Combination Immunotherapy Targeting Sarcomas

Phase 1

• Conditions: Sarcoma; Ewing Sarcoma; Osteoid Sarcoma
• Interventions: Biological: Multiple sarcoma-specific CAR-T cells and sarcoma vaccines

• Registration Number: NCT04433221
• Lead Sponsor: Shenzhen Geno-Immune Medical Institute

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.

Study Timeline

• Status Verified: 2020-06
• Study First Submitted: 2020-06-09
• Study First Submitted QC: 2020-06-12
• Last Update Submitted: 2020-06-12
• Study First Posted: 2020-06-16
• Last Update Posted: 2020-06-16
• Study Start: 2020-07-01
• Primary Completion: 2023-05-31
• Study Completion: 2023-12-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 20

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Multiple sarcoma-specific CAR-T cells	Multiple sarcoma-specific CAR-T cells and sarcoma vaccines	Patients who have confirmed surface antigens including GD2, PSMA, Her2, CD276 or other markers

Primary Outcome Measures

Name	Time	Method
Safety of CART cells infusion	3 months	Safety of CART cells in patients using CTCAE version 4.0 standard to evaluate the level of adverse events

Secondary Outcome Measures

Name	Time	Method
Treatment response rate of sarcomas	1 year	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.
Overall survival Rate	1 year	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)

Trial Locations

Locations (2)

Shenzhen Children's Hospital; 🇨🇳 Shenzhen, Guangdong, China

The Seventh Affilliated Hospital, Sun Yat-Sen University; 🇨🇳 Shenzhen, Guangdong, China