Chimeric Switch Receptor Modified T Cells for Patients With PD-L1+ Recurrent or Metastatic Malignant Tumors

NCT02930967 | Unknown Phase 1

• 1 other identifier: K16-3
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

A Chimeric Switch Receptor, which was constructed by fusing the PD1 extracellular ligand binding domain to the CD28 intracellular costimulatory domain, was designed to target PD-L 1 positive tumors . In this single-arm, open-label, one center, dose escalation clinical study, the main purpose is to determine the safety and efficacy of infusion of autologous Chimeric Switch Receptor modified T cells (CSR T) in adult patients with PD-L1 positive, recurrent or metastatic malignant tumors.

Conditions

Recurrent PD-L1+ Malignant Tumors; Metastatic PD-L1+ Malignant Tumors

Outcome Measures

Primary Outcomes (1)

• Safety as assessed by incidents of treatment related adverse events as assessed by CTCAE V4.0.

  safety of infusion of autologous CSR T cells with cyclophosphamide as lymphodepleting chemotherapy

  2 years

Secondary Outcomes (5)

• treatment response rate of CSR T cell infusion

  4 weeks

• overall survival rate

  2 years

• progression-free survival

  6 months

• proliferation of CSR T cells in patients

  2 years

• Persistence of CSR T cells in patients

  2 years

Study Arms (1)

CSR T cells

EXPERIMENTAL

A dose escalation clinical study aimed to assess the safety and efficacy of CSR T cells in patients with PD-L1 positive tumors. CSR T dosage ranging from: 5×10\^4 /kg to 1×10\^7 /kg will be tested.

Biological: autologous CSR T

Interventions

autologous CSR T BIOLOGICAL

Patients will be received a three-day regimen of chemotherapy consisting of cyclophosphamide aimed to deplete the lymphocytes. 1 to 4 days after lymphodepletion, a prescribed dose of CSR T cells will be intravenously infused to patient in a three-day split-dose regimen (day0,10%; day1, 30%; day2, 60%).

CSR T cells

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with PD-L1 positive, recurrent or metastatic malignant tumors , including but not limited to pancreatic cancer, renal cancer, colorectal cancer, lymphoma, breast cancer and lung cancer;
• measurable tumors by RECIST1.1 standard;
• patients are 18 to 70 years old;
• life expectancy \> 3months;
• KPS ≥70;
• satisfactory major organ functions: adequate heart function with LVEF≥50%; no obvious abnormities in ECG; pulse oximetry ≥ 90%; cockcroft-gault creatinine clearance≥40 ml/min; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3ULN; Bilirubin ≤2.0 mg/dl ;
• Blood: Hgb ≥ 80 g/L, ANC ≥ 1×10\^9/L, PLT ≥ 50×10\^9/L;
• women of reproductive potential must have a negative pregnancy test. Male and female of reproductive potential must agree to use birth control during the study and one year post study.

You may not qualify if:

• patients with a prior history of autoimmune disease or other diseases who need long-term use of systemic hormone drug or immunosuppressive therapy
• active infection.
• HIV positive.
• active hepatitis B virus infection or hepatitis C virus infection.
• currently enrolled in other study.
• patients, in the opinion of investigators, may not be eligible or are not able to comply with the study.
• patients with allergic disease, or are allergic to T cell products or other biological agents used in the study.
• patients whose tumors have metastasized to bone, or have clinical signs of bone metastasis, such as bone and joint pain.
• patients with brain metastasis, or have clinical signs of brain metastasis, such as loss of self-consciousness.

Sponsors & Collaborators

• China Meitan General Hospital: lead
• Marino Biotechnology Co., Ltd.: collaborator

Study Sites (1)

China Meitan General Hospital

Beijing, 100028, China

RECRUITING

Study Officials

• Jinwen Sun, MD

  China Meitan General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Shidong Wei, MD

CONTACT

+86-13146634751; liqinghe9644679@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Department of General Surgery and Surgical Oncology

Study Record Dates

• First Submitted: October 10, 2016
• First Posted: October 12, 2016
• Study Start: August 1, 2016
• Primary Completion: August 1, 2018
• Study Completion: August 1, 2019
• Last Updated: October 12, 2016

Record last verified: 2016-10

Locations

CN (1)