Safety and Efficacy Evaluation of 4th Generation Safety-engineered CAR T Cells Targeting Sarcomas
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Important Regulatory Notice:
This trial record is only for global academic information registration on ClinicalTrials.gov. Neither the sponsor Beijing Meikang Jimian Biotechnology Co., Ltd. nor collaborator Shenzhen Geno-Immune Medical Institute has obtained NMPA clinical trial approval or clinical technology filing permission to carry out interventional cell therapy trials in mainland China.
ClinicalTrials.gov registration alone does not represent legal approval by Chinese health and drug regulatory authorities.
Patients with late staged and/or recurrent sarcoma have poor prognosis despite complex multimodal therapy. Therefore, novel curative approaches are needed.This study will combine two different ways to fight sarcoma: antibodies and CAR-T cells. Several immune checkpoint antibodies have been examined on various tumors with good outcomes. Sarcoma is known to express increased levels of surface antigens that can be targeted by CAR-T cells. Thus, in this study, the 4SCAR-IgT cells targeting sarcoma surface antigens will be infused in dose escalation cohorts.This study will assess the feasibility, safety, efficacy and side effects of CAR T cells immunotherapy in patients who have sarcoma that is relapsed or late staged.
Study Type
Enrollment (Estimated)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Contact
- Name: Lung-Ji Chang, PhD
- Phone Number: +86 0755-86573763
- Email: c@szgimi.org
Study Locations
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Guangdong
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Shenzhen, Guangdong, China, 518000
- Shenzhen Geno-immune Medical Institute
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Contact:
- Lung-Ji Chang, PhD
- Phone Number: +86 0755-86573763
- Email: c@szgimi.org
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Stage Ⅲ，Ⅳ sarcoma patients or recurrent sarcoma patients;
- Age: ≥ 18 and ≤65 years of age at the time of enrollment;
- At least 4 weeks since any chemotherapy or radiotherapy and at least 1 week since immunosuppressive therapy such as using steroid hormone before enrollment;
- Side effects of chemotherapy have been well managed;
- Malignant cells are target antigen positive(higher than ++) confirmed by IHC, quantitative PCR or sequencing;
- Karnofsky /jansky score of 50% or greater;
- Expected survival > 6 weeks;
- ANC≥ 1×10^6/L，PLT ≥ 1×10^8/L;
- Pulse oximetry of≥90% on room air；
- Adequate hepatic function,defined as aspartate aminotransferase(AST)< 5 times upper limit of normal(ULN),serum bilirubin < 3 times ULN;
- Adequate renal function,defined as serum creatinine less than 2 times ULN,if serum creatinine more than 1.5 times ULN,creatinine clearance rate test is needed;
- Patients must have autologous transduced T cells at levels greater than 15%;
- Sign an informed consent and assent.
Exclusion Criteria:
- The disease is progresseing rapidly;
- The patient is receiving therapy of other new drugs;
- Evidence of tumor potentially causing airway obstruction;
- Epilepsy history or other CNS diseases;
- Patients who need immunosuppressive drugs because of GVAD;
- History of long QT syndrome or severe heart diseases;
- Uncontrolled active infection;
- Active hepatitis B virus,hepatitis C virus and HIV infection;
- Receiving systemic corticosteroid 2 weeks before enrollment except for inhaled steroids;
- Previous treatment with any gene therapy;
- Creatinine>2.5mg/dl or ALT/AST>3 times normal or bilirubin>2.0 mg/dl;
- Patients who have other uncontrolled diseases would preclude participation as outlined;
- Pregnant or lactating women;
- Patients previously experienced toxicity from cyclophosphamide;
- Patients who have CNS sarcoma;
- In condition that may bring risks to subjects or interference to clinical trials.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Experimental: Sarcoma-specific CAR-T cells
Peripheral blood mononuclear cells (PBMCs) of patients who have CD133, GD2, Muc1, CD117 or other marker positive sarcoma will be obtained through apheresis, and T cells will be activated and modified to sarcoma-specific CAR-T cells.
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1 infusion, for 1x10^6~1x10^7 cells/kg via IV
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Safety of CART cells in patients using CTCAE version 4.0 standard to evaluate the level of adverse events
Time Frame: 3 months
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Physiological parameter (measuring cytokine response)
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3 months
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
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Persistence and proliferation of CART cells in patients
Time Frame: 3 months
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The expansion and functional persistence of CART cells in the peripheral blood of patients will be measured by qPCR on Day 7, 14, 21, 28, 60 and 90 after infusion.
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3 months
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Anti-tumor effects
Time Frame: 1 year
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Objective response, such as complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD) will be assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria.
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1 year
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Collaborators and Investigators
Investigators
- Principal Investigator: Lung-Ji Chang, PhD, Shenzhen Geno-immune Medical Institute
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Estimated)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- GIMI-IRB-17016
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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