A Clinical Study on the Safety and Efficacy of Chimeric Antigen Receptor T-cell (CART) in the Treatment of Solid Tumors
Study Details
Study Description
Brief Summary
This is a single-arm, investigator-initiated exploratory study.The study is designed to evaluate the safety and the tolerability of HER2-E-CART cells for the treatment of patients with HER2-positive, refractory advanced solid tumors in three dose groups: low, medium and high.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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N/A |
Detailed Description
This study was a one-arm,investigator-initiated exploratory study. According to the "3+3" principle, three dose groups with increasing dose were set up, namely low, medium and high dose groups, with separate cell counts. A total of 9-12 subjects were enrolled in the group and given intravenous infusion. Dose-limited toxicity was observed from the beginning of preconditioning to 28 days after CAR T infusion.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: HER2-E-CART cells HER2-E-CART cells were intravenously transfused and followed up to 2 years after the last cell transfusion |
Biological: HER2-E-CART cells
E-CAR-T is a novel second-generation CAR-T product targeting HER2 protein
|
Outcome Measures
Primary Outcome Measures
- Occurence of Adverse event rate [Adverse events will be collected from the beginning to the end of the study, up to 2 years after the last cell transfusion]
The occurrence of all adverse events (AEs), serious adverse events (SAEs) and treatment-related adverse events (TEAEs).
Secondary Outcome Measures
- Time to peak of serum cytokine Interleukin-2 [Within 72 hours before lymphodepletion pretreatment, within 24 hours before and 1 hour after reinfusion, 24 hours, Day 4, Day 7, Day 10, Day 14, Day 28, Day 60, Day 90, Day 180, Day 270, Day 360.]
Time to peak of serum cytokine Interleukin-2
- Time to peak of serum cytokine Interleukin-6 [Within 72 hours before lymphodepletion pretreatment, within 24 hours before and 1 hour after reinfusion, 24 hours, Day 4, Day 7, Day 10, Day 14, Day 28, Day 60, Day 90, Day 180, Day 270, Day 360.]
Time to peak of serum cytokine Interleukin-6
- Time to peak of serum cytokine Interleukin-10 [Within 72 hours before lymphodepletion pretreatment, within 24 hours before and 1 hour after reinfusion, 24 hours, Day 4, Day 7, Day 10, Day 14, Day 28, Day 60, Day 90, Day 180, Day 270, Day 360.]
Time to peak of serum cytokine Interleukin-10
- Time to peak of serum cytokine Tumor Necrosis Factor-α [Within 72 hours before lymphodepletion pretreatment, within 24 hours before and 1 hour after reinfusion, 24 hours, Day 4, Day 7, Day 10, Day 14, Day 28, Day 60, Day 90, Day 180, Day 270, Day 360.]
Time to peak of serum cytokine Tumor Necrosis Factor-α
- Time to peak of serum cytokine Tumor Necrosis Factor-γ [Within 72 hours before lymphodepletion pretreatment, within 24 hours before and 1 hour after reinfusion, 24 hours, Day 4, Day 7, Day 10, Day 14, Day 28, Day 60, Day 90, Day 180, Day 270, Day 360.]
Time to peak of serum cytokine Tumor Necrosis Factor-γ
- Overall survival (OS) [Baseline up to death event.]
From randomization to the time of death from any cause
- Objective Response Rate (ORR) [Baseline up to 144 weeks]
The proportion of patients with tumor size reduction of a predefined amount and for a minimum time period
- Disease Control Rate (DCR) [Baseline up to 144 weeks]
The percentage of patients with advanced or metastatic cancer who have achieved complete response (CR), partial response (PR) and stable disease (SD) to a cancer treatment in clinical trials
- Duration of Response (DOR) [Baseline up to 144 weeks]
The time from the date of first documentation of a CR or PR or PD to the date of first documentation of tumor progression.
- Progression Free Survival (PFS) [Baseline up to 144 weeks]
The time from the first dose to the first documentation of progressive disease (PD) or death from any cause,whichever occurs first
- Effects on subjects' health-related quality of life [Baseline up to 144 weeks]
Quality of life related scale ，for questions 1 to 28, choose a number from 1 to 4, 1 means none and 4 means very good. For questions 29 and 30, choose a number from 1 to 7, with 1 being very poor and 7 being very good.
- Peak concentration (Cmax) [Within 72 hours before lymphodepletion pretreatment, within 24 hours before and 1 hour after reinfusion, 24 hours, Day 4, Day 7, Day 10, Day 14, Day 28, Day 60, Day 90, Day 180, Day 270, Day 360.]
Maximum plasma drug concentration
- Area Under The Curve（AUC） [Within 72 hours before lymphodepletion pretreatment, within 24 hours before and 1 hour after reinfusion, 24 hours, Day 4, Day 7, Day 10, Day 14, Day 28, Day 60, Day 90, Day 180, Day 270, Day 360.]
Area under the plasma concentration-time curve Single dose
- Time to Maximum Plasma Concentration（Tmax） [Within 72 hours before lymphodepletion pretreatment, within 24 hours before and 1 hour after reinfusion, 24 hours, Day 4, Day 7, Day 10, Day 14, Day 28, Day 60, Day 90, Day 180, Day 270, Day 360.]
The time required to reach peak concentration after administration
- Elimination half-life (t1/2)-Single dose [Within 72 hours before lymphodepletion pretreatment, within 24 hours before and 1 hour after reinfusion, 24 hours, Day 4, Day 7, Day 10, Day 14, Day 28, Day 60, Day 90, Day 180, Day 270, Day 360.]
t1/2 is time it takes for the blood concentration of HER2-E-CART cells or metabolite(s) to drop by half
Eligibility Criteria
Criteria
Inclusion Criteria:
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Voluntarily signed an informed consent form and were able to complete the study procedures and follow-up examinations and treatment
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Age ≥ 18 years and ≤ 70 years, regardless of gender
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Weight > 40 kg
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Eastern Cooperative Oncology Group (ECOG) physical status score of 0 to 1
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Patients with refractory advanced solid tumors who have failed or are intolerant of existing standard regimens or whose patients have refused standard regimens
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The presence of at least one measurable lesion according to Response Evaluation Criteria In Solid Tumors 1.1 criteria
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With good organ function
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Positive HER2 cell membrane expression
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Women of childbearing potential must have a pregnancy test with negative results within 7 days prior to initiation of treatment
Exclusion Criteria:
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Any systemic antitumor therapy within 2 weeks prior to the single blood collection
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History of organ transplantation
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Pregnant or lactating women
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Uncontrolled infectious disease, such as baseline Hepatitis B Virus DNA ≥ 1000 IU/ml, anti-HIV positive, Hepatitis C Virus-RNA positive
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Other clinically significant active infections
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Other active malignancies within the previous 5 years, such as basal or squamous skin cancer, superficial bladder cancer, or in situ breast cancer that has been completely cured and does not require follow-up treatment subjects are not included
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Patients with severe autoimmune or immunodeficiency diseases, such as subjects with a confirmed diagnosis of a severe autoimmune disease requiring systemic immunosuppressive (steroid) therapy for a prolonged period of time (more than 2 months) or with immune-mediated symptomatic diseases, including ulcerative colitis, Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus (SLE), autoimmune vasculitis (e.g., Wegener's granulomatosis), etc
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Subjects with known severe allergic reactions to pretreatment drugs such as injectable cyclophosphamide, injectable paclitaxel (albumin-bound), or CAR-T cell preparations including adjuvants, dimethylsulfoxide
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Any unstable systemic disease: including but not limited to unstable angina pectoris, cerebrovascular accident or transient ischemia (within 6 months prior to screening), myocardial infarction (within 6 months prior to screening), New York Heart Association (NYHA) classification ≥ Class III congestive heart failure, severe arrhythmias poorly controlled by medications, liver, kidney or metabolic disease, and hypertension uncontrolled by standard therapy 10
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Those with active bleeding, thrombotic disorders requiring treatment
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Patients with pericardial, thoracic, or abdominal effusions requiring clinical management or intervention
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The presence of known or suspected brain metastases, including central nervous system and spinal cord compressions or meningeal metastases
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Subjects undergoing treatment with systemic steroids or steroid inhalers
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Subjects with any psychiatric disorder, including dementia, altered mental status, that may interfere with informed consent and understanding of relevant questionnaires
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Having participated in another clinical trial within the previous 30 days
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Have received a live or attenuated vaccine within 4 weeks prior to pretreatment
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Those who have been judged by the investigator to have a serious uncontrollable disease or have other conditions that may interfere with receiving treatment in this study and are considered unsuitable
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- su haichuan
Investigators
- Principal Investigator: Haichuan Su, Doctor, The Second Affiliated Hospital of PLA Air Force Medical University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- HER2-E-CART