Back to resultsMemory-enriched CAR-T Cells Immunotherapy for B Cell Lymphoma (MeCAR)
Primary Purpose
Recurrent Adult Diffuse Large Cell Lymphoma, Recurrent Follicular Lymphoma, Recurrent Mantle Cell Lymphoma
Status
Unknown status
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
CD19.CAR-T cells
Sponsored by
About this trial
This is an interventional treatment trial for Recurrent Adult Diffuse Large Cell Lymphoma
Eligibility Criteria
Inclusion Criteria:
- 18 Years to 70 Years, Male and female;
- Expected survival > 12 weeks;
- Performance score 0-2;
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
- Creatinine < 2.5 mg/dl;
- ALT/AST < 3x normal;
- Bilirubin < 2.0 mg/dl;
- Adequate venous access for apheresis, and no other contraindications for leukapheresis;
- Take contraceptive measures before recruit to this trial;
- Written voluntary informed consent is given.
Exclusion Criteria:
- Patients with symptoms of central nervous system
- Accompanied by other malignant tumor
- Active hepatitis B or C, HIV infection
- Any other diseases could affect the outcome of this trial
- Suffering severe cardiovascular or respiratory disease
- Poorly controlled hypertension
- A history of mental illness and poorly controlled
- Taking immunosuppressive agents within 1 week due to organ transplantation or other disease which need long-lasting administration
- Occurrence of unstable pulmonary embolism, deep vein thrombosis, or other major arterial/venous thromboembolic events 30 days prior to assignment
- Reaching a steady dose if receiving anticoagulant therapy before assignment
- Female study participants of reproductive potential must have a negative serum or urine pregnancy test performed within 48 hours before infusion
- Pregnant or lactating women
- Subject suffering disease affects the understanding of informed consent or comply with study protocol.
Sites / Locations
- Department of OncologyRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
IL-2 programmed CD19.CAR-T cells
IL-7/IL-15 programmed CD19.CAR-T cells
Arm Description
Administrated with IL-2 programmed CD19.CAR-T cells on day 0,1,2 in the lympho-depleted patients
Administrated with IL-7/IL-15 programmed CD19.CAR-T cells on day 0,1,2 in the lympho-depleted patients
Outcomes
Primary Outcome Measures
Phase 1: Safety measured by occurrence of study related adverse effects defined by NCI CTCAE 4.0
Phase 2: Overall complete remission rate defined by the standard response criteria for malignant lymphoma for each arm
Phase 2: Comparison of overall complete remission rate for the two arms
Secondary Outcome Measures
Duration of remission
Minimum residual disease negative remission rate
Duration of CAR-positive T cells in circulation
Total number of CAR-positive T cells infiltrated into lymphoma tissue
Overall survival
Full Information
NCT ID
NCT02652910
First Posted
November 18, 2015
Last Updated
February 25, 2019
Sponsor
Xinqiao Hospital of Chongqing
Collaborators
Xuzhou Medical University, Hrain Biotechnology Co., Ltd., Shanghai Changzheng Hospital
1. Study Identification
Unique Protocol Identification Number
NCT02652910
Brief Title
Memory-enriched CAR-T Cells Immunotherapy for B Cell Lymphoma
Acronym
MeCAR
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
April 2016
Overall Recruitment Status
Unknown status
Study Start Date
December 2015 (undefined)
Primary Completion Date
June 2019 (Anticipated)
Study Completion Date
December 2019 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Xinqiao Hospital of Chongqing
Collaborators
Xuzhou Medical University, Hrain Biotechnology Co., Ltd., Shanghai Changzheng Hospital
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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
To determine the safety and feasibility of CD19.CAR-T cells manufactured through IL-7/IL-15-mediated expansion or IL-2-mediated expansion
To determine in vivo dynamics and persistency of IL-7/IL-15 programmed CD19.CAR-T cells.
To determine the efficacy of IL-7/IL-15 programmed CD19.CAR-T cells in treating patients with CD19-positive lymphoma
Secondary Objectives
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
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
To assess the dynamics of intratumoral infiltration of CD19.CAR-T cells.
To correlate the subsets and differentiation of CD19.CAR-T cells to observed anti-tumor efficacy
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
20 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
IL-2 programmed CD19.CAR-T cells
Arm Type
Experimental
Arm Description
Administrated with IL-2 programmed CD19.CAR-T cells on day 0,1,2 in the lympho-depleted patients
Arm Title
IL-7/IL-15 programmed CD19.CAR-T cells
Arm Type
Experimental
Arm Description
Administrated with IL-7/IL-15 programmed CD19.CAR-T cells on day 0,1,2 in the lympho-depleted patients
Intervention Type
Drug
Intervention Name(s)
CD19.CAR-T cells
Other Intervention Name(s)
DSCAR01
Intervention Description
Retroviral vector-transduced autologous T cells to express CD19-specific CARs
Primary Outcome Measure Information:
Title
Phase 1: Safety measured by occurrence of study related adverse effects defined by NCI CTCAE 4.0
Time Frame
4 weeks
Title
Phase 2: Overall complete remission rate defined by the standard response criteria for malignant lymphoma for each arm
Time Frame
8 weeks
Title
Phase 2: Comparison of overall complete remission rate for the two arms
Time Frame
One year
Secondary Outcome Measure Information:
Title
Duration of remission
Time Frame
One year
Title
Minimum residual disease negative remission rate
Time Frame
8 weeks
Title
Duration of CAR-positive T cells in circulation
Time Frame
6 months
Title
Total number of CAR-positive T cells infiltrated into lymphoma tissue
Time Frame
6 months
Title
Overall survival
Time Frame
One year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
18 Years to 70 Years, Male and female;
Expected survival > 12 weeks;
Performance score 0-2;
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
Creatinine < 2.5 mg/dl;
ALT/AST < 3x normal;
Bilirubin < 2.0 mg/dl;
Adequate venous access for apheresis, and no other contraindications for leukapheresis;
Take contraceptive measures before recruit to this trial;
Written voluntary informed consent is given.
Exclusion Criteria:
Patients with symptoms of central nervous system
Accompanied by other malignant tumor
Active hepatitis B or C, HIV infection
Any other diseases could affect the outcome of this trial
Suffering severe cardiovascular or respiratory disease
Poorly controlled hypertension
A history of mental illness and poorly controlled
Taking immunosuppressive agents within 1 week due to organ transplantation or other disease which need long-lasting administration
Occurrence of unstable pulmonary embolism, deep vein thrombosis, or other major arterial/venous thromboembolic events 30 days prior to assignment
Reaching a steady dose if receiving anticoagulant therapy before assignment
Female study participants of reproductive potential must have a negative serum or urine pregnancy test performed within 48 hours before infusion
Pregnant or lactating women
Subject suffering disease affects the understanding of informed consent or comply with study protocol.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Qingzhu Jia, M.D.
Phone
+(86)-152-2333-4184
Email
jiaqingzhu0801@outlook.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bo Zhu, M.D., Ph.D.
Organizational Affiliation
Department of Cancer of Xinqiao Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Oncology
City
ChongQing
State/Province
Chongqing
ZIP/Postal Code
400000
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Qingzhu Jia, MD
Phone
152-2333-4184
Ext
+86
Email
jiaqinghzu0801@outlook.com
12. IPD Sharing Statement
Citations:
PubMed Identifier
34515338
Citation
Ernst M, Oeser A, Besiroglu B, Caro-Valenzuela J, Abd El Aziz M, Monsef I, Borchmann P, Estcourt LJ, Skoetz N, Goldkuhle M. Chimeric antigen receptor (CAR) T-cell therapy for people with relapsed or refractory diffuse large B-cell lymphoma. Cochrane Database Syst Rev. 2021 Sep 13;9(9):CD013365. doi: 10.1002/14651858.CD013365.pub2.
Results Reference
derived
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Memory-enriched CAR-T Cells Immunotherapy for B Cell Lymphoma
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