search
Back to results

Anti-PD-1 Antibody Combined With Autologous DC and NK Cells in the Treatment of Digestive Carcinoma

Primary Purpose

PD-1 Antibody, DC-Cell, NK-Cell

Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Pembrolizumab
Nivolumab
Sintilimab
Toripalimab
Camrelizumab
Tislelizumab
NK-Cell or DC-Cell
Sponsored by
China Medical University, China
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for PD-1 Antibody

Eligibility Criteria

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

Inclusion Criteria:

-1. age: 18-70 years, of either sex 2. pathologically confirmed locally advanced or metastatic gastrointestinal tumour (stage III or IV according to AJCC 8th edition staging) with at least one measurable lesion (meeting RECIST 1.1 criteria) 3. ECOG PS: 0-1 points 4. have adequate organ and bone marrow function, i.e. meet the following criteria.

  1. Routine blood test criteria to be met.

    1. HB ≥ 90g/L.
    2. ANC ≥1.5×109/L.
    3. PLT ≥90 x 109/L.
    4. Absolute value of lymphocytes + monocytes >2.0*10^9/L.
  2. Biochemical tests are required to meet the following criteria.

    1. Total bilirubin ≤ 1.5 times the upper limit of normal (ULN).
    2. ALT and AST ≤ 2.5ULN.
    3. serum Cr ≤ 1 ULN and endogenous creatinine clearance > 60 ml/min (Cockcroft-Gault formula).

      5. international normalised ratio (INR) ≤ 1.5 and partial thromboplastin time (PPT or APTT) ≤ 1.5 ULN within 7 days prior to enrolment 6. expected survival of ≥ 3 months. 7. signed informed consent form (ICF) prior to study enrolment. 8 Women of childbearing potential must have had a pregnancy test (serum or urine) within 7 days prior to enrolment and have a negative result. Female patients of childbearing age or male patients whose sexual partners are women of childbearing age are required to use effective contraception throughout the treatment period and for 6 months after the last dose.

      Exclusion Criteria:

      • 1. known hypersensitivity to any of the components of the anti-PD-1 antibody formulation; or previous severe allergic reactions to other monoclonal antibodies.

        2. diagnosis of other malignancies, excluding radically treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin and/or radically resected carcinoma in situ, within 5 years prior to the first dose 3. Subjects who have been treated with an antitumour vaccine or other antitumour agents with immunostimulatory effects (interferon, interleukin, thymidine, immune cell therapy, etc.) within 1 month prior to the first dose.

        4. CNS metastases with symptoms. Subjects may be enrolled in the study if their CNS metastases have been treated, e.g., clinical stability (MRI detection) has been maintained for at least 4 weeks, and the subject's clinical symptoms, such as neurological symptoms, are able to return to baseline levels at least 2 weeks prior to the first dose (except for residual signs or symptoms related to CNS treatment). In addition, subjects receiving stable or tapered doses of ≤10 mg/day of prednisone (or equivalent) for at least 2 weeks for clinical symptoms associated with treatment with corticosteroids are not eligible for enrollment in the study, otherwise they cannot be enrolled.

        5. Acute or chronic active hepatitis B (defined as positive HBsAg for hepatitis B virus surface antigen at screening) or hepatitis C infection. Patients with previous hepatitis B virus (HBV) infection or cured HBV infection (defined as hepatitis B core (HBc) antibody positive and HBsAg negative) who are negative for HBV DNA only may be enrolled in this study. HBV DNA testing must be performed on this group of patients prior to enrolment. Patients who are positive for hepatitis C virus (HCV) antibodies and negative for HCV RNA only by polymerase chain reaction may be enrolled in the study. Patients who are antigen-positive but have DNA/RNA copy numbers within the permissible range should be considered for antiviral treatment if enrolled in this study and DNA/RNA levels should be monitored in real time for the duration of the study.

        6. previous and current history of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, drug-related pneumonia, severely impaired lung function and other lung diseases.

        7. active tuberculosis (TB), on anti-TB treatment or who have received anti-TB treatment within 1 year prior to the first dose 8. Human immunodeficiency virus (HIV) infected (HIV-positive), known syphilis infection 9. Patients who are considered to be at high medical risk due to severe, uncontrollable disease, non-metastatic systemic disease or having an active, uncontrollable infection. Some examples include, but not all, uncontrolled ventricular arrhythmias, recent (within 3 months) myocardial infarction, uncontrollable grand mal seizures, unstable spinal cord compression, superior vena cava syndrome, HRCT suggestive of extensive bilateral interstitial lung disease or any mental illness that may prevent informed consent from being obtained 10. active autoimmune disease requiring systemic therapy (e.g. use of disease-relieving drugs, corticosteroids or immunosuppressants) that occurred within 2 years prior to the first dose Alternative therapies (e.g. thyroxine, insulin or physiological corticosteroids for adrenal or pituitary insufficiency, etc.) are permitted Known history of primary immunodeficiency. Patients with positive autoimmune antibodies only need to confirm the presence of autoimmune disease at the discretion of the investigator.

        11. Use of immunosuppressive drugs within 4 weeks prior to first dose, excluding topical glucocorticoids by nasal spray, inhalation or other routes or physiological doses of systemic glucocorticoids (i.e. not more than 10 mg/day prednisone or equivalent doses of other glucocorticoids), temporary use of glucocorticoids for the treatment of symptoms of dyspnea in conditions such as asthma, chronic obstructive pulmonary disease is permitted.

        12. exclude subjects who have undergone major surgical procedures within 4 weeks prior to first dose, non-thoracic radiation therapy >30 Gy within 4 weeks prior to first dose, chest radiation >30 Gy within 24 weeks prior to first dose, and palliative radiation <30 Gy within 2 weeks prior to first dose who have not recovered from the toxicity and/or complications of these interventions to NCI-CTC AE ≤1 degree (except alopecia and fatigue excluded) in subjects. Palliative radiotherapy for symptom control is permitted and must be completed at least 2 weeks prior to the start of treatment with the study drug and no additional radiotherapy is planned for the same lesion. For patients who have received radiotherapy prior to 2 weeks prior to the first dose, all of the following conditions must be met for enrolment: absence of any current radiotherapy-related toxic effects, no need for glucocorticoids, exclusion of radiation pneumonia, radiation hepatitis, radiation enteritis, etc.

        13. Pregnant or breastfeeding women. 14. Participated in a clinical trial of another drug within four weeks. 15. Not considered suitable for inclusion by the investigator. Exclude subjects with a history or current evidence of any disease, treatment or laboratory abnormality that may confound the results of the study, interfere with the subject's participation in the study procedures or is not in the best interest of the subject's participation in the study.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    Anti-PD-1 antibody combined with autologous DC and NK cells

    Arm Description

    Anti-PD-1 antibodies (one of six options) Pembrolizumab: 2 mg/kg or 200 mg by intravenous infusion every 3 weeks Nivolumab:3 mg/kg or 240 mg by intravenous infusion every 2 weeks Sintilimab: 200 mg by intravenous infusion every 3 weeks Toripalimab: 3 mg/kg or 240 mg by intravenous infusion every 2 weeks Camrelizumab: 200 mg by intravenous infusion every 2 or 3 weeks, or 3 mg/kg by intravenous infusion every 3 weeks Tislelilzumab: 200mg by intravenous infusion every 3 weeks. DC, NK cells. 50ml of peripheral blood is collected 1 day before the dosing cycle for in vitro isolation and expansion of DC and NK cells; the first infusion of DC and NK cells (not less than 1x10^6 cells/Kg) is completed on day 14.

    Outcomes

    Primary Outcome Measures

    Progression-free Survival (PFS)
    PFS, defined as the time from randomization to the first occurrence of disease progression as determined by the investigator with use of RECIST v1.1 or death from any cause, whichever occurs first.

    Secondary Outcome Measures

    Objective Response Rate (ORR)
    ORR, determined using RECIST v1.1, defined as best overall response (CR or PR) across all assessment time points during the period from enrolment to termination of trial treatment.
    Disease Control Rate (DCR)
    Determined using RECIST v1.1 criteria.
    Overall Survival (OS)
    Duration from the date of initial treatment to the date of death due to any cause.

    Full Information

    First Posted
    July 14, 2022
    Last Updated
    July 14, 2022
    Sponsor
    China Medical University, China
    search

    1. Study Identification

    Unique Protocol Identification Number
    NCT05461235
    Brief Title
    Anti-PD-1 Antibody Combined With Autologous DC and NK Cells in the Treatment of Digestive Carcinoma
    Official Title
    A Prospective, Open, Single-arm Phase II Clinical Study to Evaluate the Efficacy and Safety of Anti-PD-1 Antibody Combined With Autologous DC and NK Cells in the Treatment of Digestive Carcinoma.
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    July 2022
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    July 15, 2022 (Anticipated)
    Primary Completion Date
    July 15, 2025 (Anticipated)
    Study Completion Date
    December 1, 2025 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    China Medical University, China

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    This is a prospective, open, single-arm Phase II clinical study to evaluate the efficacy and safety of anti-PD-1 antibody combined with autologous DC and NK cells in the treatment of digestive carcinoma.
    Detailed Description
    This is a prospective, open, single-arm Phase II clinical study to evaluate the efficacy and safety of anti-PD-1 antibody combined with autologous DC and NK cells in the treatment of digestive carcinoma. This project aims to enhance the anti-tumour activity of DC/NK cells in combination with anti-PD-1 antibodies, and ultimately activate the patient's own immune function to improve the quality of life and survival time of tumour patients, and provide objective evidence for the widespread use of targeted immune cell therapy in the clinical setting.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    PD-1 Antibody, DC-Cell, NK-Cell, Gastrointestinal Tumours

    7. Study Design

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

    8. Arms, Groups, and Interventions

    Arm Title
    Anti-PD-1 antibody combined with autologous DC and NK cells
    Arm Type
    Experimental
    Arm Description
    Anti-PD-1 antibodies (one of six options) Pembrolizumab: 2 mg/kg or 200 mg by intravenous infusion every 3 weeks Nivolumab:3 mg/kg or 240 mg by intravenous infusion every 2 weeks Sintilimab: 200 mg by intravenous infusion every 3 weeks Toripalimab: 3 mg/kg or 240 mg by intravenous infusion every 2 weeks Camrelizumab: 200 mg by intravenous infusion every 2 or 3 weeks, or 3 mg/kg by intravenous infusion every 3 weeks Tislelilzumab: 200mg by intravenous infusion every 3 weeks. DC, NK cells. 50ml of peripheral blood is collected 1 day before the dosing cycle for in vitro isolation and expansion of DC and NK cells; the first infusion of DC and NK cells (not less than 1x10^6 cells/Kg) is completed on day 14.
    Intervention Type
    Drug
    Intervention Name(s)
    Pembrolizumab
    Other Intervention Name(s)
    Keytruda
    Intervention Description
    2mg/kg or 200mg,iv,q3w
    Intervention Type
    Drug
    Intervention Name(s)
    Nivolumab
    Other Intervention Name(s)
    Opdivo
    Intervention Description
    3mg/kg or 240mg,iv,q2w
    Intervention Type
    Drug
    Intervention Name(s)
    Sintilimab
    Other Intervention Name(s)
    Daboshu
    Intervention Description
    200mg,iv,q3w
    Intervention Type
    Drug
    Intervention Name(s)
    Toripalimab
    Other Intervention Name(s)
    Tuoyi
    Intervention Description
    3mg/kg or 240mg,iv,q2w
    Intervention Type
    Drug
    Intervention Name(s)
    Camrelizumab
    Other Intervention Name(s)
    Airuika
    Intervention Description
    200mg,iv,q2w or q3w;3mg/kg,iv,q3w
    Intervention Type
    Drug
    Intervention Name(s)
    Tislelizumab
    Other Intervention Name(s)
    Baizean
    Intervention Description
    200mg,iv,q3w
    Intervention Type
    Biological
    Intervention Name(s)
    NK-Cell or DC-Cell
    Intervention Description
    50ml of peripheral blood was collected 1 day before the dosing cycle for in vitro isolation and amplification of DC and NK cells; the first transfusion of DC and NK cells (not less than 1x10^6 cells/Kg) was completed on day 14.
    Primary Outcome Measure Information:
    Title
    Progression-free Survival (PFS)
    Description
    PFS, defined as the time from randomization to the first occurrence of disease progression as determined by the investigator with use of RECIST v1.1 or death from any cause, whichever occurs first.
    Time Frame
    one year
    Secondary Outcome Measure Information:
    Title
    Objective Response Rate (ORR)
    Description
    ORR, determined using RECIST v1.1, defined as best overall response (CR or PR) across all assessment time points during the period from enrolment to termination of trial treatment.
    Time Frame
    one year
    Title
    Disease Control Rate (DCR)
    Description
    Determined using RECIST v1.1 criteria.
    Time Frame
    one year
    Title
    Overall Survival (OS)
    Description
    Duration from the date of initial treatment to the date of death due to any cause.
    Time Frame
    two 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: -1. age: 18-70 years, of either sex 2. pathologically confirmed locally advanced or metastatic gastrointestinal tumour (stage III or IV according to AJCC 8th edition staging) with at least one measurable lesion (meeting RECIST 1.1 criteria) 3. ECOG PS: 0-1 points 4. have adequate organ and bone marrow function, i.e. meet the following criteria. Routine blood test criteria to be met. HB ≥ 90g/L. ANC ≥1.5×109/L. PLT ≥90 x 109/L. Absolute value of lymphocytes + monocytes >2.0*10^9/L. Biochemical tests are required to meet the following criteria. Total bilirubin ≤ 1.5 times the upper limit of normal (ULN). ALT and AST ≤ 2.5ULN. serum Cr ≤ 1 ULN and endogenous creatinine clearance > 60 ml/min (Cockcroft-Gault formula). 5. international normalised ratio (INR) ≤ 1.5 and partial thromboplastin time (PPT or APTT) ≤ 1.5 ULN within 7 days prior to enrolment 6. expected survival of ≥ 3 months. 7. signed informed consent form (ICF) prior to study enrolment. 8 Women of childbearing potential must have had a pregnancy test (serum or urine) within 7 days prior to enrolment and have a negative result. Female patients of childbearing age or male patients whose sexual partners are women of childbearing age are required to use effective contraception throughout the treatment period and for 6 months after the last dose. Exclusion Criteria: 1. known hypersensitivity to any of the components of the anti-PD-1 antibody formulation; or previous severe allergic reactions to other monoclonal antibodies. 2. diagnosis of other malignancies, excluding radically treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin and/or radically resected carcinoma in situ, within 5 years prior to the first dose 3. Subjects who have been treated with an antitumour vaccine or other antitumour agents with immunostimulatory effects (interferon, interleukin, thymidine, immune cell therapy, etc.) within 1 month prior to the first dose. 4. CNS metastases with symptoms. Subjects may be enrolled in the study if their CNS metastases have been treated, e.g., clinical stability (MRI detection) has been maintained for at least 4 weeks, and the subject's clinical symptoms, such as neurological symptoms, are able to return to baseline levels at least 2 weeks prior to the first dose (except for residual signs or symptoms related to CNS treatment). In addition, subjects receiving stable or tapered doses of ≤10 mg/day of prednisone (or equivalent) for at least 2 weeks for clinical symptoms associated with treatment with corticosteroids are not eligible for enrollment in the study, otherwise they cannot be enrolled. 5. Acute or chronic active hepatitis B (defined as positive HBsAg for hepatitis B virus surface antigen at screening) or hepatitis C infection. Patients with previous hepatitis B virus (HBV) infection or cured HBV infection (defined as hepatitis B core (HBc) antibody positive and HBsAg negative) who are negative for HBV DNA only may be enrolled in this study. HBV DNA testing must be performed on this group of patients prior to enrolment. Patients who are positive for hepatitis C virus (HCV) antibodies and negative for HCV RNA only by polymerase chain reaction may be enrolled in the study. Patients who are antigen-positive but have DNA/RNA copy numbers within the permissible range should be considered for antiviral treatment if enrolled in this study and DNA/RNA levels should be monitored in real time for the duration of the study. 6. previous and current history of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, drug-related pneumonia, severely impaired lung function and other lung diseases. 7. active tuberculosis (TB), on anti-TB treatment or who have received anti-TB treatment within 1 year prior to the first dose 8. Human immunodeficiency virus (HIV) infected (HIV-positive), known syphilis infection 9. Patients who are considered to be at high medical risk due to severe, uncontrollable disease, non-metastatic systemic disease or having an active, uncontrollable infection. Some examples include, but not all, uncontrolled ventricular arrhythmias, recent (within 3 months) myocardial infarction, uncontrollable grand mal seizures, unstable spinal cord compression, superior vena cava syndrome, HRCT suggestive of extensive bilateral interstitial lung disease or any mental illness that may prevent informed consent from being obtained 10. active autoimmune disease requiring systemic therapy (e.g. use of disease-relieving drugs, corticosteroids or immunosuppressants) that occurred within 2 years prior to the first dose Alternative therapies (e.g. thyroxine, insulin or physiological corticosteroids for adrenal or pituitary insufficiency, etc.) are permitted Known history of primary immunodeficiency. Patients with positive autoimmune antibodies only need to confirm the presence of autoimmune disease at the discretion of the investigator. 11. Use of immunosuppressive drugs within 4 weeks prior to first dose, excluding topical glucocorticoids by nasal spray, inhalation or other routes or physiological doses of systemic glucocorticoids (i.e. not more than 10 mg/day prednisone or equivalent doses of other glucocorticoids), temporary use of glucocorticoids for the treatment of symptoms of dyspnea in conditions such as asthma, chronic obstructive pulmonary disease is permitted. 12. exclude subjects who have undergone major surgical procedures within 4 weeks prior to first dose, non-thoracic radiation therapy >30 Gy within 4 weeks prior to first dose, chest radiation >30 Gy within 24 weeks prior to first dose, and palliative radiation <30 Gy within 2 weeks prior to first dose who have not recovered from the toxicity and/or complications of these interventions to NCI-CTC AE ≤1 degree (except alopecia and fatigue excluded) in subjects. Palliative radiotherapy for symptom control is permitted and must be completed at least 2 weeks prior to the start of treatment with the study drug and no additional radiotherapy is planned for the same lesion. For patients who have received radiotherapy prior to 2 weeks prior to the first dose, all of the following conditions must be met for enrolment: absence of any current radiotherapy-related toxic effects, no need for glucocorticoids, exclusion of radiation pneumonia, radiation hepatitis, radiation enteritis, etc. 13. Pregnant or breastfeeding women. 14. Participated in a clinical trial of another drug within four weeks. 15. Not considered suitable for inclusion by the investigator. Exclude subjects with a history or current evidence of any disease, treatment or laboratory abnormality that may confound the results of the study, interfere with the subject's participation in the study procedures or is not in the best interest of the subject's participation in the study.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Yunpeng Liu, PhD
    Phone
    86-24-83282312
    Email
    cmu_trial@163.com
    First Name & Middle Initial & Last Name or Official Title & Degree
    Ling Xu, PhD
    Email
    cmuxuling@163.com
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Yunpeng Liu, PhD
    Organizational Affiliation
    First Hospital of China Medical University
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    No

    Learn more about this trial

    Anti-PD-1 Antibody Combined With Autologous DC and NK Cells in the Treatment of Digestive Carcinoma

    We'll reach out to this number within 24 hrs