BCMA-CD19 cCAR T Cell Treatment of Relapsed/Refractory Systemic Lupus Erythematosus (SLE)
Primary Purpose
Relapsed/Refractory, Systemic Lupus Erythematosus (SLE)
Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
BCMA-CD19 cCAR T cells
Sponsored by
About this trial
This is an interventional treatment trial for Relapsed/Refractory, Systemic Lupus Erythematosus (SLE) focused on measuring BCMA-CA19 CAR, lupus, SLE, systemic lupus erythematosus, autoimmune disorders
Eligibility Criteria
Inclusion Criteria:
- Age: 18~65 years old;
- Expected survival period ≥ 3 months;
- Serum creatinine <221.0μmol/L (2.5mg/dl);
- AST/ALT below 3 times the upper limit of normal, blood bilirubin <34.2 μmol/L (2.0 mg/dl);
- Cardiopulmonary function is basically normal, echocardiography indicates that the ejection fraction is >50%, and the oxygen saturation is above 94% in the resting state without oxygen;
- No obvious active infection;
- Physical fitness score 0~2 points (ECOG standard);
- There are suitable veins for blood cell apheresis or whole blood collection, and there are no contraindications for blood collection;
- Since the effect of CAR T cell therapy on the fetus is unknown, women of childbearing age should have a negative serum or urine pregnancy test 48 hours before CAR T cell reinfusion, and agree to take effective measures during the trial until the last follow-up. contraceptive measures;
- Voluntary participation and informed consent signed by the patient or his/her legal/authorized representative.
Exclusion Criteria:
- Severe systemic lupus erythematosus: BILAG score at least 1 system is A and (or) >2 systems reach B, or SELENA SLEDAI>12 points.
- CNS disease: Active central nervous system (CNS) lupus (including epilepsy, psychosis, organic encephalopathy syndrome, cerebrovascular accident [CVA], encephalitis or CNS vasculitis), visual Disorders, cranial neuropathy requiring intervention
- Abnormal liver function: aspartate transaminase (AST) or alanine transaminase (ALT) or glutamyl transpeptidase (GGT) detection value is greater than 3 times the upper limit of normal (ULN); or alkaline phosphatase ( ALP) or total bilirubin test value greater than 1.5 times the upper limit of normal (ULN);
- Kidney disease: hemodialysis or high-dose glucocorticoid treatment is required within 90 days before visit 2, such as prednisone (or equivalent dose of glucocorticoid) ≥ 100 mg/d, or creatinine (Cr) or blood urea nitrogen (BUN) detection value greater than 1.5 times the upper limit of normal (ULN), or eGFR ≤ 60ml/min before visit 2. eGFR is calculated using the MDRD formula: eGFR (ml/min×1.73m^2)=186×serum creatinine (Scr)-1.154×age-0.203× (multiply by 0.724 if the subject is a female)
- Cardiovascular disease: history of acute myocardial infarction, or unstable angina pectoris, severe arrhythmia (multi-source frequent premature ventricular tachycardia, ventricular tachycardia, ventricular fibrillation) in the past 6 months; New York heart function class (NYHA) class III- Level IV
- Other uncontrolled diseases: acute or chronic diseases (such as acute pneumonia, pulmonary hypertension, diabetic ketoacidosis, acute pancreatitis, etc.) that are clinically unstable or have not been effectively controlled and are not related to SLE. judgments that may confound study results or place subjects at undue risk.
- Infection: Subject has acute or chronic infection requiring treatment (eg, tuberculosis, pneumocystis, cytomegalovirus, herpes simplex virus, herpes zoster, and atypical mycobacteria)
- Surgery or other conditions: planning to undergo surgery or have any other medical history (eg, recent history of sepsis), abnormal laboratory tests, or other conditions, judged by the investigator to be inappropriate to participate in this study
- Biologics therapy: Received any drug therapy (antibody, inhibitor or agonist) targeting T, B lymphocytes, cytokines or receptors within two months
- Participated in any clinical study within 3 months prior to enrollment
- The use of contraindicated drugs or therapies may affect the judgment of the efficacy of CART: 1) Received any of the following treatments within 90 days before Visit 2: (1) Intravenous immune globulin (IVIG); (2) Oral high-dose glucocorticoids Hormones, such as prednisone >100mg/d; (3) plasma exchange, leukotomy; 2) new immunosuppressive/immune modulators were added within 60 days before visit 2, and the disease is still under control.
- Received live vaccine treatment within 30 days prior to Visit 2
- Transplantation: History of vital organ transplantation (eg, heart, lung, kidney, liver) or hematopoietic stem cell/or bone marrow transplantation
- HIV positive.
- Active hepatitis B or C.
- Suffering from malignant tumors of other organs at the same time.
- Pregnant or lactating women.
- Inability to understand or follow the research protocol.
- Participate in other clinical investigators during the same period.
- Have any other clinically significant disease history or current disease that, in the judgment of the research physician, may pose a risk to the safety of the subjects, or interfere with the completion of the research procedure and the evaluation of safety and efficacy.
Sites / Locations
- Zhongshan People's HospitalRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
BCMA-CD19 cCAR T cells
Arm Description
Dose escalation phase: patient's T cells will be transduced with a lentiviral vector to express a BCMA-CD19 cCAR. with an escalation approach.
Outcomes
Primary Outcome Measures
The number and incidence of adverse events after BCMA-CD19 cCAR T cell infusion
Evaluation all possible adverse reactions, including the number, incidence, and severity of symptoms such as cytokine release syndromes and neurotoxicity within 3 months after CAR infusion.
Secondary Outcome Measures
Autoantibody detection
Autoantibody detection up to 6 months after BCMA-CD19 cCAR T cells infusion
SLEAI score
SLEAI score taken up to 2 years after BCMA-CD19 cCAR T cells infusion
Renal functions
Renal functions monitored up to 1years after BCMA-CD19 cCAR T cells infusion
Disease control
Disease control monitored up to 2 years after BCMA-CD19 cCAR T cells infusion)
Overall survival
Overall survival (2 year after CAR infusion). The time from the start of BCMA-CD19 cCAR infusion to death is determined as the overall survival
Full Information
NCT ID
NCT05474885
First Posted
July 23, 2022
Last Updated
July 23, 2022
Sponsor
iCell Gene Therapeutics
Collaborators
iCAR Bio Therapeutics Ltd. China
1. Study Identification
Unique Protocol Identification Number
NCT05474885
Brief Title
BCMA-CD19 cCAR T Cell Treatment of Relapsed/Refractory Systemic Lupus Erythematosus (SLE)
Official Title
BCMA-CD19 cCAR T Cell Treatment of Relapsed/Refractory Systemic Lupus Erythematosus (SLE)
Study Type
Interventional
2. Study Status
Record Verification Date
April 2022
Overall Recruitment Status
Recruiting
Study Start Date
April 1, 2022 (Actual)
Primary Completion Date
April 30, 2025 (Anticipated)
Study Completion Date
April 30, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
iCell Gene Therapeutics
Collaborators
iCAR Bio Therapeutics Ltd. China
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
This is a phase I, interventional, single arm, open label, treatment study to evaluate the safety and tolerability of BCMA-CD19 cCAR T cells in patients with relapsed and/or refractory SLE.
Detailed Description
Systemic lupus erythematous (SLE) is a chronic diffuse connective tissue disease with unexplained etiology that can involve multiple systems in the body. SLE is considered as an incurable disease and traditional SLE treatment aims at long-term remission. Glucocorticoids combined with immunosuppressive agents are still the main treatment strategies. Recently, biological agents targeting abnormal immune cells, such as rituximab and belimumab, which deplete B cells have also achieved some success in the treatment of SLE. However, these agents cannot permanently reverse the production of abnormal antibodies as they are unable to eliminate pathogenic long-lived plasma cells. The BCMA-CD19 CAR T-cells are designed to deplete antibody-producing 'root", B cells and plasma cells.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Relapsed/Refractory, Systemic Lupus Erythematosus (SLE)
Keywords
BCMA-CA19 CAR, lupus, SLE, systemic lupus erythematosus, autoimmune disorders
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
15 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
BCMA-CD19 cCAR T cells
Arm Type
Experimental
Arm Description
Dose escalation phase: patient's T cells will be transduced with a lentiviral vector to express a BCMA-CD19 cCAR. with an escalation approach.
Intervention Type
Biological
Intervention Name(s)
BCMA-CD19 cCAR T cells
Intervention Description
BCMA-CD19 cCAR T cells are used to treat patients. Patient will be administered either fresh or thawed CAR T cells by IV injection after receiving lymphodepleting chemotherapy.
Primary Outcome Measure Information:
Title
The number and incidence of adverse events after BCMA-CD19 cCAR T cell infusion
Description
Evaluation all possible adverse reactions, including the number, incidence, and severity of symptoms such as cytokine release syndromes and neurotoxicity within 3 months after CAR infusion.
Time Frame
3 months after CAR infusion
Secondary Outcome Measure Information:
Title
Autoantibody detection
Description
Autoantibody detection up to 6 months after BCMA-CD19 cCAR T cells infusion
Time Frame
6 months after CAR infusion
Title
SLEAI score
Description
SLEAI score taken up to 2 years after BCMA-CD19 cCAR T cells infusion
Time Frame
2 years after CAR infusion
Title
Renal functions
Description
Renal functions monitored up to 1years after BCMA-CD19 cCAR T cells infusion
Time Frame
1 year after CAR infusion
Title
Disease control
Description
Disease control monitored up to 2 years after BCMA-CD19 cCAR T cells infusion)
Time Frame
2 years after CAR infusion
Title
Overall survival
Description
Overall survival (2 year after CAR infusion). The time from the start of BCMA-CD19 cCAR infusion to death is determined as the overall survival
Time Frame
2 years after CAR infusion
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age: 18~65 years old;
Expected survival period ≥ 3 months;
Serum creatinine <221.0μmol/L (2.5mg/dl);
AST/ALT below 3 times the upper limit of normal, blood bilirubin <34.2 μmol/L (2.0 mg/dl);
Cardiopulmonary function is basically normal, echocardiography indicates that the ejection fraction is >50%, and the oxygen saturation is above 94% in the resting state without oxygen;
No obvious active infection;
Physical fitness score 0~2 points (ECOG standard);
There are suitable veins for blood cell apheresis or whole blood collection, and there are no contraindications for blood collection;
Since the effect of CAR T cell therapy on the fetus is unknown, women of childbearing age should have a negative serum or urine pregnancy test 48 hours before CAR T cell reinfusion, and agree to take effective measures during the trial until the last follow-up. contraceptive measures;
Voluntary participation and informed consent signed by the patient or his/her legal/authorized representative.
Exclusion Criteria:
Severe systemic lupus erythematosus: BILAG score at least 1 system is A and (or) >2 systems reach B, or SELENA SLEDAI>12 points.
CNS disease: Active central nervous system (CNS) lupus (including epilepsy, psychosis, organic encephalopathy syndrome, cerebrovascular accident [CVA], encephalitis or CNS vasculitis), visual Disorders, cranial neuropathy requiring intervention
Abnormal liver function: aspartate transaminase (AST) or alanine transaminase (ALT) or glutamyl transpeptidase (GGT) detection value is greater than 3 times the upper limit of normal (ULN); or alkaline phosphatase ( ALP) or total bilirubin test value greater than 1.5 times the upper limit of normal (ULN);
Kidney disease: hemodialysis or high-dose glucocorticoid treatment is required within 90 days before visit 2, such as prednisone (or equivalent dose of glucocorticoid) ≥ 100 mg/d, or creatinine (Cr) or blood urea nitrogen (BUN) detection value greater than 1.5 times the upper limit of normal (ULN), or eGFR ≤ 60ml/min before visit 2. eGFR is calculated using the MDRD formula: eGFR (ml/min×1.73m^2)=186×serum creatinine (Scr)-1.154×age-0.203× (multiply by 0.724 if the subject is a female)
Cardiovascular disease: history of acute myocardial infarction, or unstable angina pectoris, severe arrhythmia (multi-source frequent premature ventricular tachycardia, ventricular tachycardia, ventricular fibrillation) in the past 6 months; New York heart function class (NYHA) class III- Level IV
Other uncontrolled diseases: acute or chronic diseases (such as acute pneumonia, pulmonary hypertension, diabetic ketoacidosis, acute pancreatitis, etc.) that are clinically unstable or have not been effectively controlled and are not related to SLE. judgments that may confound study results or place subjects at undue risk.
Infection: Subject has acute or chronic infection requiring treatment (eg, tuberculosis, pneumocystis, cytomegalovirus, herpes simplex virus, herpes zoster, and atypical mycobacteria)
Surgery or other conditions: planning to undergo surgery or have any other medical history (eg, recent history of sepsis), abnormal laboratory tests, or other conditions, judged by the investigator to be inappropriate to participate in this study
Biologics therapy: Received any drug therapy (antibody, inhibitor or agonist) targeting T, B lymphocytes, cytokines or receptors within two months
Participated in any clinical study within 3 months prior to enrollment
The use of contraindicated drugs or therapies may affect the judgment of the efficacy of CART: 1) Received any of the following treatments within 90 days before Visit 2: (1) Intravenous immune globulin (IVIG); (2) Oral high-dose glucocorticoids Hormones, such as prednisone >100mg/d; (3) plasma exchange, leukotomy; 2) new immunosuppressive/immune modulators were added within 60 days before visit 2, and the disease is still under control.
Received live vaccine treatment within 30 days prior to Visit 2
Transplantation: History of vital organ transplantation (eg, heart, lung, kidney, liver) or hematopoietic stem cell/or bone marrow transplantation
HIV positive.
Active hepatitis B or C.
Suffering from malignant tumors of other organs at the same time.
Pregnant or lactating women.
Inability to understand or follow the research protocol.
Participate in other clinical investigators during the same period.
Have any other clinically significant disease history or current disease that, in the judgment of the research physician, may pose a risk to the safety of the subjects, or interfere with the completion of the research procedure and the evaluation of safety and efficacy.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Kevin Pinz
Phone
6315386218
Email
kevin.pinz@icellgene.com
First Name & Middle Initial & Last Name or Official Title & Degree
Wei-Jia Wang, MD
Phone
011-86-13715679657
Email
wangwj@zsph.com
Facility Information:
Facility Name
Zhongshan People's Hospital
City
Zhongshan
State/Province
Guangdong
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Wei-Jia Wang, MD
Phone
011-86-13715679657
Email
wangwj@zsph.com
12. IPD Sharing Statement
Learn more about this trial
BCMA-CD19 cCAR T Cell Treatment of Relapsed/Refractory Systemic Lupus Erythematosus (SLE)
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