4006-776-356 出国就医服务电话

免费获得国外相关药品,最快 1 个工作日回馈药物信息

出境医 / 临床实验 / Ex-vivo Expanded γδ T Lymphocytes in Patients With Refractory/Relapsed Acute Myeloid Leukaemia

Ex-vivo Expanded γδ T Lymphocytes in Patients With Refractory/Relapsed Acute Myeloid Leukaemia

Study Description
Brief Summary:
This study investigates the potential curative properties of ex-vivo expanded gamma delta T-cells obtained from a blood-related donor for patients with relapsed or refractory acute myeloid leukemia.

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia Biological: Ex-vivo Expanded γδ T Lymphocytes Phase 1

Detailed Description:
This is a single-center, open-label, single-arm study to evaluate the safety and efficacy of ex-vivo expanded γδ T-lymphocytes in patients with relapsed or refractory acute myeloid leukemia. PBMCs will be separated from peripheral blood of suitable donors. After making them potential cancer killer γδ T Cells, they will be infused to the patients as an immunotherapy treatment.
Study Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 38 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Efficacy and Safety of Ex-vivo Expanded γδ T Lymphocytes in Patients With Refractory/Relapsed Acute Myeloid Leukaemia: a Single-center, Open-label, Single-arm Clinical Study.
Estimated Study Start Date : September 1, 2019
Estimated Primary Completion Date : July 1, 2022
Estimated Study Completion Date : January 1, 2023
Arms and Interventions
Arm Intervention/treatment
Experimental: Ex-vivo Expanded γδ T Lymphocytes
Patients receive ex-vivo expanded γδ T Lymphocytes (Dose escalation, 2*10^6, 4*10^6, 8*10^6 of cells per kg of body weight).
Biological: Ex-vivo Expanded γδ T Lymphocytes
Patients receive ex-vivo expanded γδ T Lymphocytes (Dose escalation, 2*10^6, 4*10^6, 8*10^6 of cells per kg of body weight).

Outcome Measures
Primary Outcome Measures :
  1. Four-months remission rate [ Time Frame: 4 months ]
    Number of patients reaching Complete Remission (CR) according to National Comprehensive Cancer Network (NCCN, Version 1.2015).

  2. Number of participants with adverse events (AEs) [ 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. Overall survival [ Time Frame: 3 years ]
    OS was calculated from the first infusion to death or last follow-up (censored).

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

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

  4. Quantity of gamma-delta T cells in bone marrow cells and peripheral blood cells [ Time Frame: 3 years ]
    Persistence of γδ T cells assessed by number and phenotype of γδ T cells using flow cytometry assay in peripheral blood and bone marrow from patients

  5. lymphocyte subsets function assessment of bone marrow cells and peripheral blood cells [ Time Frame: 3 years ]
    Assessment of lymphocyte subsets function using flow cytometry assay in peripheral blood and bone marrow from patients.


Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. History of acute myeloid leukaemia (initially diagnosed by presence of 20% or more blast cells with myeloid or monocytic differentiation confirmed by flow cytometry in peripheral blood or bone marrow)
  2. Relapsed or refractory AML. A. AML relapse after intensive chemotherapy; B. AML relapse after allogeneic HCT; C. AML progression on low intensity therapy (low dose cytarabine, 5-azacytidine or decitabine); D. No response to at least 4 cycles of low intensity therapy; E. AML refractory to 2 cycles of induction chemotherapy.
  3. Presence of > 5% of blasts in bone marrow or peripheral blood smear
  4. Patient not eligible for or does not consent to high dose salvage chemotherapy and/or allogeneic Haematopoietic Cell Transplantation (HCT)
  5. Considered suitable for lymphodepleting chemotherapy
  6. The patient's peripheral superficial venous blood flow smoothly, which can meet the needs of intravenous drip.
  7. Patient's main organs function well. A. Liver function: ALT/AST < 3 times the upper limit of normal (ULN); B. total bilirubin≤34.2μmol/L; C. Renal function: Creatinine < 220μmol/L; D. Pulmonary function: Indoor oxygen saturation≥95%; E. Cardiac Function: Left ventricular ejection fraction (LVEF) ≥40%;
  8. Life expectancy of at least 3 months
  9. Patient ECOG score≤2, Estimated survival time≥3 months.
  10. Ability to be off systemic prednisone and other immunosuppressive drugs for at least 3 days prior to γδ T cells product infusion. Maintenance replacement steroid is allowed.
  11. 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).
  12. Patient able to understand and sign written informed consent
  13. Age 18 years up to the age of 75 (≤ 75)

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
Layout table for location contacts
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
Layout table for location information
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
Jinan University, China
Investigators
Layout table for investigator information
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
Estimated Study Start Date  ICMJE September 1, 2019
Estimated Primary Completion Date July 1, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 3, 2019)
  • Four-months remission rate [ Time Frame: 4 months ]
    Number of patients reaching Complete Remission (CR) according to National Comprehensive Cancer Network (NCCN, Version 1.2015).
  • Number of participants with adverse events (AEs) [ 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
 (submitted: July 2, 2019)
  • Four-months remission rate [ Time Frame: 4 months ]
    Evaluation of remission rate according to National Comprehensive Cancer Network (NCCN, Version 1.2015).
  • Number of participants with adverse events (AEs) [ 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).
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 3, 2019)
  • Overall survival [ Time Frame: 3 years ]
    OS was calculated from the first infusion to death or last follow-up (censored).
  • Event-free survival [ Time Frame: 3 years ]
    EFS was calculated from the first 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 infusion to relapse or last visit (censored).
  • Quantity of gamma-delta T cells in bone marrow cells and peripheral blood cells [ Time Frame: 3 years ]
    Persistence of γδ T cells assessed by number and phenotype of γδ T cells using flow cytometry assay in peripheral blood and bone marrow from patients
  • lymphocyte subsets function assessment of bone marrow cells and peripheral blood cells [ Time Frame: 3 years ]
    Assessment of lymphocyte subsets function using flow cytometry assay in peripheral blood and bone marrow from patients.
Original Secondary Outcome Measures  ICMJE
 (submitted: July 2, 2019)
  • Overall survival [ Time Frame: 3 years ]
    OS was calculated from the first infusion to death or last follow-up (censored).
  • Event-free survival [ Time Frame: 3 years ]
    EFS was calculated from the first 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 infusion to relapse or last visit (censored).
  • Quantity of gamma-delta T cells in bone marrow cells and peripheral blood cells [ Time Frame: 3 years ]
    Persistence of γδ T cells assessed by number and phenotype of γδ T cells using flow cytometry assay in peripheral blood and bone marrow from patients
  • lymphocyte subsets function assessment of bone marrow cells and peripheral blood cells [ Time Frame: 3 years ]
    Using flow cytometry assay in peripheral blood and bone marrow from patients.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Ex-vivo Expanded γδ T Lymphocytes in Patients With Refractory/Relapsed Acute Myeloid Leukaemia
Official Title  ICMJE Efficacy and Safety of Ex-vivo Expanded γδ T Lymphocytes in Patients With Refractory/Relapsed Acute Myeloid Leukaemia: a Single-center, Open-label, Single-arm Clinical Study.
Brief Summary This study investigates the potential curative properties of ex-vivo expanded gamma delta T-cells obtained from a blood-related donor for patients with relapsed or refractory acute myeloid leukemia.
Detailed Description This is a single-center, open-label, single-arm study to evaluate the safety and efficacy of ex-vivo expanded γδ T-lymphocytes in patients with relapsed or refractory acute myeloid leukemia. PBMCs will be separated from peripheral blood of suitable donors. After making them potential cancer killer γδ T Cells, they will be infused to the patients as an immunotherapy treatment.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Acute Myeloid Leukemia
Intervention  ICMJE Biological: Ex-vivo Expanded γδ T Lymphocytes
Patients receive ex-vivo expanded γδ T Lymphocytes (Dose escalation, 2*10^6, 4*10^6, 8*10^6 of cells per kg of body weight).
Study Arms  ICMJE Experimental: Ex-vivo Expanded γδ T Lymphocytes
Patients receive ex-vivo expanded γδ T Lymphocytes (Dose escalation, 2*10^6, 4*10^6, 8*10^6 of cells per kg of body weight).
Intervention: Biological: Ex-vivo Expanded γδ T Lymphocytes
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)
38
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. History of acute myeloid leukaemia (initially diagnosed by presence of 20% or more blast cells with myeloid or monocytic differentiation confirmed by flow cytometry in peripheral blood or bone marrow)
  2. Relapsed or refractory AML. A. AML relapse after intensive chemotherapy; B. AML relapse after allogeneic HCT; C. AML progression on low intensity therapy (low dose cytarabine, 5-azacytidine or decitabine); D. No response to at least 4 cycles of low intensity therapy; E. AML refractory to 2 cycles of induction chemotherapy.
  3. Presence of > 5% of blasts in bone marrow or peripheral blood smear
  4. Patient not eligible for or does not consent to high dose salvage chemotherapy and/or allogeneic Haematopoietic Cell Transplantation (HCT)
  5. Considered suitable for lymphodepleting chemotherapy
  6. The patient's peripheral superficial venous blood flow smoothly, which can meet the needs of intravenous drip.
  7. Patient's main organs function well. A. Liver function: ALT/AST < 3 times the upper limit of normal (ULN); B. total bilirubin≤34.2μmol/L; C. Renal function: Creatinine < 220μmol/L; D. Pulmonary function: Indoor oxygen saturation≥95%; E. Cardiac Function: Left ventricular ejection fraction (LVEF) ≥40%;
  8. Life expectancy of at least 3 months
  9. Patient ECOG score≤2, Estimated survival time≥3 months.
  10. Ability to be off systemic prednisone and other immunosuppressive drugs for at least 3 days prior to γδ T cells product infusion. Maintenance replacement steroid is allowed.
  11. 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).
  12. Patient able to understand and sign written informed consent
  13. Age 18 years up to the age of 75 (≤ 75)

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 75 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 NCT04008381
Other Study ID Numbers  ICMJE WHUH-2009-V010
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
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 Jinan University, 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

治疗医院