lymphoma

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Histologically confirmed PTCL, including ALK positive anaplastic large cell lymphoma (ALCL) with an IPI score of ≥ 2, ALK negative ALCL, peripheral T-cell lymphoma non-specific type (PTCL NOS), angioimmunoblastic T-cell lymphoma (AITL), enteropathy related T-cell lymphoma and liver spleen T-cell lymphoma; PTCL patients with CD30 expression<10%, or PTCL patients with CD30 expression ≥ 10% who are unable to receive BV treatment; Has not received anti-tumor treatment in the past; There is at least one measurable lesion: the longest diameter (LDi) of the lymph node lesion is greater than 1.5 cm, or the LDi of one extra lymph node lesion is greater than 1 cm (according to the 2014 Lugano classification); Age range from 18 to 70 years old, regardless of gender; Whole body physical condition score (ECOG) 0-2; Expected survival time>3 months; Adequate bone marrow and organ functions; Not accompanied by hemophagocytic syndrome; If the patient is accompanied by clinically diagnosed hemophagocytic syndrome, after targeted anti hemophagocytic syndrome drug treatment, the researcher evaluates the patient's general physical condition to determine whether they can be enrolled. Volunteer to participate in clinical research and sign an informed consent form, willing to follow and capable of completing all trial procedures. Exclusion Criteria: Received PI3K inhibitor treatment before enrollment; A history of other primary invasive malignant tumors that have not been relieved or have not been relieved for more than 3 years; Involvement of the central nervous system (meninges or brain parenchyma); Individuals who are known to have allergies to any medication in the study Participated in clinical trials of other drugs within 4 weeks prior to the start of the study; Pregnant or lactating women; Individuals with active infections, excluding fever related to tumor B symptoms; Concomitant diseases and medical history: There are many factors affecting oral medicine (such as inability to swallow, chronic diarrhea and Bowel obstruction); Individuals with a history of abuse of psychotropic substances who are unable to quit or have mental disorders; Subjects with any severe and/or uncontrollable diseases, including: Poor blood pressure control (systolic blood pressure ≥ 150mm Hg or diastolic blood pressure ≥ 100 mmHg); Suffering from ≥ Level 2 myocardial ischemia or infarction, arrhythmia (including QTc ≥ 450ms (male), QTc ≥ 470ms (female)), and ≥ Level 2 congestive heart failure (New York Heart Association (NYHA) classification); Active interstitial pneumonia or other chronic lung diseases, leading to severe impairment of lung function, defined as FEV1 and DLCOc<60% of normal predicted values; A history of interstitial pneumonia caused by COVID-19. Liver abnormalities: I. Decompensated cirrhosis (Child Pugh liver function rating of B or C) II Known clinically significant history of liver disease. Including viral hepatitis, known carriers of hepatitis B virus (HBV) must exclude active HBV infection, i.e. HBV DNA positivity (>2500 copies/mL or>500IU/mL, and greater than the upper limit of normal values); Known hepatitis C virus infection (HCV) and HCV RNA positivity (>1 × 103 copies/mL). Note: hepatitis B HBsAg positive subjects who meet the inclusion conditions, whether their HBV DNA is measurable or not, need to continue antiviral treatment (nucleoside analogues are recommended) and regularly monitor HBV DNA; For subjects with positive HBcAb but negative HBsAg in hepatitis B, HBV DNA should be monitored regularly and preventive antiviral treatment should be recommended; Hepatitis C patients need to regularly monitor HCV RNA. Renal failure requiring hemodialysis or Peritoneal dialysis; Subjects with uncontrolled Pleural effusion, pericardial effusion, or ascites requiring repeated drainage; Poor control of diabetes (Fasting blood sugar (FBG)>10mmol/L); Urinary routine examination indicates that urine protein is ≥++, and it is confirmed that 24-hour urine protein quantification is greater than 1.0 g; . Have a history of immune deficiency, including positive Diagnosis of HIV/AIDS, or have other acquired or congenital immune deficiency diseases, or have a history of organ transplantation; . According to the judgment of the researcher, there are serious accompanying diseases that pose a serious threat to the patient's safety or affect the patient's ability to complete the study.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    Linperlisib in combination with CHOP

    Arm Description

    Patients will receive six cycles of induction therapy of linperlisib in combination with CHOP regimen. All patients with CR and PR after induction therapy receive linperlisib maintenance therapy every 28 days until disease progression or other reasons lead to discontinuation, and the duration of linperlisib maintenance does not exceed 24 months.

    Outcomes

    Primary Outcome Measures

    Dose-limiting toxicity (DLT, Phase Ib)
    To identify the DLT
    Complete remission rate (CR rate) based on the 2014 Lugano evaluation criteria (Phase II)
    To investigate the antitumor efficacy

    Secondary Outcome Measures

    Overall response rate (ORR)
    To investigate the antitumor efficacy
    Duration of complete remission
    To investigate the antitumor efficacy
    Duration of remission (DOR)
    To investigate the antitumor efficacy
    Progression free survival (PFS)
    To investigate the antitumor efficacy
    Overall survival (OS)
    To investigate the antitumor efficacy
    Incidence and severity of adverse events (AE) and Serious adverse event (SAE), as well as abnormal laboratory inspection indicators; Quality of Life (QOL).
    To identify the incidence of AE, SAE and QOL.

    Full Information

    First Posted
    July 10, 2023
    Last Updated
    July 10, 2023
    Sponsor
    Sun Yat-sen University
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05949944
    Brief Title
    Linperlisib in Combination With CHOP in Previously Untreated Peripheral T-Cell Lymphoma
    Official Title
    Linperlisib in Combination With CHOP in Previously Untreated Peripheral T-Cell Lymphoma:a Single-Arm, Open Lable, Multicenter Clinical Trial(LINCH Study)
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    July 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    August 2023 (Anticipated)
    Primary Completion Date
    August 2026 (Anticipated)
    Study Completion Date
    December 2026 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    Sun Yat-sen 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
    This phase Ib/II, single arm, open label, multicenter study is conducted to evaluate the efficacy and safety of linperlisib in combination with CHOP for newly diagnosed PTCL patients, and explore the reasonable dosage of linperlisib when combined with CHOP regimen.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Peripheral T-cell Lymphoma

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 1, Phase 2
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    48 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Linperlisib in combination with CHOP
    Arm Type
    Experimental
    Arm Description
    Patients will receive six cycles of induction therapy of linperlisib in combination with CHOP regimen. All patients with CR and PR after induction therapy receive linperlisib maintenance therapy every 28 days until disease progression or other reasons lead to discontinuation, and the duration of linperlisib maintenance does not exceed 24 months.
    Intervention Type
    Drug
    Intervention Name(s)
    Linperlisib in combination with CHOP
    Intervention Description
    Patients will receive six cycles of induction therapy of linperlisib in combination with CHOP regimen. All patients with CR and PR after induction therapy receive linperlisib maintenance therapy every 28 days until disease progression or other reasons lead to discontinuation, and the duration of linperlisib maintenance does not exceed 24 months.
    Primary Outcome Measure Information:
    Title
    Dose-limiting toxicity (DLT, Phase Ib)
    Description
    To identify the DLT
    Time Frame
    The first cycle of linperlisib in combination with R-CHOP regimen (21 days)
    Title
    Complete remission rate (CR rate) based on the 2014 Lugano evaluation criteria (Phase II)
    Description
    To investigate the antitumor efficacy
    Time Frame
    Up to 18 weeks
    Secondary Outcome Measure Information:
    Title
    Overall response rate (ORR)
    Description
    To investigate the antitumor efficacy
    Time Frame
    Up to 18 weeks
    Title
    Duration of complete remission
    Description
    To investigate the antitumor efficacy
    Time Frame
    From date of complete remission to the study treatment until the date of the first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
    Title
    Duration of remission (DOR)
    Description
    To investigate the antitumor efficacy
    Time Frame
    From date of remission to the study treatment until the date of the first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
    Title
    Progression free survival (PFS)
    Description
    To investigate the antitumor efficacy
    Time Frame
    From date of the first injection until the date of the first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
    Title
    Overall survival (OS)
    Description
    To investigate the antitumor efficacy
    Time Frame
    From date of the first injection until the date of death from ant cause, assessed up to 24 months
    Title
    Incidence and severity of adverse events (AE) and Serious adverse event (SAE), as well as abnormal laboratory inspection indicators; Quality of Life (QOL).
    Description
    To identify the incidence of AE, SAE and QOL.
    Time Frame
    Through study completion, an average of 2 years

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    70 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Histologically confirmed PTCL, including ALK positive anaplastic large cell lymphoma (ALCL) with an IPI score of ≥ 2, ALK negative ALCL, peripheral T-cell lymphoma non-specific type (PTCL NOS), angioimmunoblastic T-cell lymphoma (AITL), enteropathy related T-cell lymphoma and liver spleen T-cell lymphoma; PTCL patients with CD30 expression<10%, or PTCL patients with CD30 expression ≥ 10% who are unable to receive BV treatment; Has not received anti-tumor treatment in the past; There is at least one measurable lesion: the longest diameter (LDi) of the lymph node lesion is greater than 1.5 cm, or the LDi of one extra lymph node lesion is greater than 1 cm (according to the 2014 Lugano classification); Age range from 18 to 70 years old, regardless of gender; Whole body physical condition score (ECOG) 0-2; Expected survival time>3 months; Adequate bone marrow and organ functions; Not accompanied by hemophagocytic syndrome; If the patient is accompanied by clinically diagnosed hemophagocytic syndrome, after targeted anti hemophagocytic syndrome drug treatment, the researcher evaluates the patient's general physical condition to determine whether they can be enrolled. Volunteer to participate in clinical research and sign an informed consent form, willing to follow and capable of completing all trial procedures. Exclusion Criteria: Received PI3K inhibitor treatment before enrollment; A history of other primary invasive malignant tumors that have not been relieved or have not been relieved for more than 3 years; Involvement of the central nervous system (meninges or brain parenchyma); Individuals who are known to have allergies to any medication in the study Participated in clinical trials of other drugs within 4 weeks prior to the start of the study; Pregnant or lactating women; Individuals with active infections, excluding fever related to tumor B symptoms; Concomitant diseases and medical history: There are many factors affecting oral medicine (such as inability to swallow, chronic diarrhea and Bowel obstruction); Individuals with a history of abuse of psychotropic substances who are unable to quit or have mental disorders; Subjects with any severe and/or uncontrollable diseases, including: Poor blood pressure control (systolic blood pressure ≥ 150mm Hg or diastolic blood pressure ≥ 100 mmHg); Suffering from ≥ Level 2 myocardial ischemia or infarction, arrhythmia (including QTc ≥ 450ms (male), QTc ≥ 470ms (female)), and ≥ Level 2 congestive heart failure (New York Heart Association (NYHA) classification); Active interstitial pneumonia or other chronic lung diseases, leading to severe impairment of lung function, defined as FEV1 and DLCOc<60% of normal predicted values; A history of interstitial pneumonia caused by COVID-19. Liver abnormalities: I. Decompensated cirrhosis (Child Pugh liver function rating of B or C) II Known clinically significant history of liver disease. Including viral hepatitis, known carriers of hepatitis B virus (HBV) must exclude active HBV infection, i.e. HBV DNA positivity (>2500 copies/mL or>500IU/mL, and greater than the upper limit of normal values); Known hepatitis C virus infection (HCV) and HCV RNA positivity (>1 × 103 copies/mL). Note: hepatitis B HBsAg positive subjects who meet the inclusion conditions, whether their HBV DNA is measurable or not, need to continue antiviral treatment (nucleoside analogues are recommended) and regularly monitor HBV DNA; For subjects with positive HBcAb but negative HBsAg in hepatitis B, HBV DNA should be monitored regularly and preventive antiviral treatment should be recommended; Hepatitis C patients need to regularly monitor HCV RNA. Renal failure requiring hemodialysis or Peritoneal dialysis; Subjects with uncontrolled Pleural effusion, pericardial effusion, or ascites requiring repeated drainage; Poor control of diabetes (Fasting blood sugar (FBG)>10mmol/L); Urinary routine examination indicates that urine protein is ≥++, and it is confirmed that 24-hour urine protein quantification is greater than 1.0 g; . Have a history of immune deficiency, including positive Diagnosis of HIV/AIDS, or have other acquired or congenital immune deficiency diseases, or have a history of organ transplantation; . According to the judgment of the researcher, there are serious accompanying diseases that pose a serious threat to the patient's safety or affect the patient's ability to complete the study.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Qingqing Cai, MD. PhD.
    Phone
    0086-20-87342823
    Email
    caiqq@sysucc.org.cn

    12. IPD Sharing Statement

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    Linperlisib in Combination With CHOP in Previously Untreated Peripheral T-Cell Lymphoma

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