Combination Immunotherapy Targeting Sarcomas

NCT ID: NCT04433221

Last Updated: 2020-06-16

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-07-01
• Study Completion Date: 2023-12-31

Brief 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.

Detailed 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.

Conditions

Sarcoma; Osteoid Sarcoma; Ewing Sarcoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Multiple sarcoma-specific CAR-T cells

Patients who have confirmed surface antigens including GD2, PSMA, Her2, CD276 or other markers

Group Type: EXPERIMENTAL

Multiple sarcoma-specific CAR-T cells and sarcoma vaccines

Intervention Type: BIOLOGICAL

1 infusion, CART 1x10\^6\~1x10\^7 cells/kg via IV and vaccines 1-5x10\^6 irradiated cells via subcutaneous injection

Interventions

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

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

1. Stage Ⅲ，Ⅳ 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.

• Minimum Eligible Age: 1 Year
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Seventh Affiliated Hospital of Sun Yat-sen University

OTHER

Sponsor Role: collaborator

Shenzhen Children's Hospital

OTHER_GOV

Sponsor Role: collaborator

Shenzhen Geno-Immune Medical Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Shenzhen Children's Hospital

Shenzhen, Guangdong, China

Site Status: RECRUITING

The Seventh Affilliated Hospital, Sun Yat-Sen University

Shenzhen, Guangdong, China

Site Status: RECRUITING

Countries

China

Central Contacts

Lung-Ji Chang, MD

Role: CONTACT

c@szgimi.org

86-(0755)86725195

Facility Contacts

Xiuli Yuan, MD

Role: primary

18938690212@163.com

86-18938690212

Bo Wang, MD

Role: primary

wangb68377@sina.com

86-0755-23242570

Other Identifiers

GIMI-IRB-20007

Identifier Type: -

Identifier Source: org_study_id