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A multicenter, open, rnadomized, phase I/II clinical trial toevaluate the safety and efficacy of combined maintenance of rituximab and cytokine-induced killer cells in elderly high-risk DLBCL(Diffuse Large B-cell Lymphoma) patients responding to the first R-CHOP treatment

Status Approved

  • First Submitted Date

    2020/12/02

  • Registered Date

    2020/12/28

  • Last Updated Date

    2020/12/02

CRIS Required

WHO ICTRP (International Clinical Trial Registry Platform) Required

  • 1. Background

    Background - CRIS Registration Number, Unique Protocol ID, Public/Brief Title, Scientific Title, Acronym, MFDS Regulated Study, IND/IDE Protocol, Registered at Other Registry, Name of Registry/Registration Number
    CRIS
    Registration Number
    KCT0005708
    Unique Protocol ID XC20CIDF0042K
    Public/Brief Title A Phase I/II clinical trial to evaluate the safety and efficacy of combined maintenance of rituximab and cytokine-induced killer cells in elderly high-risk lymphoma patients responding to the first chemotherapy
    Scientific Title A multicenter, open, rnadomized, phase I/II clinical trial toevaluate the safety and efficacy of combined maintenance of rituximab and cytokine-induced killer cells in elderly high-risk DLBCL(Diffuse Large B-cell Lymphoma) patients responding to the first R-CHOP treatment
    Acronym RITU_CYTO
    MFDS Regulated Study Yes
    IND/IDE Protocol Yes
    Registered at Other Registry No
    Healthcare Benefit Approval Status Submitted pending
  • 2. Institutional Review Board / Ethics Committee

    Institutional Review Board Information
    Board Approval Status Submitted approval
    Board Approval Number XC20CIDF0042K
    Approval Date 2020-11-24
    Institutional Review Board Name Catholic Central Medical Center Central Clinical Research Review Committee
    Institutional Review Board Address 222, Banpo-daero, Seocho-gu, Seoul
    Institutional Review Board Telephone 02-2258-8203
    Data Monitoring Committee No
  • 3. Contact Details

    Contact Details Information - Contact Person for Principal Investigator / Scientific Queries, Contact Person for Public Queries, Contact Person for Updating Information의 Name, Title, Email, Telephone, Cellular Phone, Affiliation, Address
    Contact Person for Principal Investigator / Scientific Queries
    Name Seok-Goo Cho
    Title Professor
    Telephone +82-2-2258-6052
    Affiliation The Catholic University of Korea, Seoul St. Mary's Hospital
    Address 222 Banpo-daero, Seocho-gu, Seoul
    Contact Person for Public Queries
    Name Nayoun Kim
    Title Production Director
    Telephone +82-2-532-2520
    Affiliation LucasBio
    Address 222 Banpo-daero, Seocho-gu, Seoul
    Contact Person for Updating Information
    Name Nayoun Kim
    Title Production Director
    Telephone +82-2-532-2520
    Affiliation LucasBio
    Address 222 Banpo-daero, Seocho-gu, Seoul
  • 4. Status

    Status Information - Study Site, Overall Recruitment Status, Date of First Enrollment, Status of First Enrollment, Target Number of Participant, Primary Completion Date, Recruitment Status by Participating Study Site, Name of Study Site, Recruitment Status, Date of First Enrollment, Status of First Enrollemnt
    Study Site Multi-center Number of center : 2
    Overall Recruitment Status Not yet recruiting
    Date of First Enrollment 2021-01-01 Anticipated
    Target Number of Participant 36
    Primary Completion Date 2024-01-31 , Anticipated
    Study Completion Date 2025-03-31 , Anticipated
    Recruitment Status by Participating Study Site 1
    Name of Study The Catholic University of Korea, Seoul St. Mary's Hospital
    Recruitment Status Not yet recruiting
    Date of First Enrollment 2021-01-01 ,
    Recruitment Status by Participating Study Site 2
    Name of Study The Catholic University of Korea, Yeouido St. Mary's Hospital
    Recruitment Status Not yet recruiting
    Date of First Enrollment 2021-02-01 ,
  • 5. Source of Monetary / Material Support

    Source of Monetary / Material Support Information - Organization Name, Organization Type, Project ID
    1. Source of Monetary/Material Support
    Organization Name Celltrion Pharm
    Organization Type Pharmaceutical Company
    Project ID
  • 6. Sponsor Organization

    Sponsor Organization Information - Organization Name, Organization Type
    1. Sponsor Organization
    Organization Name The Catholic University of Korea, Seoul St. Mary's Hospital
    Organization Type Medical Institute
  • 7. Study Summary

    Study Summary Information
    Lay Summary
    Objective: To evaluate the safety and efficacy in elderly, high risk DLBCL patients who respond to primary R-CHOP treatment, and receive maintenance therapy with rituximab and cytokine-induced killer cells. Safety is evaluated by observing any adverse reactions and signs that may occur after maintenance therapy. Efficacy is evaluated through 2-year disease-free survival 
    
    Background: Although elderly patients, as in majority of patients, with advanced lymphoma are expected to be treated only by immunochemotherapy, thorough evaluation and caution are needed to determine whether they are suitable for standard therapy or prevent recurrence, The decision is tricky because most elderly patients are unable to receive appropriate treatment regimens and thus lower dose therapies are provided in which leads to a high recurrence rate. Even if all anticancer therapies are completed, intensive supportive care is required which includes antiviral therapy and anti-infective agents to alleviate the toxic effects of chemotherapy. Therefore, elderly patients with advanced lymphoma have high rates of recurrence-related mortality as well as high rates of cancer-related mortality. -	Currently, elderly patients cannot use consolidation therapy such as radiation therapy, autologous stem cell transplantation or additional chemotherapy. Therefore, in the absence of adequate maintenance therapy for elderly patients who have received primary chemotherapy, immune cell therapy which has low toxicity and high anti-tumor effects can be used in combination with targeted antibody therapy to achieve long-term remission
    
    Hypothesis: Immune cell therapy has been continuously developed in pre-clinical and clinical studies. It is known for their high anti-tumor effects and absence of adverse effects, sot it may be feasible and reproducible even in elderly patients. Although targeted antibody therapy can directly bind and kill the tumor cells, the antibody-conjugated tumor cells can also be recognized by killer cells existing in the immune system. Therefore, there is a strong rationale for combining cytokine-induced killer cells with targeted antibodies. 
    
    Clinical research plan:
    The clinical trial will be conducted with subjects who voluntarily consented to participating in the trial. In the subjects who received the first R-CHOP treatment and showed complete response will be further determined whether they are suitable for the selection/exclusion criteria, and then subjects will be randomly assigned to the experimental group and compared with a 1:1 ratio. Randomization and blood collection for the trial group will be completed at least 21 days prior to the first administration.
    Only subjects randomly assigned to the test group will be collected for 250 cc of blood for CIK culture. The collected blood goes through a cell culture process for 3 weeks at the GMP facility of the Cell Therapy Project Group at St. CIK cells (autologous-CIK cells; auto CIK cells) and will be injected intravenously.
  • 8. Study Design

    Study Design Information - Study Type, Study Purpose, Phase, Intervention Model, Blinding/Masking, Blinded Subject, Allocation, Intervention Type, Intervention Description, Number of Arms, Arm Label, Target Number of Participant, Arm Type, Arm Description
    Study Type Interventional Study
    Study Purpose
    Treatment
    Phase Phase1/Phase2
    Intervention Model Parallel  
    Blinding/Masking Open
    Allocation RCT
    Intervention Type Drug, /Biological/Vaccine, /Non-Stem Cell  
    Intervention Description
    Rituximab + autologous CIKcells
    1. Rituximab treatment
      1) Dose: Mix in 500mL of normal saline and inject 375mg/㎡ intravenously
      2) Administration route: intravenous injection
    
    2. Autologous CIK cells (auto CIK cells)
      1) Dose: The number of cells can range from 1x10e9 to 1x10e10 and is provided in a 100mL normal saline bag and is injected intravenously for 30 minutes
      2) Administration route: intravenous injection
    
    Frequency and duration of administration: total of 4 doses every 3 months
    Number of Arms 2
    Arm 1

    Arm Label

    Rituximab+CIK combination therapy

    Target Number of Participant

    18

    Arm Type

    Experimental

    Arm Description

    Rituximab + autologous CIKcells
    1. Rituximab treatment
      1) Dose: Mix in 500mL of normal saline and inject 375mg/㎡ intravenously
      2) Administration route: intravenous injection
    
    2. Autologous CIK cells (auto CIK cells)
      1) Dose: The number of cells can range from 1x10e9 to 1x10e10 and is provided in a 100mL normal saline bag and is injected intravenously for 30 minutes
      2) Administration route: intravenous injection
    
    Frequency and duration of administration: total of 4 doses every 3 months
    Arm 2

    Arm Label

    No treatment

    Target Number of Participant

    18

    Arm Type

    No intervention

    Arm Description

    No treatment(Observational)
  • 9. Subject Eligibility

    Subject Eligibility Information
    Condition(s)/Problem(s)    (D50-D89)Diseases of the blood and blood-forming organs and certain disorders involving the immune mechanism 

    diffuse large B cell lymphoma
    Rare Disease No
    Inclusion Criteria

    Gender

    Both

    Age

    65Year~No Limit

    Description

    1) Patients over 65 years of age
    2) Elderly DLBCL patients with complete response (CR) to the first-line R-CHOP therapy
    3) Patients whose LDH level is higher than the normal range for each laboratory at the time of initial diagnosis
    4) Ann arbor Advanced stage (stage III, IV) or bulky disease
    5) ECOG performance evaluation 0, 1, 2 factors
    6) Patients within 6 months of receiving the first R-CHOP therapy
    7) Those who are judged to be able to survive more than 3 months
    8) Patients who satisfy the following in the blood test
    9) White blood cell count ≥ 3.0 109/L (103/uL)
    10) Platelet count ≥ 750/109/L (103/uL)
    11) Total bilirubin in serum ≤ 2 times the normal upper limit of each laboratory
    12) Serum liver enzyme levels (transaminases, AST, ALT) ≤ 3 times the normal upper limit of each laboratory
    13) Patients who did not receive other immunotherapy
    14) Patients without tuberculosis infection within 6 months
    15) Those who agree to participate in this clinical trial and have consented in writing
    Exclusion Criteria
    1) Pregnant, lactating or pregnant women or women who have not taken adequate contraceptive measures
    2) For men who are sexually active with women of childbearing age, men who do not take appropriate contraception (a double-blocking method that uses a male condom and a cervical cap or under a contraceptive diaphragm and additional spermicide)
    3) Patients with active infection or fever (≥ 38℃) of unknown etiology or ongoing bacterial or fungal infection
    4) HIV, HBV, HCV positive patients
    5) Subjects with cancer history within 5 years
    6) Uncontrolled hypertension (diastolic blood pressure> 115 mmHg)
    7) unstable angina or congestive heart failure (NY class II or higher)
    8) Severe diabetes that is poorly controlled
    9) Those who have undergone coronary angioplasty within the last 6 months
    10) Patients with non-malignant diseases including acute myocardial infarction or uncontrolled atrial or ventricular arrhythmia within the last 6 months
    11) Mental disorder patients, drug addiction
    12) Those who participated in other clinical trials within 30 days before registration
    13) Those who judge that the investigator is unsuitable for participation in the clinical trial
    Healthy Volunteers No
  • 10. Outcome Measure(s)

    Outcome Measure(s) Information - Type of Primary Outcome, Primary Outcome, Outcome, Timepoint, Secondary Outcome, Outcome, Timepoint
    Type of Primary Outcome /Safety/Efficacy
    Primary Outcome(s) 1
    Outcome
    2 year disease free survival
    Timepoint
    At 24 months after treatment
    Primary Outcome(s) 2
    Outcome
    Incidence of adverse reactions of NCI grade 3 or higher
    Timepoint
    0d, 1d, 3M, 6M, 9M, 12M, 15M, 18M, 21M, 24M (on the day and day following injection and every three months for 2 years)
    Secondary Outcome(s) 1
    Outcome
    2 year progression free survival
    Timepoint
    At 24 months after treatment
    Secondary Outcome(s) 2
    Outcome
    Tumor response (complete response or partial response)
    Timepoint
    0D, 3M, 6M, 9M, 12M, 15M, 18M, 21M, 24M (Every 3 months for 2 years)
  • 11. Study Results and Publication

    Study Results and Publication Information - Result Registered, Final Enrollment Number, Number of Publication, Publications, Results Upload, Date of Posting Results, Protocol URL or File Upload, Brief Summary
    Result Registered No
  • 12. Sharing of Study Data(Deidentified Individual-Patient Data, IPD)

    Sharing of Study Data Information - Sharing Statement, Time of Sharing, Way of Sharing
    Sharing Statement No
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