Back to resultsAnti-CD22 CAR-T Therapy for CD19-refractory or Resistant Lymphoma Patients (MendCART)
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
Retroviral vector-transduced autologous T cells to express CD22-specific CARs
Sponsored by
About this trial
This is an interventional treatment trial for Recurrent Adult Diffuse Large Cell Lymphoma
Eligibility Criteria
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.
11.Refractory ot resistant to prior anti-CD19 CAR-Ts
12.At least one evaluable CD22-positive recurrent lesion, confirmed by two independent pathologist.
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 Oncology, Xinqiao HospitalRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Anti-CD22 CAR-T
Arm Description
Administrated with CD22.CAR-T cells on day 0,1,2 in the lympho-depleted patients
Outcomes
Primary Outcome Measures
Safety measured by occurrence of study related adverse effects defined by NCI CTCAE 4.0
Secondary Outcome Measures
Overall complete remission rate defined by the standard response criteria for malignant lymphoma for each arm
Duration of CAR-positive T cells in circulation
Total number of CAR-positive T cells infiltrated into lymphoma tissue
Full Information
NCT ID
NCT02721407
First Posted
March 23, 2016
Last Updated
March 8, 2017
Sponsor
Xinqiao Hospital of Chongqing
Collaborators
Xuzhou Medical University
1. Study Identification
Unique Protocol Identification Number
NCT02721407
Brief Title
Anti-CD22 CAR-T Therapy for CD19-refractory or Resistant Lymphoma Patients
Acronym
MendCART
Official Title
A Phase I Study of Anti-CD22:TCRz:4-1BB T-cells in Patient With CD22-Positive Recurrent Lymphoma That is Resistant or Refractory to Prior Anti-CD22:TCRz:CD28 Immunotherapy
Study Type
Interventional
2. Study Status
Record Verification Date
March 2017
Overall Recruitment Status
Unknown status
Study Start Date
March 2016 (undefined)
Primary Completion Date
December 2018 (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
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The goal of this clinical trial is to study the feasibility and efficacy of anti-CD22:TCRz:4-1BB chimeric antigen receptor (CAR)-modified T (CAR-T) cells in treating recurrent patients with refractory or resistant lymphoma to anti-CD19:TCRz:CD28 CAR-T cells. 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 recession of evaluable lesions, the persistence and efficacy of CAR-T cells are still restricted by the "target" selection. Previous clinical studies largely utilized CD19 for the in vivo targeting of CAR-T cells, which preferentially become refractory or resistant due to the heterogeneity of lymphoma. This clinical investigation is to test a hypothesis whether anti-CD22 CAR-T cells work more effective in lymphoma patients refractory or resistent to anti-CD19:TCRz:CD28 CAR-T cells.
Detailed Description
Primary Objectives
To determine the safety of CD22.CAR-T cells in lymphoma patients refractory or resistent to anti-CD19:TCRz:CD28 CAR-T cells
To determine in vivo dynamics and persistency of CD22.CAR-T cells.
Secondary Objectives
To determine the feasibility of CD22.CAR-T cells in lymphoma patients refractory or resistent to anti-CD19:TCRz:CD28 CAR-T cells
To determine in vivo dynamics and persistency of CD22.CAR-T cells.
To assess the intratumoral infiltration of CD22.CAR-T cells.
To correlate the subsets and differentiation of CD22.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/IV Adult Diffuse Large Cell Lymphoma, Stage III/IV Follicular Lymphoma, Stage III/IV Mantle Cell Lymphoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Anti-CD22 CAR-T
Arm Type
Experimental
Arm Description
Administrated with CD22.CAR-T cells on day 0,1,2 in the lympho-depleted patients
Intervention Type
Drug
Intervention Name(s)
Retroviral vector-transduced autologous T cells to express CD22-specific CARs
Primary Outcome Measure Information:
Title
Safety measured by occurrence of study related adverse effects defined by NCI CTCAE 4.0
Time Frame
4 Weeks
Secondary Outcome Measure Information:
Title
Overall complete remission rate defined by the standard response criteria for malignant lymphoma for each arm
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
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:
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.
11.Refractory ot resistant to prior anti-CD19 CAR-Ts
12.At least one evaluable CD22-positive recurrent lesion, confirmed by two independent pathologist.
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.
Facility Information:
Facility Name
Department of Oncology, Xinqiao Hospital
City
ChongQing
State/Province
Chongqing
ZIP/Postal Code
400037
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
Plan to Share IPD
Yes
Learn more about this trial
Anti-CD22 CAR-T Therapy for CD19-refractory or Resistant Lymphoma Patients
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