CD8+ Antigen-Specific T Cells, Cyclophosphamide, Aldesleukin, and Ipilimumab in Treating Patients With Metastatic Melanoma

This is an interventional treatment trial for Metastatic Melanoma Read More

Inclusion Criteria:

• ELIGIBILITY FOR ENROLLMENT
• 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' at screening visit
• 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 of 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
• Evaluation of v-raf murine sarcoma viral oncogene homolog B (BRAF)V600 mutation status
• Measurable tumor (by Response Evaluation Criteria in Solid Tumors [RECIST] criteria)
• Melan-A (MART) 1 or solute carrier family 45, member 2 (SLC45A2) (+) staining results; (if patients have not had staining test in the past, the test will be run after patient consent is obtained, but before enrollment)
• ELIGIBILITY FOR TREATMENT (INCLUDES CYCLOPHOSPHAMIDE, T CELL, ANTI-CTLA4 INFUSIONS AND SC IL-2)
• ECOG/Zubrod performance status of '0-1'
• 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
• Willing and able to give informed consent.

Exclusion Criteria:

• EXCLUSION FOR ENROLLMENT
• 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
• 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
• Active and untreated central nervous system (CNS) metastasis (including metastasis identified during screening magnetic resonance imaging [MRI] or contrast computed tomography [CT])
• No signs or symptoms of CNS metastases (mets) within the last 30 days (from enrollment evaluation)
• No single lesion larger than 1 cm
• No more than 5 lesions
• 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 B (hep B), and hepatitis C (hep C) (referencing blood draw at leukapheresis screening); if positive results are not indicative of true active or chronic infection, the patient can be treated
• White blood cells (WBC) =< 1000/uL
• Hematocrit (Hct) =< 24% or hemoglobin (Hb) =< 8 g/dL
• Absolute neutrophil count (ANC) =< 500
• Platelets =< 50,000
• Creatinine >= 3.0 x upper limit of normal (ULN)
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) >= 2.5 x ULN
• Bilirubin >= 3 x ULN
• Steroids are not permitted 3 days prior to T cell infusion and concurrently during therapy
• 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
• EXCLUSION CRITERIA FOR TREATMENT
• WBC =< 1000/uL (prior to cyclophosphamide and T cell infusions)
• Hct =< 24% or hemoglobin =< 8 g/dL (prior to cyclophosphamide and T cell infusions)
• ANC =< 500 (prior to cyclophosphamide and T cell infusions)
• Platelets =< 50,000 (prior to cyclophosphamide and T cell infusions)
• Creatinine >= 3.0 x ULN (prior to cyclophosphamide and T cell infusions)
• AST/ALT >= 2.5 x ULN (prior to cyclophosphamide and T cell infusions)
• Bilirubin >= 3 x ULN (prior to cyclophosphamide and T cell infusions)
• 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.
• Steroids are not permitted 3 days prior to T cell infusion and concurrently during therapy.
• 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.

• Active and untreated central nervous system (CNS) metastasis (including metastasis identified during screening MRI or contrast CT):

  • No signs or symptoms of CNS mets within the last 30 days (from enrollment evaluation).
  • No single lesion larger than 1cm
  • No more than 5 lesions