Vaccine Therapy Following Therapeutic Autologous Lymphocytes and Cyclophosphamide in Treating Patients With Metastatic Melanoma

PRIMARY OBJECTIVES:

I. Assess the safety and toxicity of T-APC vaccination following adoptive T cell therapy.

II. Evaluate the functional and numeric in vivo persistence of adoptively transferred cytotoxic t lymphocytes (CTL) followed by T-APC vaccination.

SECONDARY OBJECTIVES:

I. Evaluate the antitumor effect of adoptive T cell therapy followed by T-APC vaccination.

OUTLINE : This is a dose-escalation study of T-APC vaccine.

INFUSION I: Patients receive high-dose cyclophosphamide intravenously (IV) on days -4 and -3 and low-dose aldesleukin (IL-2) subcutaneously (SC) twice daily (BID) on days 0-14. Patients also receive CTL IV on day 0.

INFUSION II: Beginning 6-48 hours later, patients receive high-dose cyclophosphamide, low-dose IL-2, and CTL as in Infusion I. Patients also receive T-APC vaccine IV within 18-36 hours following CTL infusion and in week 4, and IL-2 SC BID on days 0-14 following second T-APC vaccination.

After completion of study treatment, patients are followed up for 8 weeks.

Inclusion criteria

• Histopathological documentation of melanoma concurrent with the diagnosis of metastatic disease
• Tumor expression of melanocyte differentiation antigen (MDA: MART-1 = 2+ staining or > 25%) by immunohistochemistry (IHC)
• Expression of human leukocyte antigen (HLA)-A201
• Zubrod performance status of '0-1' at the time of treatment
• Bi-dimensionally measurable disease by palpation on clinical exam, or radiographic imaging (X-ray, computed tomography [CT] scan)
• Normal cardiac stress test will be required for all patients with any history of cardiac disease

Exclusion criteria

• Pregnant women, nursing mothers, men or women of reproductive ability who are unwilling to use effective contraception or abstinence; women of childbearing potential must have a negative pregnancy test within two weeks prior to entry
• Serum creatinine > 1.6 mg/dL or Creatinine clearance < 75 ml/min
• Serum glutamic oxaloacetic transaminase (SGOT) > 150 IU or > 3x upper limit of normal
• Bilirubin > 1.6 mg/dL
• Prothrombin time > 1.5 x control
• Clinically significant pulmonary dysfunction, as determined by medical history and physical exam; patients so identified will undergo pulmonary functions testing and those with forced expiratory volume in one second (FEV1) < 2.0 L or carbon monoxide diffusing capacity (DLco) (corr for hemoglobin [Hgb]) < 75% will be excluded
• Congestive heart failure
• Clinically significant hypotension
• Symptoms of coronary artery disease
• Presence of cardiac arrhythmias on electrocardiograph (EKG) requiring drug therapy
• Ejection fraction < 50 % (echocardiogram or multi gated acquisition scan [MUGA])
• Symptomatic central nervous system metastases greater than 1 cm at time of therapy; patients with 1-2 asymptomatic, less than 1 cm brain/central nervous system (CNS) metastases without significant edema may be considered for treatment
• Patients with active infections or oral temperature > 38.2 C within 72 hours of study entry or systemic infection requiring chronic maintenance or suppressive therapy
• Chemotherapeutic agents (standard or experimental), radiation therapy, or other immunosuppressive therapies less than 3 weeks prior to T cell therapy; (patients with bulky disease may undergo cytoreductive chemotherapy but treatment will be discontinued at least 3 weeks prior to T cell therapy)
• Clinically significant autoimmune disorders or conditions of immunosuppression; patients with acquired immune deficiency syndrome (AIDS) or human immunodeficiency virus (HIV)-1 associated complex or known to HIV antibody seropositive or known to be recently polymerase chain reaction (PCR)+ for hepatitis are not eligible for this study; virology testing will be done within 6 months of T cell infusion; the severely depressed immune system found in these infected patients and the possibility of premature death would compromise study objectives
• Chemotherapeutic agents (standard or experimental), radiation therapy, or other immunosuppressive therapies less than 3 weeks prior to T cell therapy
• Current treatment with steroids
• Patients must not be receiving any other experimental drugs within 3 weeks of the initiation of the protocol and must have recovered from all side effects of such therapy
• Patients for whom we are unable to generate MART-1 specific T cells