Combination Immunotherapy Targeting Sarcomas

• ClinicalTrials.gov Identifier: NCT04433221
• Recruitment Status: Unknown
• First Posted: June 16, 2020
• Last Update Posted: June 16, 2020
• Sponsor: Shenzhen Geno-Immune Medical Institute
• Collaborators: The Seventh Affiliated Hospital of Sun Yat-sen University; Shenzhen Children's Hospital
• Information provided by (Responsible Party): Shenzhen Geno-Immune Medical Institute

Tracking Information

• First Submitted Date: June 9, 2020
• First Posted Date: June 16, 2020
• Last Update Posted Date: June 16, 2020
• Estimated Study Start Date: July 1, 2020
• Estimated Primary Completion Date: May 31, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 12, 2020)

Safety of CART cells infusion [ Time Frame: 3 months ]

Safety of CART cells in patients using CTCAE version 4.0 standard to evaluate the level of adverse events

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: June 12, 2020)

• Overall survival Rate [ Time Frame: 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)
• Treatment response rate of sarcomas [ Time Frame: 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.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Combination Immunotherapy Targeting Sarcomas
• Official Title: Safety and Efficacy Evaluation of a Combination Immunotherapy Targeting Sarcomas
• 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 Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Sarcoma
• Osteoid Sarcoma
• Ewing Sarcoma

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

Study Arms

Experimental: Multiple sarcoma-specific CAR-T cells

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

Intervention: Biological: Multiple sarcoma-specific CAR-T cells and sarcoma vaccines

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: June 12, 2020): 20
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 31, 2023
• Estimated Primary Completion Date: May 31, 2023 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 1 Year to 75 Years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT04433221
• Other Study ID Numbers: GIMI-IRB-20007
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Shenzhen Geno-Immune Medical Institute
• Original Responsible Party: Same as current
• Current Study Sponsor: Shenzhen Geno-Immune Medical Institute
• Original Study Sponsor: Same as current

Collaborators

• The Seventh Affiliated Hospital of Sun Yat-sen University
• Shenzhen Children's Hospital

• Investigators: Not Provided
• PRS Account: Shenzhen Geno-Immune Medical Institute
• Verification Date: June 2020