Allogenic Immunotherapy Based on Natural Killer (NK) Cell Adoptive Transfer in Metastatic Gastrointestinal Carcinoma Treated With Cetuximab (NK-EGFR01)
Gastrointestinal Metastatic Cancer
About this trial
This is an interventional treatment trial for Gastrointestinal Metastatic Cancer focused on measuring natural killer cells, adoptive transfer, allogenic immunotherapy, gastrointestinal cancer EGFR+
Eligibility Criteria
Inclusion Criteria:
- metastatic gastrointestinal cancer (colorectal, pancreas, small intestine, bile ducts), gastrointestinal stromal tumor or digestive neuroendocrine tumor.
- presence of liver metastases
- Age > 18 and < 65 (male and female)
- ECOG performances status 0 or 1
- EGFR expression confirmed by immunohistochemistry
- allogenic donor with one or more KIR/MHC class I mismatch
- absence of alternative treatment available
- evidence of progressive disease
- written informed consent
Exclusion Criteria:
- malignant secondary disease dated backed < 2 years (exception : in situ carcinoma of the cervix uteri, adequately treated skin basal cell carcinoma)
- hypersensitivity against one of the treatment of this study
- history of cardiac or respiratory failure
- history of auto-immune disease
- renal or hepatic failure
- pregnancy or lactation
- patient with any medical or psychiatric condition or disease which would makes the patient inappropriate for entry into this study.
- EBV serology negative in recipient and positive in donor
- bilirubin greater than 1,5 times upper limit of normal
- ASAT and/or alkaline phosphatase greater than 5 times upper limit of normal in presence of liver metastases.
Sites / Locations
- University hospital of Besançon
Arms of the Study
Arm 1
Experimental
Allogenic NK cells transfer
Patients will be treated with a conditioning chemotherapy including 60 mg/kg intravenous cyclophosphamide, 25 mg/m2 intravenous fludarabine for 5 consecutive days and cetuximab. A lymphapheresis from an haploidentical related donor will be performed and T cells will be depleted . Allogenic NK cells will then be adoptively transferred by hepatic intraarterial infusion according to a dose escalation protocol (three doses with at least three patients per cohort)to define the dose-limiting toxicity (DLT). T