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CAR T and PD-1 Knockout Engineered T Cells for Esophageal Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03706326
Recruitment Status : Recruiting
First Posted : October 16, 2018
Last Update Posted : October 16, 2018
Sponsor:
Collaborator:
Guangzhou Anjie Biomedical Technology Co., Ltd.
Information provided by (Responsible Party):
Size Chen, The First Affiliated Hospital of Guangdong Pharmaceutical University

Brief Summary:
The study is to assess the safety and efficacy of the immunotherapies using anti-MUC1 CAR T cells and /or PD-1 knockout engineered T cells in the treatment of patients with advanced esophageal cancer.

Condition or disease Intervention/treatment Phase
Advanced Esophageal Cancer Biological: Anti-MUC1 CAR-T cells Biological: PD-1 knockout Engineered T cells Combination Product: CAR-T combined with PD-1 Knockout T cells Phase 1 Phase 2

Detailed Description:
This is a combined phase 1 and 2 clinical study. The aim of the study is to assess the safety and efficacy of the immunotherapies using anti- MUC1 CAR T cells alone, anti- MUC1 CAR T combining PD-1 knockout engineered T cells, and PD-1 knockout engineered T cell only in the treatment of patients with advanced esophageal cancer. The treatment outcomes from each group will be compared.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
Official Title: Combination Therapy of Anti-MUC1 CAR T Cells and PD-1 Knockout Engineered T Cells for Advanced Esophageal Cancer
Actual Study Start Date : September 28, 2018
Estimated Primary Completion Date : September 28, 2021
Estimated Study Completion Date : September 28, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Treatment with Anti-MUC1 CAR-T cells
Anti-MUC1 CAR-T cells will be prepared ex vivo using the T cells from the patients and infused back to the patients.
Biological: Anti-MUC1 CAR-T cells
Using the T cells from the patients' blood to produce anti-MUC1 CAR-T Cells and then the cells will be infused back to the patients.

Experimental: Combination Therapy: CAR-T combining PD-1 knockout T Cells
Anti-MUC1 CAR-T cells and PD-1 knockout Engineered T cells will be prepared ex vivo using the T cells from the patients and infused back to the patients.
Combination Product: CAR-T combined with PD-1 Knockout T cells
Using the T cells from the blood of the patients to prepare anti-MUC1 CAR-T Cells and PD-1 knockout T cells, then the cells will be infused back to the patients

Experimental: Treatment with PD-1 knockout Engineered T cells
PD-1 knockout Engineered T cells will be prepared ex vivo using the T cells from the patients and infused back to the patients.
Biological: PD-1 knockout Engineered T cells
Using the T cells from the blood of the patients to prepare PD-1 knockout T cells, then the cells will be infused back to the patients.




Primary Outcome Measures :
  1. Number of participants with adverse events and dose limiting toxicities as assessed by CTCAE v4.0 [ Time Frame: approximately 12 months ]
    Safety and tolerability of dose of CART-cells and PD-1 Knockout T cells will be assessed using CTCAE v4.0.


Secondary Outcome Measures :
  1. Response Rate [ Time Frame: 12 months ]
    Will be assessed according to the revised RECIST guideline v1.1

  2. Overall Survival - OS [ Time Frame: Up to 24 months ]
    Measure the time from enrollment to death

  3. Progression free survival - PFS [ Time Frame: Up to 12 months ]
    Time from enrollment to date of first documented progression or date of death.

  4. Median CAR-T cell persistence [ Time Frame: 3 years ]
    Will be measured by quantitative RT-PCR



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Confirmed diagnosis of advanced esophageal cancer (phase IIIb-IV) according to NCCN clinical practice guidelines in Oncology:Esophageal and Esophagogastric Junction Cancers (2018.V1).
  • MUC1 is highly expressed in malignancy tissues by immuno-histochemical (IHC).
  • Eastern cooperative oncology group (ECOG) performance status of 0-1 or karnofsky performance status (KPS) score is higher than 60.
  • Patients have a life expectancy > 12 weeks.
  • Adequate venous access for apheresis or venous sampling, and no other contraindications for leukapheresis.
  • Negative pregnancy test for females of child-bearing potentials.
  • Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements: White blood cell count (WBC) ≥ 2500c/ml, Platelets ≥ 50×10^9/L, Hb ≥ 9.0g/dL, lymphocyte (LY) ≥ 0.7×10^9/L, LY% ≥ 15%, Alb ≥ 2.8g/dL, serum lipase and amylase < 1.5×upper limit of normal, serum creatinine ≤ 2.5mg/dL, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 5×upper limit of normal, serum total bilirubin ≤ 2.0mg/dL. These tests must be conducted within 7 days prior to registration.
  • Signed informed consent form.

Exclusion Criteria:

  • Number of T cells is less than 10% or the amplification of the T cells via artificial antigen presenting cell (aAPC) stimulation is less than 5 times.
  • Patients with symptomatic central nervous system (CNS) involvement.
  • Pregnant or nursing women.
  • Known HIV, HBV and HCV infection.
  • Serious illness or medical condition which would not permit the patient to be managed according to the protocol, including active uncontrolled infection, major cardiovascular, coagulation disorders, respiratory or immune system, myocardial infarction, cardiac arrhythmias, obstructive/restrictive pulmonary disease, or psychiatric or emotional disorders.
  • History of severe immediate hypersensitivity to any of the agents including cyclophosphamide, fludarabine, or aldesleukin.
  • Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not exclusionary.
  • Previously treatment with any gene therapy products.
  • The existence of unstable or active ulcers or gastrointestinal bleeding. Patients with portal vein vascular invasion or extrahepatic, are excluded from this study.
  • Patients with a history of organ transplantation or are waiting for organ transplantation.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03706326


Contacts
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Contact: Size Chen, MD, PhD +8613720956393 13720956393@139.com
Contact: Zhizhou Huang, MSc +8613268258980 hzhizhou@sina.com

Locations
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China, Guangdong
First Affiliated Hospital of Guangdong Pharmaceutical University Recruiting
Guangzhou, Guangdong, China, 510080
Contact: Guobiao Huang    86-20-39352064    153706227@qq.com   
Professor Size Chen Recruiting
Guangzhou, Guangdong, China, 510080
Contact: Size Chen, MD,PhD    +8613720956393    13720956393@139.com   
Contact: Zhizhou Huang, MSc    +8613268258980    hzhizhou@sina.com   
Principal Investigator: Yiguang Lin, MD, PhD         
Principal Investigator: Size Chen, MD, PhD         
Sub-Investigator: Micheal Yin, PhD         
Sponsors and Collaborators
The First Affiliated Hospital of Guangdong Pharmaceutical University
Guangzhou Anjie Biomedical Technology Co., Ltd.
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Responsible Party: Size Chen, Associate Professor, The First Affiliated Hospital of Guangdong Pharmaceutical University
ClinicalTrials.gov Identifier: NCT03706326    
Other Study ID Numbers: 2018-6301
First Posted: October 16, 2018    Key Record Dates
Last Update Posted: October 16, 2018
Last Verified: October 2018

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Size Chen, The First Affiliated Hospital of Guangdong Pharmaceutical University:
Esophageal cancer
Neoplasms, Esophageal
Cancer of Esophagus
Solid tumor
Additional relevant MeSH terms:
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Esophageal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Head and Neck Neoplasms
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases