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出境医 / 临床实验 / γδT Cells Immunotherapy in Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma (NHL)

γδT Cells Immunotherapy in Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma (NHL)

Study Description
Brief Summary:
This study aims to evaluate the safety and efficacy of autologous γδT cells in patients with relapsed or refractory B cell non-Hodgkin's lymphoma (B-NHL), chronic lymphoblastic leukemia (CLL) and peripheral T cell lymphoma (PTCL) expect for γδT lymphoma.

Condition or disease Intervention/treatment Phase
Non-Hodgkin's Lymphoma Relapsed or Refractory B Cell Non-Hodgkin's Lymphoma Chronic Lymphoblastic Leukemia Peripheral T Cell Lymphoma Biological: Autologous γδT cells Early Phase 1

Detailed Description:
This is a single-centre, non-randomised, open label, no control, prospective clinical trial. The study will include the following sequential phases: sign informed consent, γδT cells pre-culture, screening and registration to the trial, apheresis, γδT cells preparation, pre-treatment for lymphodepleting chemotherapy (selectable plan), treatment and follow-up. The study will evaluate the safety and efficacy of the autologous γδT cells in patients with relapsed or refractory B cell non-Hodgkin's lymphoma (B-NHL), chronic lymphoblastic leukemia (CLL) and peripheral T cell lymphoma (PTCL) expect for γδT lymphoma.
Study Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 6 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: Biological: Autologous γδT cells Cells will be extracted by apheresis, followed by expanding and activating. The autologous γδT cells product will be adoptive transferred.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Preliminary Exploration of γδT Cells Immunotherapy in Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma (NHL).
Estimated Study Start Date : October 2019
Estimated Primary Completion Date : December 31, 2020
Estimated Study Completion Date : March 31, 2022
Arms and Interventions
Arm Intervention/treatment
Experimental: Autologous γδT cells
Subjects will receive 3 cycles of γδT cells treatments, at four-week intervals, each cycle has 2 infusions, single infusion intravenously at a target dose of 1~2×10e9 γδT cells (constant dose).
 Biological: Autologous γδT cells
Cells will be extracted by apheresis, followed by expanding and activating. The autologous γδT cells product will be adoptive transferred.
Outcome Measures
Primary Outcome Measures :
  1. Number of Participants with Severe/Adverse Events as a Measure of Safety. [ Time Frame: 15 months ]
    Incidence of adverse events (AEs) and serious adverse events (SAEs) of each patient will be recorded and analyzed.

  2. Overall response rate (ORR) [ Time Frame: 28 days after infusion of γδT cells ]
    Rate of complete remission (CR) and partial remission (PR).


Secondary Outcome Measures :
  1. Duration of remission (DOR) [ Time Frame: 15 months ]
    Duration of remission is defined as the time from the first occurrence of CR or PR in the tumor assessment to the first occurrence of disease progression (PD) or death.

  2. Time to response(TTR) [ Time Frame: 15 months ]
    Time to response is defined as the time from the first administration of trial drug to the first occurrence of CR or PR in the tumor assessment.

  3. Disease control rate (DCR) [ Time Frame: 15 months ]
    Disease control rate is defined as the proportion of subjects who achieved CR, PR, and disease stability (SD) by imaging evaluation.

  4. Progression free survival (PFS) [ Time Frame: 15 months ]
    Progression free survival is defined as the time from the day in which the patient is enrolled to the date on which tumor progresses or the date on which the patient dies for any cause.

  5. Overall survival (OS) [ Time Frame: 15 months ]
    Overall survival is defined as the time from the day in which the patient is enrolled to the date on which the patient dies for any cause.


Eligibility Criteria
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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. Patients should sign informed consent form voluntarily.
  2. Gender unlimited, age ≥ 18 years old.
  3. Patients with relapsed or refractory B cell non-Hodgkin's lymphoma (B-NHL), chronic lymphoblastic leukemia (CLL) and peripheral T cell lymphoma(PTCL) expect for γδT lymphoma.
  4. Patients had an evaluable imaging lesion of at least greater than 1.5 cm (except CLL).
  5. Eastern Cooperative Oncology Group (ECOG) Performance status 0-2.
  6. Adequate bone marrow function as defined by：Absolute neutrophil count (ANC) >1000/mm3；Absolute lymphocyte count (ALC) ≥300/mm3；Platelet ≥50000/mm3；Hemoglobin >8.0g/dl.
  7. Adequate end organ function as defined by: Total bilirubin ≤ 2 x upper limit of normal（ULN）; Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 5 x ULN; Creatinine ≤ 1.5 x ULN or any serum creatinine level associated with a measured or calculated creatinine clearance of ≥ 60ml/min.
  8. Male and female of reproductive potential must agree to use birth control during the study and for at least 6 weeks post study.

Exclusion Criteria:

  1. Patients with history of allogeneic hematopoietic stem cell transplantation (Allo-HSCT).
  2. Active central nervous system (CNS) lymphoma; Patients with symptoms of CNS disease must undergo lumbar puncture and brain nuclear magnetic resonance to exclude CNS lymphoma.

  3. Patients receiving chemotherapy within 2 weeks prior to γδT cell infusion, with the following exceptions:

    • Pretreatment chemotherapy prescribed by the protocol
    • In order to prevent CNS intrathecal chemotherapy (should be stopped 1 week before γδT cell therapy)
    • Other exploratory combined medications
  4. Patients with systemic vasculitis, or with active or uncontrolled autoimmune diseases, as well as primary or secondary immunodeficiency diseases.
  5. Active chronic hepatitis B or hepatitis C virus infection, active cytomegalovirus (CMV), EBV infection.
  6. Major surgery that was evaluated by the investigator as unsuitable for inclusion within 4 weeks prior to screening.

  7. History of other malignant tumors, with the following exceptions

    • Excisional non-melanoma (e.g. cutaneous basal cell carcinoma)
    • Cured situ carcinoma (e.g. cervical carcinoma)
    • Localized prostate cancer with radiotherapy or surgery
    • Patients with a history of malignant tumors, but the disease has been cured for ≥2 years

  8. Patient's cardiac function meets any of the following conditions

    • Left ventricular ejection fraction (LVEF) ≤45%
    • Class III or IV heart failure according to the NYHA Heart Failure Classifications
    • QTcB>450 msec
    • Other cardiac disease that investigators judge is not suitable for enrollment
  9. History of epilepsy or other active central nervous system disorders.
  10. Inoculated live vaccine within 6 weeks before screening.
  11. Uncontrolled serious active infection (such as sepsis, bacteremia and fungemia).
  12. Patients are allergic to cytokines.
  13. Expected survival < 12 weeks.
  14. Participated in any other interventional clinical trial within three months.
  15. Any situation that investigators believe the risk of the subjects is increased or results of the trial are disturbed.
Contacts and Locations

Contacts
Layout table for location contacts
Contact: Dehui Zou, Dr. 86-022-23909283 zoudehui@ihcams.ac.cn
Contact: Shuhua Yi, Dr. 86-022-23909106 yishuhua@ihcams.ac.cn

Locations
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China, Tianjin
Institute of Hematology & Blood Diseases Hospital Recruiting
Tianjin, Tianjin, China, 300020
Contact: Dehui Zou, Dr.    86-022-23909283    zoudehui@ihcams.ac.cn   
Contact: Shuhua Yi, Dr.    86-022-23909106    yishuhua@ihcams.ac.cn   
Sponsors and Collaborators
Institute of Hematology & Blood Diseases Hospital
Beijing GD Initiative Cell Therapy Technology Co., Ltd.
Chinese Academy of Medical Sciences
Investigators
Layout table for investigator information
Principal Investigator: Dehui Zou, Dr. Institute of Hematology & Blood Disease Hospital
Tracking Information
First Submitted Date  ICMJE July 18, 2019
First Posted Date  ICMJE July 22, 2019
Last Update Posted Date September 26, 2019
Estimated Study Start Date  ICMJE October 2019
Estimated Primary Completion Date December 31, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 19, 2019)
  • Number of Participants with Severe/Adverse Events as a Measure of Safety. [ Time Frame: 15 months ]
    Incidence of adverse events (AEs) and serious adverse events (SAEs) of each patient will be recorded and analyzed.
  • Overall response rate (ORR) [ Time Frame: 28 days after infusion of γδT cells ]
    Rate of complete remission (CR) and partial remission (PR).
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 19, 2019)
  • Duration of remission (DOR) [ Time Frame: 15 months ]
    Duration of remission is defined as the time from the first occurrence of CR or PR in the tumor assessment to the first occurrence of disease progression (PD) or death.
  • Time to response(TTR) [ Time Frame: 15 months ]
    Time to response is defined as the time from the first administration of trial drug to the first occurrence of CR or PR in the tumor assessment.
  • Disease control rate (DCR) [ Time Frame: 15 months ]
    Disease control rate is defined as the proportion of subjects who achieved CR, PR, and disease stability (SD) by imaging evaluation.
  • Progression free survival (PFS) [ Time Frame: 15 months ]
    Progression free survival is defined as the time from the day in which the patient is enrolled to the date on which tumor progresses or the date on which the patient dies for any cause.
  • Overall survival (OS) [ Time Frame: 15 months ]
    Overall survival is defined as the time from the day in which the patient is enrolled to the date on which the patient dies for any cause.
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 γδT Cells Immunotherapy in Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma (NHL)
Official Title  ICMJE Preliminary Exploration of γδT Cells Immunotherapy in Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma (NHL).
Brief Summary This study aims to evaluate the safety and efficacy of autologous γδT cells in patients with relapsed or refractory B cell non-Hodgkin's lymphoma (B-NHL), chronic lymphoblastic leukemia (CLL) and peripheral T cell lymphoma (PTCL) expect for γδT lymphoma.
Detailed Description This is a single-centre, non-randomised, open label, no control, prospective clinical trial. The study will include the following sequential phases: sign informed consent, γδT cells pre-culture, screening and registration to the trial, apheresis, γδT cells preparation, pre-treatment for lymphodepleting chemotherapy (selectable plan), treatment and follow-up. The study will evaluate the safety and efficacy of the autologous γδT cells in patients with relapsed or refractory B cell non-Hodgkin's lymphoma (B-NHL), chronic lymphoblastic leukemia (CLL) and peripheral T cell lymphoma (PTCL) expect for γδT lymphoma.
Study Type  ICMJE Interventional
Study Phase  ICMJE Early Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:
Biological: Autologous γδT cells Cells will be extracted by apheresis, followed by expanding and activating. The autologous γδT cells product will be adoptive transferred.
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Non-Hodgkin's Lymphoma
  • Relapsed or Refractory B Cell Non-Hodgkin's Lymphoma
  • Chronic Lymphoblastic Leukemia
  • Peripheral T Cell Lymphoma
Intervention  ICMJE Biological: Autologous γδT cells
Cells will be extracted by apheresis, followed by expanding and activating. The autologous γδT cells product will be adoptive transferred.
Study Arms  ICMJE Experimental: Autologous γδT cells
Subjects will receive 3 cycles of γδT cells treatments, at four-week intervals, each cycle has 2 infusions, single infusion intravenously at a target dose of 1~2×10e9 γδT cells (constant dose).
Intervention: Biological: Autologous γδT 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 19, 2019) 		6
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 31, 2022
Estimated Primary Completion Date December 31, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Patients should sign informed consent form voluntarily.
  2. Gender unlimited, age ≥ 18 years old.
  3. Patients with relapsed or refractory B cell non-Hodgkin's lymphoma (B-NHL), chronic lymphoblastic leukemia (CLL) and peripheral T cell lymphoma(PTCL) expect for γδT lymphoma.
  4. Patients had an evaluable imaging lesion of at least greater than 1.5 cm (except CLL).
  5. Eastern Cooperative Oncology Group (ECOG) Performance status 0-2.
  6. Adequate bone marrow function as defined by：Absolute neutrophil count (ANC) >1000/mm3；Absolute lymphocyte count (ALC) ≥300/mm3；Platelet ≥50000/mm3；Hemoglobin >8.0g/dl.
  7. Adequate end organ function as defined by: Total bilirubin ≤ 2 x upper limit of normal（ULN）; Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 5 x ULN; Creatinine ≤ 1.5 x ULN or any serum creatinine level associated with a measured or calculated creatinine clearance of ≥ 60ml/min.
  8. Male and female of reproductive potential must agree to use birth control during the study and for at least 6 weeks post study.

Exclusion Criteria:

  1. Patients with history of allogeneic hematopoietic stem cell transplantation (Allo-HSCT).
  2. Active central nervous system (CNS) lymphoma; Patients with symptoms of CNS disease must undergo lumbar puncture and brain nuclear magnetic resonance to exclude CNS lymphoma.

  3. Patients receiving chemotherapy within 2 weeks prior to γδT cell infusion, with the following exceptions:

    • Pretreatment chemotherapy prescribed by the protocol
    • In order to prevent CNS intrathecal chemotherapy (should be stopped 1 week before γδT cell therapy)
    • Other exploratory combined medications
  4. Patients with systemic vasculitis, or with active or uncontrolled autoimmune diseases, as well as primary or secondary immunodeficiency diseases.
  5. Active chronic hepatitis B or hepatitis C virus infection, active cytomegalovirus (CMV), EBV infection.
  6. Major surgery that was evaluated by the investigator as unsuitable for inclusion within 4 weeks prior to screening.

  7. History of other malignant tumors, with the following exceptions

    • Excisional non-melanoma (e.g. cutaneous basal cell carcinoma)
    • Cured situ carcinoma (e.g. cervical carcinoma)
    • Localized prostate cancer with radiotherapy or surgery
    • Patients with a history of malignant tumors, but the disease has been cured for ≥2 years

  8. Patient's cardiac function meets any of the following conditions

    • Left ventricular ejection fraction (LVEF) ≤45%
    • Class III or IV heart failure according to the NYHA Heart Failure Classifications
    • QTcB>450 msec
    • Other cardiac disease that investigators judge is not suitable for enrollment
  9. History of epilepsy or other active central nervous system disorders.
  10. Inoculated live vaccine within 6 weeks before screening.
  11. Uncontrolled serious active infection (such as sepsis, bacteremia and fungemia).
  12. Patients are allergic to cytokines.
  13. Expected survival < 12 weeks.
  14. Participated in any other interventional clinical trial within three months.
  15. Any situation that investigators believe the risk of the subjects is increased or results of the trial are disturbed.
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: Dehui Zou, Dr. 86-022-23909283 zoudehui@ihcams.ac.cn
Contact: Shuhua Yi, Dr. 86-022-23909106 yishuhua@ihcams.ac.cn
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04028440
Other Study ID Numbers  ICMJE QT2019001-EC-2
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 Zou Dehui, Institute of Hematology & Blood Diseases Hospital
Study Sponsor  ICMJE Institute of Hematology & Blood Diseases Hospital
Collaborators  ICMJE
  • Beijing GD Initiative Cell Therapy Technology Co., Ltd.
  • Chinese Academy of Medical Sciences
Investigators  ICMJE
Principal Investigator: Dehui Zou, Dr. Institute of Hematology & Blood Disease Hospital
PRS Account Institute of Hematology & Blood Diseases Hospital
Verification Date July 2019

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

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