Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Memory-enriched CAR-T Cells Immunotherapy for B Cell Lymphoma (MeCAR)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02652910
Recruitment Status : Recruiting
First Posted : January 12, 2016
Last Update Posted : February 27, 2019
Sponsor:
Collaborators:
Xuzhou Medical University
Hrain Biotechnology Co., Ltd.
Shanghai Changzheng Hospital
Information provided by (Responsible Party):
Qingzhu Jia, M.D., Xinqiao Hospital of Chongqing

Tracking Information
First Submitted Date  ICMJE November 18, 2015
First Posted Date  ICMJE January 12, 2016
Last Update Posted Date February 27, 2019
Study Start Date  ICMJE December 2015
Estimated Primary Completion Date June 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 11, 2016)
  • Phase 1: Safety measured by occurrence of study related adverse effects defined by NCI CTCAE 4.0 [ Time Frame: 4 weeks ]
  • Phase 2: Overall complete remission rate defined by the standard response criteria for malignant lymphoma for each arm [ Time Frame: 8 weeks ]
  • Phase 2: Comparison of overall complete remission rate for the two arms [ Time Frame: One year ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02652910 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 11, 2016)
  • Duration of remission [ Time Frame: One year ]
  • Minimum residual disease negative remission rate [ Time Frame: 8 weeks ]
  • Duration of CAR-positive T cells in circulation [ Time Frame: 6 months ]
  • Total number of CAR-positive T cells infiltrated into lymphoma tissue [ Time Frame: 6 months ]
  • Overall survival [ Time Frame: One year ]
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 Memory-enriched CAR-T Cells Immunotherapy for B Cell Lymphoma
Official Title  ICMJE A Two-Arm, Single-Center, Open-Label Pilot Study of IL-2 Programmed or IL-7/IL-15 Programmed Anti-CD19:TCRz:CD28 T-cells in Patient With CD19-Positive Lymphoma That is Resistant or Refractory to Chemotherapy
Brief Summary The goal of this clinical trial is to study how approaches for manufacturing chimeric antigen receptor (CAR)-modified T (CAR-T) cells affect their in vivo persistence and therapeutic efficacy against B lymphoma. Recently, cancer immunotherapy, treatments aiming to arm patients with immunity specifically against cancer cells, has emerged as a promising therapeutic strategy. Among the many emerging immunotherapeutic approaches, clinical trials utilizing CARs against B cell malignancies have demonstrated remarkable potential. CARs combine the variable region of an antibody with T-cell signaling moieties to confer T-cell activation with the targeting specificity of an antibody. Thus, CARs are not MHC-restricted so they are not vulnerable to MHC down regulation by tumors. However, defined by the activation and contraction program of their mother cells, the persistency and function of CAR-T cells are also restricted by the protocol of manufacturing. Previous clinical studies largely utilized interleukin-2 (IL-2) for the ex vivo expansion of CAR-T cells, which preferentially generate CAR-T cells with characteristics of terminally differentiated effector cells. Our preliminary data indicated that two common gamma chain cytokines, IL-7 and IL-15, can help to selectively expand CAR-T cells with various memory phenotypes. CAR-T Cells prepared under this condition resulted in improved therapeutic efficacy in preclinical animal models. This clinical investigation is to test a hypothesis whether IL-7/IL-15-programmed anti-CD19 CAR-T cells persist longer in lymphoma patients after infusion and whether the persistency of CAR-T cells can lead to improved anti-lymphoma efficacy.
Detailed Description

Primary Objectives

  1. To determine the safety and feasibility of CD19.CAR-T cells manufactured through IL-7/IL-15-mediated expansion or IL-2-mediated expansion
  2. To determine in vivo dynamics and persistency of IL-7/IL-15 programmed CD19.CAR-T cells.
  3. To determine the efficacy of IL-7/IL-15 programmed CD19.CAR-T cells in treating patients with CD19-positive lymphoma

Secondary Objectives

  1. To determine whether the IL-7/IL-15 programmed CD19.CAR-T cells are superior to the IL-2 programmed cells as measured by their in vivo persistence post infusion
  2. To determine whether the IL-7/IL-15 programmed CD19.CAR-T cells are superior to the IL-2 programmed cells as measured by their efficacy in lymphoma therapy
  3. To assess the dynamics of intratumoral infiltration of CD19.CAR-T cells.
  4. To correlate the subsets and differentiation of CD19.CAR-T cells to observed anti-tumor efficacy
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Recurrent Adult Diffuse Large Cell Lymphoma
  • Recurrent Follicular Lymphoma
  • Recurrent Mantle Cell Lymphoma
  • Stage III Adult Diffuse Large Cell Lymphoma
  • Stage III Follicular Lymphoma
  • Stage III Mantle Cell Lymphoma
  • Stage IV Adult Diffuse Large Cell Lymphoma
  • Stage IV Follicular Lymphoma
  • Stage IV Mantle Cell Lymphoma
Intervention  ICMJE Drug: CD19.CAR-T cells
Retroviral vector-transduced autologous T cells to express CD19-specific CARs
Other Name: DSCAR01
Study Arms  ICMJE
  • Experimental: IL-2 programmed CD19.CAR-T cells
    Administrated with IL-2 programmed CD19.CAR-T cells on day 0,1,2 in the lympho-depleted patients
    Intervention: Drug: CD19.CAR-T cells
  • Experimental: IL-7/IL-15 programmed CD19.CAR-T cells
    Administrated with IL-7/IL-15 programmed CD19.CAR-T cells on day 0,1,2 in the lympho-depleted patients
    Intervention: Drug: CD19.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: January 11, 2016)
20
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2019
Estimated Primary Completion Date June 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. 18 Years to 70 Years, Male and female;
  2. Expected survival > 12 weeks;
  3. Performance score 0-2;
  4. Histologically confirmed as CD19-positive lymphoma and who meet one of the following conditions;

    • Patient receive at least 2-4 prior combination chemotherapy regimens (not including single agent monoclonal antibody therapy) and fail to achieve CR; or have disease recurrence; or not eligible for allogeneic stem cell transplantation; or disease responding or stable after most recent therapy but refused further treatment;
    • Disease recurrence after stem cell transplantation;
    • Diagnosis as lymphoma, but refuse conventional treatment such as chemotherapy, radiation, stem cell transplantation and monoclonal antibody therapy
  5. Creatinine < 2.5 mg/dl;
  6. ALT/AST < 3x normal;
  7. Bilirubin < 2.0 mg/dl;
  8. Adequate venous access for apheresis, and no other contraindications for leukapheresis;
  9. Take contraceptive measures before recruit to this trial;
  10. Written voluntary informed consent is given.

Exclusion Criteria:

  1. Patients with symptoms of central nervous system
  2. Accompanied by other malignant tumor
  3. Active hepatitis B or C, HIV infection
  4. Any other diseases could affect the outcome of this trial
  5. Suffering severe cardiovascular or respiratory disease
  6. Poorly controlled hypertension
  7. A history of mental illness and poorly controlled
  8. Taking immunosuppressive agents within 1 week due to organ transplantation or other disease which need long-lasting administration
  9. Occurrence of unstable pulmonary embolism, deep vein thrombosis, or other major arterial/venous thromboembolic events 30 days prior to assignment
  10. Reaching a steady dose if receiving anticoagulant therapy before assignment
  11. Female study participants of reproductive potential must have a negative serum or urine pregnancy test performed within 48 hours before infusion
  12. Pregnant or lactating women
  13. Subject suffering disease affects the understanding of informed consent or comply with study protocol.
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: Qingzhu Jia, M.D. +(86)-152-2333-4184 jiaqingzhu0801@outlook.com
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02652910
Other Study ID Numbers  ICMJE 20151117
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Qingzhu Jia, M.D., Xinqiao Hospital of Chongqing
Study Sponsor  ICMJE Xinqiao Hospital of Chongqing
Collaborators  ICMJE
  • Xuzhou Medical University
  • Hrain Biotechnology Co., Ltd.
  • Shanghai Changzheng Hospital
Investigators  ICMJE
Principal Investigator: Bo Zhu, M.D., Ph.D. Department of Cancer of Xinqiao Hospital
PRS Account Xinqiao Hospital of Chongqing
Verification Date April 2016

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