Clinical trial NCT03356782: Safety and Efficacy Evaluation of 4th Generation Safety-engineered CAR T Cells Targeting Sarcomas
Official title: Safety and Efficacy Evaluation of 4th Generation Safety-engineered CAR T Cells Targeting Sarcomas
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Sarcoma
Osteoid Sarcoma
Ewing Sarcoma
Keywords: CART
PD-1
PDL-1
CTLA-4
sarcoma
solid tumor
Lead sponsor: Shenzhen Geno-Immune Medical Institute
Sponsor class: OTHER
First posted: 2017-11-29
Enrollment: 20
Sex: ALL
Minimum age (years): 1
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The aim of this clinical trial is to assess the feasibility, safety and efficacy of CAR T cells immunotherapy in patients who have sarcoma that is relapsed or late staged. Another goal of the study is to assess the safety and efficacy of the therapy that combines CAR T cells and IgT cells to treat sarcoma.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

1. Stage Ⅲ，Ⅳ sarcoma patients or recurrent sarcoma patients;
2. Age: ≥ 18 and ≤65 years of age at the time of enrollment;
3. At least 4 weeks since any chemotherapy or radiotherapy and at least 1 week since immunosuppressive therapy such as using steroid hormone before enrollment;
4. Side effects of chemotherapy have been well managed;
5. Malignant cells are target antigen positive(higher than ++) confirmed by IHC, quantitative PCR or sequencing;
6. Karnofsky /jansky score of 50% or greater;
7. Expected survival \> 6 weeks;
8. ANC≥ 1×10\^6/L，PLT ≥ 1×10\^8/L;
9. Pulse oximetry of≥90% on room air；
10. Adequate hepatic function,defined as aspartate aminotransferase(AST)\< 5 times upper limit of normal(ULN),serum bilirubin \< 3 times ULN;
11. 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;
12. Patients must have autologous transduced T cells at levels greater than 15%;
13. Sign an informed consent and assent.

Exclusion Criteria:

1. The disease is progresseing rapidly;
2. The patient is receiving therapy of other new drugs;
3. Evidence of tumor potentially causing airway obstruction;
4. Epilepsy history or other CNS diseases;
5. Patients who need immunosuppressive drugs because of GVAD;
6. History of long QT syndrome or severe heart diseases;
7. Uncontrolled active infection;
8. Active hepatitis B virus,hepatitis C virus and HIV infection;
9. Receiving systemic corticosteroid 2 weeks before enrollment except for inhaled steroids;
10. Previous treatment with any gene therapy;
11. Creatinine\>2.5mg/dl or ALT/AST\>3 times normal or bilirubin\>2.0 mg/dl;
12. Patients who have other uncontrolled diseases would preclude participation as outlined;
13. Pregnant or lactating women;
14. Patients previously experienced toxicity from cyclophosphamide;
15. Patients who have CNS sarcoma;
16. In condition that may bring risks to subjects or interference to clinical trials.

Primary outcomes:
measure: Safety of CART cells in patients using CTCAE version 4.0 standard to evaluate the level of adverse events
timeFrame: 3 months
Secondary outcomes:
measure: Persistence and proliferation of CART cells in patients
timeFrame: 3 months
Other outcomes:
measure: Anti-tumor effects
timeFrame: 1 year
Locations:
city: Shenzhen
country: China
facility: Shenzhen Geno-immune Medical Institute
state: Guangdong
Study officials:
affiliation: Shenzhen Geno-Immune Medical Institute
name: Lung-Ji Chang, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hattinger CM, Patrizio MP, Magagnoli F, Luppi S, Serra M. An update on emerging drugs in osteosarcoma: towards tailored therapies? Expert Opin Emerg Drugs. 2019 Sep;24(3):153-171. doi: 10.1080/14728214.2019.1654455. Epub 2019 Aug 14.