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

• Status: Terminated
• Trial end date: 2012-12-01
• Target enrollment: 0
• Participant gender: All

Summary

Background:

• MAGE-A3/12 is a type of protein commonly found on certain types of cancer cells, particularly in metastatic cancer. Researchers have developed a process to take lymphocytes (white blood cells) from cancer patients, modify them in the laboratory to target cancer cells that contain MAGE-A3/12, and return them to the patient to help attack and kill the cancer cells. These modified white blood cells are an experimental treatment, but researchers are interested in determining their safety and effectiveness as a possible treatment for cancers that involve MAGE-A3/12.

Objectives:

• To evaluate the safety and effectiveness of anti-MAGE-A3/12 lymphocytes as a treatment for metastatic cancers that have not responded to standard treatment.

Eligibility:

• Individuals at least 18 years of age who have been diagnosed with metastatic melanoma, renal cell cancer, or another type of metastatic cancer that has not responded to standard treatment.

Design:

• Participants will be screened with a full medical history and physical examination, as well as blood and urine tests, tumor samples, and imaging studies.

• Participants will have leukapheresis to collect enough white blood cells for modification in the laboratory.

• Seven days before the start of anti-MAGE-A3/12 treatment, participants will have chemotherapy with cyclophosphamide and fludarabine to suppress the immune system in preparation for the treatment.

• After the last dose of chemotherapy, participants will receive the anti-MAGE-A3/12 cells as an infusion for 20 to 30 minutes, followed by a dose of interleukin-2 to keep the anti-MAGE-A3/12 cells alive and active as long as possible. Participants will also receive filgrastim to encourage the production of blood cells.

• Participants will remain in the hospital to be monitored for possible side effects, and after release from the hospital will have regular followup exams with blood samples and imaging studies to evaluate the effectiveness of the treatment....

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Cancer Institute (NCI)
• Treatments: Aldesleukin; Cyclophosphamide; Fludarabine; Fludarabine phosphate

Criteria

• 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