Her2 Chimeric Antigen Receptor Expressing T Cells in Advanced Sarcoma

Because the cells have a new gene in them the patient will be followed for a total of 15 years to see if there are any long term side effects of gene transfer.

When the patient is enrolled on this study, they will be assigned a dose of HER2-CD28 T cells. Depending on which dose level they are assigned, they will receive one of the following:

HER2-CD28 T cells and fludarabine (patient will receive fludarabine for 5 days followed by injection of HER2-CD28 T cells)

OR

HER2-CD28 T cells, fludarabine and cyclophosphamide (patient will receive fludarabine and cyclophosphamide for 2 days, fludarabine alone for an additional 3 days, and 2 days of rest before receiving the HER2-CD28 T cells.).

The HER2-CD28 T cells will be given 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.

Each patient will be followed for 6 weeks after the T-cell infusion for evaluation of toxicity. They will have standard tests and procedures as well as research blood draws.

If the patient has stable disease (the tumor did not grow) or there is a reduction in the size of the tumor on imaging studies after the T-cell infusion, they can receive additional doses of the T cells at 6 to 12 weeks intervals. For the first two subsequent HER2-specific T-cell infusions, patients will be able to receive additional lymphodepleting chemotherapy according to their dose levels.

Inclusion criteria

Procurement Eligibility:

• Diagnosis of refractory HER2-positive sarcoma or metastatic HER2-positive osteosarcoma.
• Karnofsky/Lansky score of 50 or greater
• Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent.

Treatment Eligibility:

• Diagnosis of refractory HER2-positive sarcoma or metastatic HER2-positive sarcoma with disease progression after receiving at least one prior systemic therapy.
• Recovered from acute toxic effects of all prior cytotoxic chemotherapy at least 4 weeks before entering this study. PD1/PDL1 inhibitors will be allowed to continue during treatment if medically indicated.
• Normal ECHO (Left ventricular ejection fraction (LVEF) has to be within normal, institutional limits)
• Life expectancy 6 weeks or greater
• Karnofsky/Lansky score of 50 or greater
• Bilirubin 3x or less, AST 3x or less, Serum creatinine 2x upper limit of normal or less, Hgb 7.0 g/dl or greater, WBC greater than 2,000/ul, ANC greater than 1,000/ul, platelets greater than 100,000/ul. Creatinine clearance is needed for patients with creatinine greater than 1.5 times upper limit of normal.
• Pulse oximetry of 90% or greater on room air
• 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
• Available autologous transduced T lymphocytes with 15% or more expression of HER2 CAR as determined by flow-cytometry and killing of HER2-positive targets 20 % or greater in cytotoxicity assay.
• Chest radiograph for baseline evaluation of lungs
• Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent

Exclusion criteria

At time of Procurement:

• Known HIV positivity
• Severe previous toxicity from cyclophosphamide or fludarabine

At time of Treatment:

• Severe intercurrent infection
• Known HIV positivity
• Pregnant or lactating
• History of hypersensitivity reactions to murine protein-containing products
• Severe previous toxicity from cyclophosphamide or fludarabine