Clinical trial NCT03706326: CAR T and PD-1 Knockout Engineered T Cells for Esophageal Cancer
Official title: Combination Therapy of Anti-MUC1 CAR T Cells and PD-1 Knockout Engineered T Cells for Advanced Esophageal Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Advanced Esophageal Cancer
Keywords: Esophageal cancer
Neoplasms, Esophageal
Cancer of Esophagus
Solid tumor
Lead sponsor: The First Affiliated Hospital of Guangdong Pharmaceutical University
Sponsor class: OTHER
Collaborators: name: Guangzhou Anjie Biomedical Technology Co., Ltd.
First posted: 2018-10-16
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility 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.

Primary outcomes:
measure: Number of participants with adverse events and dose limiting toxicities as assessed by CTCAE v4.0
timeFrame: approximately 12 months
Secondary outcomes:
measure: Response Rate
timeFrame: 12 months
measure: Overall Survival - OS
timeFrame: Up to 24 months
measure: Progression free survival - PFS
timeFrame: Up to 12 months
measure: Median CAR-T cell persistence
timeFrame: 3 years
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: First Affiliated Hospital of Guangdong Pharmaceutical University
state: Guangdong
city: Guangzhou
country: China
facility: Professor Size Chen
state: Guangdong
Study officials:
References: