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出境医 / 临床实验 / Anti-CD30 CAR-T Therapy in Patients With Refractory/Relapsed Lymphocyte Malignancies

Anti-CD30 CAR-T Therapy in Patients With Refractory/Relapsed Lymphocyte Malignancies

Study Description
Brief Summary:
The overall purpose of this study is to explore the safety and therapeutic effect of CD30-targeted chimeric antigen receptor T(CAR-T) cells in the treatment of Refractory/Relapsed lymphocyte malignancies.

Condition or disease Intervention/treatment Phase
Adult T-Cell Lymphoma/Leukaemia Anaplastic Large Cell Lymphoma Angioimmunoblastic T-cell Lymphoma NK/T-cell Lymphoma Peripheral T Cell Lymphoma Hodgkin Lymphoma Genetic: Anti-CD30 CAR T cells Phase 1

Detailed Description:
Chimeric antigen receptor (CAR)-modified T cells (CAR-T cells) have the capabilities to recognize tumor associated antigen and kill tumor cells specifically. CD30 is originally described as a marker of Hodgkin's and R-S cells in Hodgkin's lymphoma. CD30 antibody has been applied to treat lymphocyte derived malignancies. To explore the potency of CD30 in CAR-T therapy, this trial is designed and conducted to test the safety and efficacy of CD30-targeted CAR-T in Refractory/Relapsed lymphocyte malignancies.
Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: Single-center,Open,One-arm Clinical Study
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Efficacy and Safety of Anti-CD30 CAR-T Therapy in Patients With Refractory/Relapsed Lymphocyte Malignancies：a Single-center, Open, Single-arm Clinical Study.
Actual Study Start Date : July 3, 2019
Estimated Primary Completion Date : July 1, 2022
Estimated Study Completion Date : January 1, 2023
Arms and Interventions
Arm Intervention/treatment
Experimental: Anti-CD30 CAR T cells
Patients receive CD30 CAR-T cells transduced with a lentiviral vector on day 0 in the absence of disease progression or unacceptable toxicity. Autologous 3th generation anti-CD30 CAR T cells.
 Genetic: Anti-CD30 CAR T cells
Patients receive CD30 CAR-T cells transduced with a lentiviral vector on day 0 in the absence of disease progression or unacceptable toxicity. Autologous 3th generation anti-CD30 CAR T cells.
Outcome Measures
Primary Outcome Measures :
  1. Number of participants with adverse events [ Time Frame: 3 years ]
    Therapy-related adverse events were recorded and assessed according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, Version 4.0).


Secondary Outcome Measures :
  1. One-month remission rate [ Time Frame: 1 month ]
    Response to CAR-T therapy was assessed on day 30 (±2), against the National Comprehensive Cancer Network (NCCN, Version 1.2015).

  2. Overall survival [ Time Frame: 3 years ]
    OS was calculated from the first CAR-T cell infusion to death or last follow-up (censored).

  3. Event-free survival [ Time Frame: 3 years ]
    EFS was calculated from the first CAR-T cell infusion to death, progression of the disease, relapse or gene recurrence, whichever came first, or last visit (censored).

  4. Relapse-free survival [ Time Frame: 3 years ]
    RFS was calculated from the first CAR-T cell infusion to relapse or last visit (censored).

  5. Quantity of anti-CD30 CAR-T cells in bone marrow cells and peripheral blood cells [ Time Frame: 3 years ]
    In vivo (bone marrow and peripheral blood) quantity of CAR-T cells were determined by means of flow cytometry.

  6. Quantity of anti-CD30 CAR copies in bone marrow cells and peripheral blood cells [ Time Frame: 3 years ]
    In vivo (bone marrow and peripheral blood) quantity of anti-CD30 CAR copies were determined by means of qPCR.


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patient or his or her legal guardian voluntarily participates in and signs an informed consent form.
  2. Male or female patients aged 18 to 70 years (including 18 and 70 years old).
  3. Pathological and histological examination confirmed CD30+ lymphocyte malignancies, and patients currently have no effective treatment options, such as chemotherapy or recurrence after hematopoietic stem cell transplantation; or patients voluntarily choose Anti-CD30 CAR-T as rescue treatment.

  4. CD30+ lymphocyte malignancies:

    1. Adult T-cell leukemia/lymphoma
    2. Anaplastic large cell lymphoma (ALCL);
    3. Angioimmunoblastic T-cell Lymphoma (AITL);
    4. NK/T-cell lymphoma;
    5. Peripheral T-cell lymphoma (PTCL);
    6. Hodgkin lymphoma;

  5. Subjects:

    1. There are still residual lesions after major treatment, and they are not suitable for HSCT (auto/allo-HSCT);
    2. Recurrence occurs after CR1, and HSCT (auto/allo-HSCT) is not selected or suitable because of self-willingness;
    3. After hematopoietic stem cell transplantation or cellular immunotherapy, the patient suffered relapse or did not remission.
  6. Having a measurable or evaluable lesion.

  7. Patient's main organs function well：

    1. Liver function: ALT/AST < 3 times the upper limit of normal (ULN) and
    2. total bilirubin≤34.2μmol/L
    3. Renal function: Creatinine < 220μmol/L.
    4. Pulmonary function: Indoor oxygen saturation≥95%.
    5. Cardiac Function: Left ventricular ejection fraction (LVEF) ≥40%.
  8. The patients did not receive any anticancer treatments such as chemotherapy, radiotherapy and immunotherapy (such as immunosuppressive drugs) within 4 weeks before admission, and the toxicity related to previous treatments had returned to < 1 level at admission (except for low toxicity such as alopecia).
  9. The patient's peripheral superficial venous blood flow smoothly, which can meet the needs of intravenous drip.
  10. Patient ECOG score≤2, Estimated survival time≥3 months.

Exclusion Criteria:

  1. Women who are pregnant (urine/blood pregnancy test positive) or lactating.
  2. Male or female with a conception plan in the past 1 years.
  3. Patients cannot guarantee effective contraception (condom or contraceptives, etc.) within 1 years after enrollment.
  4. Uncontrolled infectious disease within 4 weeks prior to enrollment.
  5. Active hepatitis B/C virus.
  6. HIV infected patients.
  7. Suffering from a serious autoimmune disease or immunodeficiency disease.
  8. The patient is allergic and is allergic to macromolecular biopharmaceuticals such as antibodies or cytokines.
  9. The patient participated in other clinical trials within 6 weeks prior to enrollment.
  10. Systemic use of hormones within 4 weeks prior to enrollment (except for patients with inhaled corticosteroids).
  11. Have a history of epilepsy or other central nervous system diseases.
  12. Having drug abuse/addiction.
  13. According to the researcher's judgment, the patient has other unsuitable grouping conditions.
Contacts and Locations

Contacts
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Contact: Yu Hu, M.D. Ph.D 86-13986183871 dr_huyu@126.com
Contact: Heng Mei, M.D. Ph.D 86-13886160811 hmei@hust.edu.cn

Locations
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China, Hubei
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology Recruiting
Wuhan, Hubei, China, 430022
Contact: Yu Hu, M.D., Ph.D    86-13986183871    dr_huyu@126.com   
Contact: Heng Mei, M.D., Ph.D    86-13886160811    hmei@hust.edu.cn   
Sponsors and Collaborators
Wuhan Union Hospital, China
Wuhan Bio-Raid Biotechnology Co, Ltd. China
Investigators
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Principal Investigator: Heng Mei, M.D. Ph.D Wuhan Union Hospital, China
Tracking Information
First Submitted Date  ICMJE July 2, 2019
First Posted Date  ICMJE July 5, 2019
Last Update Posted Date August 7, 2019
Actual Study Start Date  ICMJE July 3, 2019
Estimated Primary Completion Date July 1, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 2, 2019) 		Number of participants with adverse events [ Time Frame: 3 years ]
Therapy-related adverse events were recorded and assessed according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, Version 4.0).
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 2, 2019)
  • One-month remission rate [ Time Frame: 1 month ]
    Response to CAR-T therapy was assessed on day 30 (±2), against the National Comprehensive Cancer Network (NCCN, Version 1.2015).
  • Overall survival [ Time Frame: 3 years ]
    OS was calculated from the first CAR-T cell infusion to death or last follow-up (censored).
  • Event-free survival [ Time Frame: 3 years ]
    EFS was calculated from the first CAR-T cell infusion to death, progression of the disease, relapse or gene recurrence, whichever came first, or last visit (censored).
  • Relapse-free survival [ Time Frame: 3 years ]
    RFS was calculated from the first CAR-T cell infusion to relapse or last visit (censored).
  • Quantity of anti-CD30 CAR-T cells in bone marrow cells and peripheral blood cells [ Time Frame: 3 years ]
    In vivo (bone marrow and peripheral blood) quantity of CAR-T cells were determined by means of flow cytometry.
  • Quantity of anti-CD30 CAR copies in bone marrow cells and peripheral blood cells [ Time Frame: 3 years ]
    In vivo (bone marrow and peripheral blood) quantity of anti-CD30 CAR copies were determined by means of qPCR.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Anti-CD30 CAR-T Therapy in Patients With Refractory/Relapsed Lymphocyte Malignancies
Official Title  ICMJE Efficacy and Safety of Anti-CD30 CAR-T Therapy in Patients With Refractory/Relapsed Lymphocyte Malignancies：a Single-center, Open, Single-arm Clinical Study.
Brief Summary The overall purpose of this study is to explore the safety and therapeutic effect of CD30-targeted chimeric antigen receptor T(CAR-T) cells in the treatment of Refractory/Relapsed lymphocyte malignancies.
Detailed Description Chimeric antigen receptor (CAR)-modified T cells (CAR-T cells) have the capabilities to recognize tumor associated antigen and kill tumor cells specifically. CD30 is originally described as a marker of Hodgkin's and R-S cells in Hodgkin's lymphoma. CD30 antibody has been applied to treat lymphocyte derived malignancies. To explore the potency of CD30 in CAR-T therapy, this trial is designed and conducted to test the safety and efficacy of CD30-targeted CAR-T in Refractory/Relapsed lymphocyte malignancies.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:
Single-center,Open,One-arm Clinical Study
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Adult T-Cell Lymphoma/Leukaemia
  • Anaplastic Large Cell Lymphoma
  • Angioimmunoblastic T-cell Lymphoma
  • NK/T-cell Lymphoma
  • Peripheral T Cell Lymphoma
  • Hodgkin Lymphoma
Intervention  ICMJE Genetic: Anti-CD30 CAR T cells
Patients receive CD30 CAR-T cells transduced with a lentiviral vector on day 0 in the absence of disease progression or unacceptable toxicity. Autologous 3th generation anti-CD30 CAR T cells.
Study Arms  ICMJE Experimental: Anti-CD30 CAR T cells
Patients receive CD30 CAR-T cells transduced with a lentiviral vector on day 0 in the absence of disease progression or unacceptable toxicity. Autologous 3th generation anti-CD30 CAR T cells.
Intervention: Genetic: Anti-CD30 CAR T cells
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 2, 2019) 		50
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 1, 2023
Estimated Primary Completion Date July 1, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Patient or his or her legal guardian voluntarily participates in and signs an informed consent form.
  2. Male or female patients aged 18 to 70 years (including 18 and 70 years old).
  3. Pathological and histological examination confirmed CD30+ lymphocyte malignancies, and patients currently have no effective treatment options, such as chemotherapy or recurrence after hematopoietic stem cell transplantation; or patients voluntarily choose Anti-CD30 CAR-T as rescue treatment.

  4. CD30+ lymphocyte malignancies:

    1. Adult T-cell leukemia/lymphoma
    2. Anaplastic large cell lymphoma (ALCL);
    3. Angioimmunoblastic T-cell Lymphoma (AITL);
    4. NK/T-cell lymphoma;
    5. Peripheral T-cell lymphoma (PTCL);
    6. Hodgkin lymphoma;

  5. Subjects:

    1. There are still residual lesions after major treatment, and they are not suitable for HSCT (auto/allo-HSCT);
    2. Recurrence occurs after CR1, and HSCT (auto/allo-HSCT) is not selected or suitable because of self-willingness;
    3. After hematopoietic stem cell transplantation or cellular immunotherapy, the patient suffered relapse or did not remission.
  6. Having a measurable or evaluable lesion.

  7. Patient's main organs function well：

    1. Liver function: ALT/AST < 3 times the upper limit of normal (ULN) and
    2. total bilirubin≤34.2μmol/L
    3. Renal function: Creatinine < 220μmol/L.
    4. Pulmonary function: Indoor oxygen saturation≥95%.
    5. Cardiac Function: Left ventricular ejection fraction (LVEF) ≥40%.
  8. The patients did not receive any anticancer treatments such as chemotherapy, radiotherapy and immunotherapy (such as immunosuppressive drugs) within 4 weeks before admission, and the toxicity related to previous treatments had returned to < 1 level at admission (except for low toxicity such as alopecia).
  9. The patient's peripheral superficial venous blood flow smoothly, which can meet the needs of intravenous drip.
  10. Patient ECOG score≤2, Estimated survival time≥3 months.

Exclusion Criteria:

  1. Women who are pregnant (urine/blood pregnancy test positive) or lactating.
  2. Male or female with a conception plan in the past 1 years.
  3. Patients cannot guarantee effective contraception (condom or contraceptives, etc.) within 1 years after enrollment.
  4. Uncontrolled infectious disease within 4 weeks prior to enrollment.
  5. Active hepatitis B/C virus.
  6. HIV infected patients.
  7. Suffering from a serious autoimmune disease or immunodeficiency disease.
  8. The patient is allergic and is allergic to macromolecular biopharmaceuticals such as antibodies or cytokines.
  9. The patient participated in other clinical trials within 6 weeks prior to enrollment.
  10. Systemic use of hormones within 4 weeks prior to enrollment (except for patients with inhaled corticosteroids).
  11. Have a history of epilepsy or other central nervous system diseases.
  12. Having drug abuse/addiction.
  13. According to the researcher's judgment, the patient has other unsuitable grouping conditions.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Yu Hu, M.D. Ph.D 86-13986183871 dr_huyu@126.com
Contact: Heng Mei, M.D. Ph.D 86-13886160811 hmei@hust.edu.cn
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04008394
Other Study ID Numbers  ICMJE WHUH-CART-CD30-01
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party MEI HENG, Wuhan Union Hospital, China
Study Sponsor  ICMJE Wuhan Union Hospital, China
Collaborators  ICMJE Wuhan Bio-Raid Biotechnology Co, Ltd. China
Investigators  ICMJE
Principal Investigator: Heng Mei, M.D. Ph.D Wuhan Union Hospital, China
PRS Account Wuhan Union Hospital, China
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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