Combination Immunotherapy Targeting Sarcomas

Safety and Efficacy Evaluation of a Combination Immunotherapy Targeting Sarcomas

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.

Study Overview

• Status: Recruiting
• Conditions: Sarcoma; Ewing Sarcoma; Osteoid Sarcoma
• Intervention / Treatment: Biological: Multiple sarcoma-specific CAR-T cells and 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 Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Lung-Ji Chang, MD; Phone Number: 86-(0755)86725195; Email: c@szgimi.org

Study Locations

• China
  • Guangdong
    • Shenzhen, Guangdong, China, 518000
      • Recruiting
      • Shenzhen Children's Hospital
      • Contact: Xiuli Yuan, MD; Phone Number: 86-18938690212; Email: 18938690212@163.com
    • Shenzhen, Guangdong, China, 518107
      • Recruiting
      • The Seventh Affilliated Hospital, Sun Yat-Sen University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 months to 73 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Multiple sarcoma-specific CAR-T cells; Patients who have confirmed surface antigens including GD2, PSMA, Her2, CD276 or other markers	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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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

Collaborators and Investigators

• Sponsor: Shenzhen Geno-Immune Medical Institute
• Collaborators: The Seventh Affiliated Hospital of Sun Yat-sen University; Shenzhen Children's Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): July 1, 2020
• Primary Completion (Anticipated): May 31, 2023
• Study Completion (Anticipated): December 31, 2023

Study Registration Dates

• First Submitted: June 9, 2020
• First Submitted That Met QC Criteria: June 12, 2020
• First Posted (Actual): June 16, 2020

Study Record Updates

• Last Update Posted (Actual): June 16, 2020
• Last Update Submitted That Met QC Criteria: June 12, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: Vaccine; Chemotherapy; Doxorubicin; Sarcoma; CART
• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Osteosarcoma; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Sarcoma; Sarcoma, Ewing
• Other Study ID Numbers: GIMI-IRB-20007

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No