Clinical Trial to Evaluate CD19 CAR T (CT032) in Patients With Relapsed and/or Refractory Non-Hodgkin's B Cell Lymphoma
Primary Purpose
Refractory B-Cell Non-Hodgkin Lymphoma, Relapsed B-cell Non-Hodgkin Lymphoma
Status
Completed
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
CAR-CD19 T Cells
Sponsored by
About this trial
This is an interventional treatment trial for Refractory B-Cell Non-Hodgkin Lymphoma focused on measuring Relapsed and/or Refractory B-cell Non-Hodgkin Lymphoma, CAR T
Eligibility Criteria
Inclusion Criteria:
- The subject should participate in the clinical trial voluntarily, be fully aware of and informed of this study and sign informed consent (ICF), and be willing to follow and be able to complete all trial procedures;
- Age 18-70 years old, male or female;
- CD 19 positive, Relapsed and/or Refractory Diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma after the transformation of Relapsed and/or Refractory DLBCL subjects by histopathological and/or cytology diagnosis; At least received second-line systemic anticancer treatments containing rituximab (or other anti-CD20 drugs) and anthracene (including autologous hematopoietic stem cell transplantation) , and had progressive disease (PD) or relapse after the latest treatment.
- The Eastern Cooperative Oncology Group (ECOG) score is 0 or 1 point;
- The expected survival period is more than 12 weeks;
- Having sufficient venous pathways (for leukapheresis or intravenous blood collection) and no leukapheresis contraindications;
- At least one measurable lesion: the long axis >1.5 cm of the lymph node lesion, or the long axis >1.0 cm of the non-lymph node lesion;
- subject has adequate organ function at screening;
- Women of childbearing age must undergo a serum pregnancy test with negative results before screening and lymphodepletion preconditioning with fludarabine and cyclophosphamide, and are willing to use effective and reliable method of contraception for at least 1 year after T cell infusion;
- Male subjects who have an active sex life with a woman with reproductive potential must be willing to use very effective and reliable methods of contraception for at least 1 year after T cell infusion.
Exclusion Criteria:
If the subject meets any of the following criteria, he or she cannot participate in this trial:
- A history of severe allergies, or a history of allergies or intolerance to fludarabine, cyclophosphamide or tocilizumab, or a history of allergies or intolerance to CAR T cell cytosolic component, or a history of allergic to beta-caprolactam antibiotics;
- Received chemotherapy, targeted therapy, radiotherapy and other anti-tumor treatment within 14 days before peripheral blood mononuclear cells (PBMCs) collection;
- Previously received any target of CAR T treatment, or previously received CD19 targeted drug treatment;
- Has undergone allogeneic hematopoietic stem cell transplantation; autologous stem cell transplantation was received within 12 weeks before PBMCs collection;
- Other malignant neoplasms existed in the previous 5 years or at the same time, with the exception of breast/cervical in situ cancer, cured basal cell carcinoma and superficial bladder tumor (Ta, Tis, T1);
- Any uncontrollable active infection, including but not limited to active TB patients
- subjects who had received a therapeutic dose of systemic steroid drugs (prednisone >20mg/days or equivalent doses of other hormones) or other immunosuppressants within 7 days before PBMCs collection, with the exception of those who had recently or currently used inhaled steroids;
- Known to have active autoimmune diseases, including but not limited to psoriasis, rheumatoid arthritis, etc., that need long-term immunosuppressive therapy;
- Patients with refractory hyponatremia and/or hypokalemia;
- Known or existing primary or metastatic central nervous system lymphoma, or any other central neurological disease or clinically significant neurological examination with abnormal results (such as seizures, cerebrovascular ischemia/hemorrhage, dementia, etc.);
- Within 6 months prior to signing the ICF, there were any of the uncontrolled cardiovascular, cerebral vascular disease, diabetes and pulmonary embolism, or other disease at discretion of investigators that participating in this clinical trial may harm the health of the subjects;
- Oxygen absorption before PBMCs collection to maintain blood oxygen saturation >95% (finger vein oxygen);
- According to the investigator, any serious or uncontrollable systemic disease, systematic comorbidities, other serious concurrent diseases (such as hemophagocytic syndrome, etc.), special circumstances of the tumor may make the subjects inappropriate to enter the study or non-compliant to the protocol, or produce significant interference to correct evaluation of study drug safety, toxicity, and validity;
- The investigators assessed that the subjects were unable or unwilling to comply with the requirements of the research protocol;
- Major surgical operations were performed within 4 weeks of the group (the definition of major surgery is based on the 3 and 4 levels of surgery specified in the measures for the administration of clinical application of medical technology); or has not yet been fully recovered from any previous invasive operation;
- The toxic response of previous anti-tumor therapy has not been restored to level 1 according to the Common Terminology Criteria for Adverse Events (CTCAE), except for hair loss and;
- Having participated in any other interventional clinical trial before administration, where the last time of drug administration is within 4 weeks or less than 5 half-lives of the test drug (the longer);
- Women who have been pregnant, prepared for pregnancy during the trial, or are breastfeeding; or women of childbearing age and fertile men who are unwilling or unable to adopt medically recognized and effective contraceptive methods throughout the study period;
- The investigator or a relative of his staff, a subject who may have an interest in it with the investigator or his staff.
Sites / Locations
- Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine
- First Affiliated Hospital of Zhejiang University
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
CAR-CD19-T Cells
Arm Description
The subjects are enrolled into 3 dose levels cohorts in sequence.
Outcomes
Primary Outcome Measures
Phase Ⅰ, Safety/Tolerability: Dose-limiting toxicity (DLT)
Dose-limiting toxicity (DLT)
Phase Ⅰ, Safety/Tolerability: Maximum tolerated dose (MTD)
Maximum tolerated dose (MTD)
Phase Ⅰ, Safety/Tolerability: Incidence and severity of Treatment emergent adverse events (TEAE)
Incidence and severity of Treatment emergent adverse events (TEAE)
Phase Ⅰ, Safety/Tolerability: Incidence and severity of study treatment related AE
Incidence and severity of AE related to study treatment
Phase Ⅰ, Safety/Tolerability: Incidence and severity of AEs of special interest (cytokine release syndrome [CRS], CART-cell-related encephalopathy syndrome [CRES])
Incidence and severity of AEs of special interest (cytokine release syndrome [CRS], CART-cell-related encephalopathy syndrome [CRES])
Phase Ⅰ, Safety/Tolerability: Incidence and severity of Dose-limiting toxicity (DLT) of dose escalation experiment
Incidence and severity of Dose-limiting toxicity (DLT) of dose escalation experiment
Phase Ⅰ, Safety/Tolerability: Recommended Phase II Dose (RP2D)
Recommended Phase II Dose (RP2D)
Phase Ⅱ, Efficacy: Overall Remission Rate (ORR)
Overall Remission Rate (ORR) (Partial remission and complete remission rate after infusion of CT032 CAR-CD19 T cells)
Secondary Outcome Measures
Phase Ⅰ, Safety/Tolerability: Incidence and severity of Treatment emergent adverse events (TEAE)
Incidence and severity of Treatment emergent adverse events (TEAE)
Phase Ⅰ, Safety/Tolerability: Incidence and severity of study treatment related AE
Incidence and severity of AE related to study treatment
Phase Ⅰ, Safety/Tolerability: Cytokine (IL-2, IL-6,IL-8,IL-10,IFN-γ,TNF-α ) concentration (pg/mL) by MSD and CBA method
Cytokine (IL-2, IL-6,IL-8,IL-10,IFN-γ,TNF-α ) concentration (pg/mL) by MSD and CBA method
Phase Ⅰ: the number of copies of CAR-CD19 T cells in peripheral blood genomes by qPCR method and CAR-CD19 T cells by flow cytometry method
the number of copies of CAR-CD19 T cells in peripheral blood genomes by qPCR method and CAR-CD19 T cells by flow cytometry method
Phase Ⅰ, Efficacy: Overall Remission Rate (ORR)
Overall Remission Rate (ORR) (Partial remission and complete remission rate after infusion of CT032 CAR-CD19 T cells)
Phase Ⅱ, Efficacy: complete response (CR) rate
complete response (CR) rate
Phase Ⅱ, Efficacy: duration of response (DOR)
duration of response (DOR)
Phase Ⅱ, Efficacy: time to response (TTR)
time to response (TTR)
Phase Ⅱ, Efficacy: progression-free survival (PFS)
progression-free survival (PFS) time
Phase Ⅱ, Efficacy: overall survival (OS)
overall survival (OS) time
Phase Ⅱ, Safety/Tolerability: Incidence and severity of Treatment emergent adverse events (TEAE)
Incidence and severity of Treatment emergent adverse events (TEAE)
Incidence and severity of o study treatment related AE
Incidence and severity of AE related to study treatment
Phase Ⅱ, Safety/Tolerability: Incidence and severity of AEs of special interest (CRS, CRES)
Incidence and severity of AEs of special interest (CRS, CRES)
Phase Ⅱ, Safety/Tolerability: Cytokine (IL-2, IL-6,IL-8,IL-10,IFN-γ,TNF-α ) concentration (pg/mL) by MSD and CBA method
Cytokine (IL-2, IL-6,IL-8,IL-10,IFN-γ,TNF-α ) concentration (pg/mL) by MSD and CBA method
Phase Ⅱ: the number of copies of CAR-CD19 T cells in peripheral blood genomes by qPCR method and CAR-CD19 T cells by flow cytometry method
the number of copies of CAR-CD19 T cells in peripheral blood genomes by qPCR method and CAR-CD19 T cells by flow cytometry method
Full Information
NCT ID
NCT03994913
First Posted
June 12, 2019
Last Updated
April 13, 2023
Sponsor
CARsgen Therapeutics Co., Ltd.
Collaborators
First Affiliated Hospital of Zhejiang University, RenJi Hospital
1. Study Identification
Unique Protocol Identification Number
NCT03994913
Brief Title
Clinical Trial to Evaluate CD19 CAR T (CT032) in Patients With Relapsed and/or Refractory Non-Hodgkin's B Cell Lymphoma
Official Title
An Open, Multi-center Phase Ⅰ/II Clinical Study to Evaluate the Safety and Efficacy of CT032 Humanized CD19 Autologous Car T Cell Injection in Patients With Relapsed and/or Refractory Non-Hodgkin's B Cell Lymphoma
Study Type
Interventional
2. Study Status
Record Verification Date
April 2023
Overall Recruitment Status
Completed
Study Start Date
August 14, 2019 (Actual)
Primary Completion Date
January 20, 2021 (Actual)
Study Completion Date
May 27, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
CARsgen Therapeutics Co., Ltd.
Collaborators
First Affiliated Hospital of Zhejiang University, RenJi Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This is an open-label, single arm study to evaluate the safety and tolerability of treatment with CT032 CAR-CD19 T in patients with relapsed and/or refractory non-Hodgkin's B cell lymphoma (R/R B-NHL).
Detailed Description
This study is a single-arm, open label, phase I/II clinical trial to evaluate the safety, efficacy and cellular kinetics of CT032 CAR-CD19 T cells in patients with R/R B-NHL. The study is composed of two stages, Phase I stage is for dose escalation and recommendation of phase 2 dose, and Phase II stage is to verify the efficacy and safety of the dose proposed.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Refractory B-Cell Non-Hodgkin Lymphoma, Relapsed B-cell Non-Hodgkin Lymphoma
Keywords
Relapsed and/or Refractory B-cell Non-Hodgkin Lymphoma, CAR T
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Actual)
8. Arms, Groups, and Interventions
Arm Title
CAR-CD19-T Cells
Arm Type
Experimental
Arm Description
The subjects are enrolled into 3 dose levels cohorts in sequence.
Intervention Type
Biological
Intervention Name(s)
CAR-CD19 T Cells
Intervention Description
The CAR- CD19 T cells (study drug) used in this study are chimeric antigen receptor specifically expressing T cells targeting CD19.
Fludarabine and Cyclophosphamide are used for lymphodepletion.
Primary Outcome Measure Information:
Title
Phase Ⅰ, Safety/Tolerability: Dose-limiting toxicity (DLT)
Description
Dose-limiting toxicity (DLT)
Time Frame
28 days post administration of CAR-T cells
Title
Phase Ⅰ, Safety/Tolerability: Maximum tolerated dose (MTD)
Description
Maximum tolerated dose (MTD)
Time Frame
28 days post administration of CAR-T cells
Title
Phase Ⅰ, Safety/Tolerability: Incidence and severity of Treatment emergent adverse events (TEAE)
Description
Incidence and severity of Treatment emergent adverse events (TEAE)
Time Frame
28 days post administration of CAR-T cells
Title
Phase Ⅰ, Safety/Tolerability: Incidence and severity of study treatment related AE
Description
Incidence and severity of AE related to study treatment
Time Frame
through 2 months post administration of CAR-T cells
Title
Phase Ⅰ, Safety/Tolerability: Incidence and severity of AEs of special interest (cytokine release syndrome [CRS], CART-cell-related encephalopathy syndrome [CRES])
Description
Incidence and severity of AEs of special interest (cytokine release syndrome [CRS], CART-cell-related encephalopathy syndrome [CRES])
Time Frame
through 2 months post administration of CAR-T cells
Title
Phase Ⅰ, Safety/Tolerability: Incidence and severity of Dose-limiting toxicity (DLT) of dose escalation experiment
Description
Incidence and severity of Dose-limiting toxicity (DLT) of dose escalation experiment
Time Frame
28 days after infusion
Title
Phase Ⅰ, Safety/Tolerability: Recommended Phase II Dose (RP2D)
Description
Recommended Phase II Dose (RP2D)
Time Frame
through 2 months post administration of CAR-T cells
Title
Phase Ⅱ, Efficacy: Overall Remission Rate (ORR)
Description
Overall Remission Rate (ORR) (Partial remission and complete remission rate after infusion of CT032 CAR-CD19 T cells)
Time Frame
through 6 months post administration of CAR-T cells
Secondary Outcome Measure Information:
Title
Phase Ⅰ, Safety/Tolerability: Incidence and severity of Treatment emergent adverse events (TEAE)
Description
Incidence and severity of Treatment emergent adverse events (TEAE)
Time Frame
through 24 months post administration of CAR-T cells
Title
Phase Ⅰ, Safety/Tolerability: Incidence and severity of study treatment related AE
Description
Incidence and severity of AE related to study treatment
Time Frame
through 24 months post administration of CAR-T cells
Title
Phase Ⅰ, Safety/Tolerability: Cytokine (IL-2, IL-6,IL-8,IL-10,IFN-γ,TNF-α ) concentration (pg/mL) by MSD and CBA method
Description
Cytokine (IL-2, IL-6,IL-8,IL-10,IFN-γ,TNF-α ) concentration (pg/mL) by MSD and CBA method
Time Frame
through 24 months post administration of CAR-T-cells
Title
Phase Ⅰ: the number of copies of CAR-CD19 T cells in peripheral blood genomes by qPCR method and CAR-CD19 T cells by flow cytometry method
Description
the number of copies of CAR-CD19 T cells in peripheral blood genomes by qPCR method and CAR-CD19 T cells by flow cytometry method
Time Frame
through 24 months post administration of CAR-T cells
Title
Phase Ⅰ, Efficacy: Overall Remission Rate (ORR)
Description
Overall Remission Rate (ORR) (Partial remission and complete remission rate after infusion of CT032 CAR-CD19 T cells)
Time Frame
through 24 months post administration of CAR-T cells
Title
Phase Ⅱ, Efficacy: complete response (CR) rate
Description
complete response (CR) rate
Time Frame
through 24 months post administration of CAR-T cells
Title
Phase Ⅱ, Efficacy: duration of response (DOR)
Description
duration of response (DOR)
Time Frame
through 24 months post administration of CAR-T cells
Title
Phase Ⅱ, Efficacy: time to response (TTR)
Description
time to response (TTR)
Time Frame
through 24 months post administration of CAR-T cells
Title
Phase Ⅱ, Efficacy: progression-free survival (PFS)
Description
progression-free survival (PFS) time
Time Frame
through 24 months post administration of CAR-T cells
Title
Phase Ⅱ, Efficacy: overall survival (OS)
Description
overall survival (OS) time
Time Frame
through 24 months post administration of CAR-T cells
Title
Phase Ⅱ, Safety/Tolerability: Incidence and severity of Treatment emergent adverse events (TEAE)
Description
Incidence and severity of Treatment emergent adverse events (TEAE)
Time Frame
through 24 months post administration of CAR-T cells
Title
Incidence and severity of o study treatment related AE
Description
Incidence and severity of AE related to study treatment
Time Frame
through 24 months post administration of CAR-T cells
Title
Phase Ⅱ, Safety/Tolerability: Incidence and severity of AEs of special interest (CRS, CRES)
Description
Incidence and severity of AEs of special interest (CRS, CRES)
Time Frame
through 24 months post administration of CAR-T cells
Title
Phase Ⅱ, Safety/Tolerability: Cytokine (IL-2, IL-6,IL-8,IL-10,IFN-γ,TNF-α ) concentration (pg/mL) by MSD and CBA method
Description
Cytokine (IL-2, IL-6,IL-8,IL-10,IFN-γ,TNF-α ) concentration (pg/mL) by MSD and CBA method
Time Frame
through 24 months post administration of CAR-T cells
Title
Phase Ⅱ: the number of copies of CAR-CD19 T cells in peripheral blood genomes by qPCR method and CAR-CD19 T cells by flow cytometry method
Description
the number of copies of CAR-CD19 T cells in peripheral blood genomes by qPCR method and CAR-CD19 T cells by flow cytometry method
Time Frame
through 24 months post administration of CAR-T cells
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:
The subject should participate in the clinical trial voluntarily, be fully aware of and informed of this study and sign informed consent (ICF), and be willing to follow and be able to complete all trial procedures;
Age 18-70 years old, male or female;
CD 19 positive, Relapsed and/or Refractory Diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma after the transformation of Relapsed and/or Refractory DLBCL subjects by histopathological and/or cytology diagnosis; At least received second-line systemic anticancer treatments containing rituximab (or other anti-CD20 drugs) and anthracene (including autologous hematopoietic stem cell transplantation) , and had progressive disease (PD) or relapse after the latest treatment.
The Eastern Cooperative Oncology Group (ECOG) score is 0 or 1 point;
The expected survival period is more than 12 weeks;
Having sufficient venous pathways (for leukapheresis or intravenous blood collection) and no leukapheresis contraindications;
At least one measurable lesion: the long axis >1.5 cm of the lymph node lesion, or the long axis >1.0 cm of the non-lymph node lesion;
subject has adequate organ function at screening;
Women of childbearing age must undergo a serum pregnancy test with negative results before screening and lymphodepletion preconditioning with fludarabine and cyclophosphamide, and are willing to use effective and reliable method of contraception for at least 1 year after T cell infusion;
Male subjects who have an active sex life with a woman with reproductive potential must be willing to use very effective and reliable methods of contraception for at least 1 year after T cell infusion.
Exclusion Criteria:
If the subject meets any of the following criteria, he or she cannot participate in this trial:
A history of severe allergies, or a history of allergies or intolerance to fludarabine, cyclophosphamide or tocilizumab, or a history of allergies or intolerance to CAR T cell cytosolic component, or a history of allergic to beta-caprolactam antibiotics;
Received chemotherapy, targeted therapy, radiotherapy and other anti-tumor treatment within 14 days before peripheral blood mononuclear cells (PBMCs) collection;
Previously received any target of CAR T treatment, or previously received CD19 targeted drug treatment;
Has undergone allogeneic hematopoietic stem cell transplantation; autologous stem cell transplantation was received within 12 weeks before PBMCs collection;
Other malignant neoplasms existed in the previous 5 years or at the same time, with the exception of breast/cervical in situ cancer, cured basal cell carcinoma and superficial bladder tumor (Ta, Tis, T1);
Any uncontrollable active infection, including but not limited to active TB patients
subjects who had received a therapeutic dose of systemic steroid drugs (prednisone >20mg/days or equivalent doses of other hormones) or other immunosuppressants within 7 days before PBMCs collection, with the exception of those who had recently or currently used inhaled steroids;
Known to have active autoimmune diseases, including but not limited to psoriasis, rheumatoid arthritis, etc., that need long-term immunosuppressive therapy;
Patients with refractory hyponatremia and/or hypokalemia;
Known or existing primary or metastatic central nervous system lymphoma, or any other central neurological disease or clinically significant neurological examination with abnormal results (such as seizures, cerebrovascular ischemia/hemorrhage, dementia, etc.);
Within 6 months prior to signing the ICF, there were any of the uncontrolled cardiovascular, cerebral vascular disease, diabetes and pulmonary embolism, or other disease at discretion of investigators that participating in this clinical trial may harm the health of the subjects;
Oxygen absorption before PBMCs collection to maintain blood oxygen saturation >95% (finger vein oxygen);
According to the investigator, any serious or uncontrollable systemic disease, systematic comorbidities, other serious concurrent diseases (such as hemophagocytic syndrome, etc.), special circumstances of the tumor may make the subjects inappropriate to enter the study or non-compliant to the protocol, or produce significant interference to correct evaluation of study drug safety, toxicity, and validity;
The investigators assessed that the subjects were unable or unwilling to comply with the requirements of the research protocol;
Major surgical operations were performed within 4 weeks of the group (the definition of major surgery is based on the 3 and 4 levels of surgery specified in the measures for the administration of clinical application of medical technology); or has not yet been fully recovered from any previous invasive operation;
The toxic response of previous anti-tumor therapy has not been restored to level 1 according to the Common Terminology Criteria for Adverse Events (CTCAE), except for hair loss and;
Having participated in any other interventional clinical trial before administration, where the last time of drug administration is within 4 weeks or less than 5 half-lives of the test drug (the longer);
Women who have been pregnant, prepared for pregnancy during the trial, or are breastfeeding; or women of childbearing age and fertile men who are unwilling or unable to adopt medically recognized and effective contraceptive methods throughout the study period;
The investigator or a relative of his staff, a subject who may have an interest in it with the investigator or his staff.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jie Jin, Dr.
Organizational Affiliation
First Affiliated Hospital of Zhejiang University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200127
Country
China
Facility Name
First Affiliated Hospital of Zhejiang University
City
Hangzhou
State/Province
Zhejiang
ZIP/Postal Code
310003
Country
China
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Clinical Trial to Evaluate CD19 CAR T (CT032) in Patients With Relapsed and/or Refractory Non-Hodgkin's B Cell Lymphoma
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