MAGE-A3/12 Metastatic Cancer Treatment With Anti-MAGE-A3/12 TCR-Gene Engineered Lymphocytes

This is an interventional treatment trial for Metastatic Cancer focused on measuring Immunotherapy, Gene Therapy, Metastatic Cancer, Clinical Response, Metastatic Melanoma, Metastatic Renal Cell Cancer Read More

• INCLUSION CRITERIA:

Metastatic cancer that expresses MAGE-A3/12 as assessed by one of the following methods: reverse transcription polymerase chain reaction (RT-PCR) on tumor tissue defined as 30,000 copies of MAGE-A3/12 per 106 GAPDH copies, or by immunohistochemistry of resected tissue defined as 10% or greater of cells being 2-3+, or serum antibody reactive with MAGE-A3/12. Metastatic cancer diagnosis will be confirmed by the Laboratory of Pathology at the National Cancer Institute (NCI).

Patients with melanoma or renal cell cancer must have previously received high dose aldesleukin and have been either non-responders (progressive disease) or have recurred. Patients with other histologies, must have previously received at least one systemic standard care (or effective salvage chemotherapy regimens) for metastatic disease, if known to be effective for that disease, and have been either non-responders (progressive disease) or have recurred.

Greater than or equal to 18 years of age.

Willing to sign a durable power of attorney

Able to understand and sign the Informed Consent Document

Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0 or 1.

Life expectancy of greater than three months.

Patients of both genders must be willing to practice birth control for four months after receiving the preparative regimen.

Patients must be human leukocyte antigen (HLA)-A*0201 positive

Serology:

• Seronegative for human immunodeficiency virus (HIV) antibody. (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who are HIV seropositive can have decreased immune -competence and thus be less responsive to the experimental treatment and more susceptible to its toxicities.)
• Seronegative for hepatitis B antigen and hepatitis C antibody unless antigen negative.

Hematology:

• Absolute neutrophil count greater than 1000/mm^3 without the support of filgrastim.
• White blood cell (WBC) (> 3000/mm^3).
• Platelet count greater than 100,000/mm^3.
• Hemoglobin greater than 8.0 g/dl.

Chemistry:

• Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) less or equal to 2.5 times the upper limit of normal.
• Serum creatinine less than or equal to 1.6 mg/dl.
• Total bilirubin less than or equal to 1.5 mg/dl, except in patients with Gilbert's Syndrome who must have a total bilirubin less than 3.0 mg/dl.

More than four weeks must have elapsed since any prior systemic therapy at the time the patient receives the preparative regimen, and patients' toxicities must have recovered to a grade 1 or less (except for toxicities such as alopecia or vitiligo).

EXCLUSION CRITERIA:

Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant.

Active systemic infections, coagulation disorders or other major medical illnesses of the cardiovascular, respiratory or immune system, myocardial infarction, cardiac arrhythmias, obstructive or restrictive pulmonary disease.

Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease).

Concurrent opportunistic infections (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who have decreased immune competence may be less responsive to the experimental treatment and more susceptible to its toxicities).

Concurrent Systemic steroid therapy

History of severe immediate hypersensitivity reaction to any of the agents used in this study.

History of coronary revascularization or ischemic symptoms

Any patient known to have an left ventricular ejection fraction (LVEF) less than or equal to 45%.

Documented LVEF of less than or equal to 45% tested in patients with:

• History of ischemic heart disease, chest pain, or clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block
• Age greater than or equal to 60 years old

Documented forced expiratory volume 1 (FEV1) less than or equal to 60% predicted tested in patients with:

• A prolonged history of cigarette smoking (20 pk/year of smoking within the past 2 years).
• Symptoms of respiratory dysfunction