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This gene transfer study combines two ways of fighting cancer, antibodies and T cells, in patients with advanced cancer. The patient's own T cells are modified in the laboratory to recognize HER2 and to resist the suppressive effect of TGF-beta (HER2-DNR EBV T cells), then given back to the patient. The Phase 1 trial enrolled patients with confirmed advanced-stage or metastatic HER2-positive cancer.
The summary above is a plain-language rendering of the official record. The original English title is shown for reference.
Criteria are reproduced from the ClinicalTrials.gov record in the original English. Only the trial team can determine eligibility.
INCLUSION CRITERIA:
The patient must meet the following eligibility inclusion criteria at the time of PROCUREMENT:
1. Diagnosis of advanced stage\* or metastatic HER2-positive cancer (Immunohistochemistry or reverse transcription-polymerase chain reaction (RT-PCR) is used to determine HER2 positivity)
Definitions of Malignancies and Advanced Stages:
Breast ≥Stage IIIb Colon cancer ≥Stage IIIb Esophageal cancer ≥Stage IIIb Gastric carcinoma ≥Stage IIIb Head and Neck cancer Stage IV Lung cancer ≥Stage IIIb Pancreatic cancer Stage IV Prostate cancer Stage IV
\*it is expected that the majority of patients who will be accrued on the protocol will have one of the HER2-positive malignancies listed in the table. If the patient's malignancy is not listed we will use ≥ Stage IIIb as the definition of advanced stage disease. If Stage IIIb is not part of the staging system for the individual tumor, Stage IV will be used.
For World Health Organization grade III and IV brain tumors):patients will be eligible, who have recurrent or progressive disease after front line therapy.
2. Karnofsky/Lansky score of 50 or more
3. EBV seropositive
4. Greater than or equal to 3 years old
5. Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent.
The patient must meet the following eligibility criteria to be included for TREATMENT:
1. Diagnosis of advanced stage\* or metastatic HER2-positive cancer with disease progressed after receiving at least one prior systemic therapy. (Immunohistochemistry or RT-PCR is used to determine HER2 positivity) \*for definition refer to Table above.
2. Greater than or equal to 3 years old.
3. EBV-seropositive
4. Recovered from the acute toxic effects of all prior chemotherapy at least a week before entering this study.
5. Normal echocardiogram (Left ventricular ejection fraction (LVEF) has to be with in normal, institutional limits)
5\. Life expectancy 6 weeks or more
7\. Karnofsky/Lansky score of 50 or more
8\. Bilirubin 3x or less, Aspartate aminotransferase (AST) 5x or less, Serum creatinine 2x or less upper limit of normal, Hgb 9.0 g/dl or more, white blood cells greater than 2,000/ul, absolute neutrophil count greater than 1,000/ul, Platelets greater than 100,000/ul
9\. Pulse oximetry 90% or more on room air
10\. Sexually active patients must be willing to utilize one of the more effective birth control methods for 6 months after the CTL infusion. Male partner should use a condom. Acceptable forms of birth control include: \* oral contraceptives ("the pill"), \* intrauterine devices (IUDs), \* contraceptive implants under the skin, or contraceptive injections, \* condoms with foam.
11\. Available autologous transduced EBV-specific cytotoxic T lymphocytes with 15% or more expression of HER2 CAR determined by flow-cytometry and killing of Her2-positive targets 20% or more in cytotoxicity assay.
12\. Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent
Note: Patients must also not receive antineoplastic drugs while on this study since they would kill the infused T cells.
EXCLUSION CRITERIA:
At time of Procurement:
1\. Known HIV positivity
At time of Treatment:
1. Severe intercurrent infection
2. Known HIV positivity
3. Pregnant or lactating
4. History of hypersensitivity reactions to murine protein-containing products