Laboratory-Treated T Cells and Ipilimumab in Treating Patients With Metastatic Melanoma

This is an interventional treatment trial for Recurrent Melanoma Read More

Inclusion Criteria:

• Histopathologic documentation of melanoma concurrent with the diagnosis of metastatic disease
• Expression of human leukocyte antigen (HLA)-A2
• Eastern Cooperative Oncology Group (ECOG)/Zubrod performance status of 0-1
• Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study in such a manner that the risk of pregnancy is minimized; suggested precautions should be used to minimize the risk or pregnancy for at least 1 month before start of therapy, and while women are on study for up to 3 months after T cell infusion, and at least 8 weeks after the study drug is stopped; WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or is not postmenopausal
• Men must be willing and able to use an acceptable method of birth control, for at least 3 months after completion of the study, if their sexual partners are WOCBP
• Willing and able to give informed consent
• Adequate venous access-consider peripherally inserted central catheter (PICC) or central line
• Bi-dimensionally measurable disease by palpation on clinical exam, or radiographic imaging (X-ray, computed tomography [CT] scan)
• At least 4 weeks must have elapsed since the last chemotherapy, radiotherapy or major surgery; at least 6 weeks for nitrosoureas, mitomycin C and liposomal doxorubicin; if started before T-cell administration, Ipilimumab infusions must be least 21 days apart
• Toxicity related to prior therapy must either have returned to =< grade 1, baseline, or been deemed irreversible
• Persons of reproductive potential must agree to use and utilize an adequate method of contraception throughout treatment and for at least 8 weeks after study drug is stopped

Exclusion Criteria:

• Patients with active infections or oral temperature > 38.2 C within 72 hours prior to planned leukapheresis; the procedure may be deferred
• Patients with hematocrit (Hct) < 30%, white blood cells (WBC) < 2500/uL and platelets < 50,000 immediately prior to leukapheresis; the procedure may be deferred
• Any other malignancy from which the patient has been disease-free for less than 5 years, with the exception of adequately treated and cured basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix
• White blood cell count (WBC) < 2000/uL
• Hematocrit (Hct) < 24% or hemoglobin (Hb) < 8 g/dL
• Absolute neutrophile count (ANC) < 1000
• Platelets < 50,000
• Creatinine > 3.0 x upper limit normal (ULN)
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) > 2.5 x ULN
• Bilirubin > 3 x ULN
• Pregnant women, nursing mothers, men or women of reproductive ability who are unwilling to use effective contraception; women of childbearing potential with a positive pregnancy test within 3 days prior to entry
• 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 diffusion capacity of carbon monoxide (DLco) (corr for Hgb) < 50% will be excluded

• Significant cardiovascular abnormalities as defined by any one of the following:

  • Congestive heart failure
  • Clinically significant hypotension
  • Symptoms of coronary artery disease
  • Presence of cardiac arrhythmias on electrocardiogram (EKG) requiring drug therapy
  • Ejection fraction < 50 % (echocardiogram or multi gated acquisition [MUGA] scan)
• Active and untreated central nervous system (CNS) metastasis (including metastasis identified during screening magnetic resonance imaging [MRI] or contrast CT)
• Autoimmune disease: Patients with a history of Inflammatory Bowel Disease are excluded from this study, as are patients with a history of autoimmune disease (e.g. systemic lupus erythematosus, vasculitis, infiltrating lung disease) whose possible progression during treatment would be considered by the Investigator to be unacceptable
• Any underlying medical or psychiatric condition, which in the opinion of the Investigator, will make the administration of study drug hazardous or obscure the interpretation of adverse events, such as a condition associated with frequent diarrhea
• Positive screening tests for human immunodeficiency virus (HIV), hepatitis (Hep) B, and Hep C; if positive results are not indicative of true active or chronic infection, the patient can be treated
• Steroids are not permitted 3 days prior to T cell infusion and concurrently during therapy
• No prisoners or children will be enrolled on this study
• Any non-oncology vaccine therapy used for the prevention of infectious disease within 1 month before or after any ipilimumab dose
• Patients may not be on any other treatments for their cancer aside from those included in the protocol; patients may not undergo another form of treatment concurrently with this study