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Administration of Her2 Chimeric Receptor and TGFbeta Dominant Negative Receptor (DNR) Expressing EBV Specific Lymphocytes for Subjects With Advanced Her2 Positive Malignancy (HERCREEM)


Phase 1
3 Years
N/A
Open (Enrolling)
Both
HER2 Positive Malignancies

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Trial Information

Administration of Her2 Chimeric Receptor and TGFbeta Dominant Negative Receptor (DNR) Expressing EBV Specific Lymphocytes for Subjects With Advanced Her2 Positive Malignancy (HERCREEM)


The patient will give blood to grow T cells on either one to two separate occasions. Then,
the EBV-specific T cells will be made. These cells will be grown and frozen. To get the HER2
antibody (and the CD28) and the DNR to attach to the surface of the EBV-T cells, the
antibody gene and the DNR gene will be inserted into the EBV-T cell. This is done with two
viruses called retroviruses that have been made for this study. One will carry the antibody
gene into the T cell and the other the DNR gene.

When the patient is enrolled on the study, they will be assigned to a dose of HER2-DNR EBV-T
cells. The subject will be given one dose of cells into the vein through an IV line. The
injection will take between 1 and 10 minutes. The patient will be followed in the clinic
after the injection for 1 to 4 hours. The treatment will be given by the Center for Cell and
Gene Therapy at Texas Children's Hospital or The Methodist Hospital.

Inclusion Criteria


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 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 GBM (Glioblastoma, WHO grade IV):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 ECHO (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, AST 5x or less, Serum creatinine 2x upper limit of normal or
less, Hgb 9.0 g/dl or more, WBC greater than 2,000/ul, ANC 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

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Determine safety of one IV injection of autologous TGFBeta-resistant CTLs 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.

Outcome Time Frame:

6 weeks

Safety Issue:

Yes

Principal Investigator

Stepehen Gottschalk, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Baylor College of Medicine/Texas Children's Hospital

Authority:

United States: Institutional Review Board

Study ID:

24486-HERCREEM

NCT ID:

NCT00889954

Start Date:

May 2009

Completion Date:

July 2030

Related Keywords:

  • HER2 Positive Malignancies
  • EBV+
  • Her2
  • TGFBeta
  • EBV positive
  • HER 2 positive malignancy
  • cytotoxic T lymphocytes
  • Neoplasms

Name

Location

Texas Children's HospitalHouston, Texas  
The Methodist HospitalHouston, Texas  77030