CAR T and PD-1 Knockout Engineered T Cells for Esophageal Cancer
Combination Therapy of Anti-MUC1 CAR T Cells and PD-1 Knockout Engineered T Cells for Advanced Esophageal Cancer
1 other identifier
interventional
20
1 country
2
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started Sep 2018
Typical duration for phase_1
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
September 28, 2018
CompletedFirst Submitted
Initial submission to the registry
October 11, 2018
CompletedFirst Posted
Study publicly available on registry
October 16, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 28, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
September 28, 2021
CompletedOctober 16, 2018
October 1, 2018
3 years
October 11, 2018
October 11, 2018
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Number of participants with adverse events and dose limiting toxicities as assessed by CTCAE v4.0
Safety and tolerability of dose of CART-cells and PD-1 Knockout T cells will be assessed using CTCAE v4.0.
approximately 12 months
Secondary Outcomes (4)
Response Rate
12 months
Overall Survival - OS
Up to 24 months
Progression free survival - PFS
Up to 12 months
Median CAR-T cell persistence
3 years
Study Arms (3)
Treatment with Anti-MUC1 CAR-T cells
EXPERIMENTALAnti-MUC1 CAR-T cells will be prepared ex vivo using the T cells from the patients and infused back to the patients.
Combination Therapy: CAR-T combining PD-1 knockout T Cells
EXPERIMENTALAnti-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.
Treatment with PD-1 knockout Engineered T cells
EXPERIMENTALPD-1 knockout Engineered T cells will be prepared ex vivo using the T cells from the patients and infused back to the patients.
Interventions
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.
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.
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
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (2)
First Affiliated Hospital of Guangdong Pharmaceutical University
Guangzhou, Guangdong, 510080, China
Professor Size Chen
Guangzhou, Guangdong, 510080, China
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- SINGLE
- Who Masked
- PARTICIPANT
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Associate Professor
Study Record Dates
First Submitted
October 11, 2018
First Posted
October 16, 2018
Study Start
September 28, 2018
Primary Completion
September 28, 2021
Study Completion
September 28, 2021
Last Updated
October 16, 2018
Record last verified: 2018-10