| Eligibility |
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
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