HER2 Positive Malignancies Clinical Trial
— HERCREEMOfficial title:
Administration of Her2 Chimeric Receptor and TGFbeta Dominant Negative Receptor (DNR) Expressing EBV Specific Lymphocytes for Subjects With Advanced Her2 Positive Malignancy (HERCREEM)
| Verified date | September 2018 |
| Source | Baylor College of Medicine |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
Patients have advanced stage cancer. This study is a gene transfer research study using
special immune cells.
The body has different ways of fighting infection and disease. No single way seems perfect
for fighting cancers. This research study combines two different ways of fighting cancer:
antibodies and T cells. Investigators hope that both will work better together. Antibodies
are proteins that protect the body from diseases caused from infectious diseases and possibly
cancer. T cells, also called T lymphocytes, are special infection-fighting blood cells that
can kill other cells, including tumor cells or cells that are infected with germs. Both
antibodies and T cells have been used to treat patients with cancers: they both have shown
promise, but have not been strong enough to cure most patients.
T lymphocytes can kill tumor cells but there are normally not enough of them or they are not
able to kill all the tumor cells. We have done research in which we have grown "extra" T
lymphocytes. We have added genes to those T lymphocytes to help them to recognize tumor
cells. Although the results have been promising, we are still doing more research in this
area.
Antibodies usually circulate in blood and are secreted by other cells of the immune system in
response to the presence of germs or abnormal cells in the body. The antibody used in this
study is called anti-HER2 (Human Epidermal Growth Factor Receptor 2). This antibody sticks to
HER2-positive cancer cells because of a substance on the outside of these cells called HER2.
| Status | Completed |
| Enrollment | 20 |
| Est. completion date | January 21, 2018 |
| Est. primary completion date | July 2015 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 3 Years and older |
| 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 |
| Country | Name | City | State |
|---|---|---|---|
| United States | Houston Methodist Hospital | Houston | Texas |
| United States | Texas Children's Hospital | Houston | Texas |
| Lead Sponsor | Collaborator |
|---|---|
| Baylor College of Medicine | Center for Cell and Gene Therapy, Baylor College of Medicine, The Methodist Hospital System |
United States,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Number of Patients with dose limiting toxicity. | Determine safety of one IV injection of autologous TGFBeta-resistant cytotoxic T cells (CTL) directed to Epstein Barr virus (EBV) through their native receptor and HER2 through their chimeric antigen receptor (CAR) in patients with advanced HER2- positive cancers. | 6 weeks | |
| Secondary | Area under the growth curves (AUC) over time for T cell frequencies. | To compare the survival and the immune function of the TGFBeta-resistant and non resistant components of the infused CAR-CTL. | 15 years | |
| Secondary | Decrease in tumor after the CTL infusion | To assess the anti-tumor effects of the infused CAR-CTL. | 15 years |