Combination Immunotherapy Targeting Sarcomas

Sarcoma Clinical Trial

Official title:

Safety and Efficacy Evaluation of a Combination Immunotherapy Targeting Sarcomas

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04433221
• Other study ID #: GIMI-IRB-20007
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: July 1, 2020
• Est. completion date: December 31, 2023

Study information

• Verified date: June 2020
• Source: Shenzhen Geno-Immune Medical Institute
• Contact: Lung-Ji Chang, MD
• Phone: 86-(0755)86725195
• Email: c[@]szgimi.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The aim of this clinical trial is to assess the feasibility, safety and efficacy of a combination low dose chemotherapy and 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 multiple CAR T cells followed by sarcoma vaccines.

Description:

Patients with late staged and/or recurrent sarcoma have poor prognosis despite complex multimodal therapy. Therefore, innovative interventions are needed. Sarcoma is known to express increased levels of surface antigens that can be targeted by CAR-T cells. In addition, studies have shown that low dose chemotherapy such as doxorubicin may modulate surface PD-L1 level and enhance immunotherapy effects. This study will combine multiple CAR T cells with low dose chemotherapy to treat sarcoma, and followed by maintenance sarcoma vaccines. The purpose of this clinical trial will assess the feasibility, safety, efficacy and side effects of this combination therapy in patients who have sarcoma that is relapsed or late staged.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: December 31, 2023
• Est. primary completion date: May 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 75 Years

Eligibility

Inclusion Criteria:

1. Stage ?,? sarcoma patients or recurrent sarcoma patients;

2. Age: = 6 months and =80 years of age at the time of enrollment;

3. At least 2 weeks since the last standard chemotherapy or radiotherapy and immunosuppressive therapy such as steroid hormone before enrollment;

4. Side effects of chemotherapy have been well managed;

5. Confirmed malignant cell expression of CART target antigens by IHC or flow

6. Karnofsky /jansky score of 50% or greater;

7. Expected survival > 8 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 sufficient autologous CART cells at does greater than 0.5x10^6 cells/kg body weight;

13. Sign an informed consent and assent.

Exclusion Criteria:

1. The disease is progressing rapidly;

2. The patient is receiving therapy of other new drugs and under evaluation;

3. Evidence of tumor potentially causing airway obstruction;

4. Epilepsy history or other CNS diseases;

5. Patients who need immunosuppressive drugs;

6. History of long QT syndrome or severe heart diseases;

7. Uncontrolled active infection;

8. Active hepatitis B virus, hepatitis C virus or 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 such as obstruction of lung function would preclude participation as outlined;

13. Pregnant or lactating women;

14. Patients previously experienced toxicity from cyclophosphamide and doxorubicin;

15. Patients who have CNS sarcoma;

16. In condition that may bring risks to subjects or interference to clinical trials.

Related Conditions & MeSH terms

• Ewing Sarcoma
• Osteoid Sarcoma
• Sarcoma
• Sarcoma, Ewing

Intervention

Biological:
• Multiple sarcoma-specific CAR-T cells and sarcoma vaccines
1 infusion, CART 1x10^6~1x10^7 cells/kg via IV and vaccines 1-5x10^6 irradiated cells via subcutaneous injection

Locations

Country	Name	City	State
China	Shenzhen Children's Hospital	Shenzhen	Guangdong
China	The Seventh Affilliated Hospital, Sun Yat-Sen University	Shenzhen	Guangdong

Sponsors (3)

Lead Sponsor	Collaborator
Shenzhen Geno-Immune Medical Institute	Shenzhen Children's Hospital, The Seventh Affilliated Hospital, Sun Yat-Sen University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety of CART cells infusion	Safety of CART cells in patients using CTCAE version 4.0 standard to evaluate the level of adverse events	3 months
Secondary	Overall survival Rate	Percentage of participants with objective response as determined by the investigator based on Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1)	1 year
Secondary	Treatment response rate of sarcomas	Defined as the proportion of patients who achieved complete remission (CR), partial remission (PR), stable disease (SD), or progressive disease (PD) based on CT imaging analysis.	1 year