INCLUSION CRITERIA:
a. Age greater or equal to 18 years of age.
b. Patients must have metastatic melanoma, metastatic renal cell carcinoma or locally advanced non resectable renal cell carcinoma which is incurable and which is refractory to standard therapy, or the patient must be ineligible to receive standard therapy for their disease. Refractory cancers can be defined as a tumor which either does not respond or progresses after standard treatment.
c. Patients with a metastatic melanoma or metastatic renal cell carcinoma must have previously received high dose IL-2 or have a contra-indication for this treatment.
d. A histologically confirmed diagnosis of melanoma or renal cell carcinoma confirmed by the NIH Laboratory of Pathology.
e. Patients must have measurable or evaluable disease according to RECIST criteria.
f. AST and ALT less than or equal to 2.5 times the upper limit of normal (ULN).
g. Conjugated (direct) bilirubin less than or equal to 1.25 ULN.
h. Absolute Neutrophil Count greater than 1000 / mm(3).
i. Platelets greater than 100,000/ mm(3).
j. PT/PTT within 1.5 x ULN.
k. Serum Creatinine less than 1.5 x ULN.
l. ECOG performance status less than or equal to 2.
m. Patients who are 50 years old or older must have a normal stress cardiac test (stress thallium, stress MUGA, dobutamine echocardiogram, or other stress test) as evidenced by LVEF greater than or equal 45%.
n. Patients who have a history of EKG abnormalities, symptoms of cardiac ischemia must have a normal stress cardiac test (stress thallium, stress MUGA, dobutamine echocardiogram, or other stress test) as evidenced by LVEF greater than or equal to 45%.
o. Patients who have a familial or personal history of heart failure or received antimitotic agents susceptible to trigger heart failure must have a normal stress MUGA or dobutamine echocardiogram as evidenced by LVEF greater than or equal to 45%.
p. Patients with a prolonged history of cigarette smoking or symptoms of respiratory dysfunction must have a normal pulmonary function test as evidenced by a FEV1 greater than 60% predicted.
q. Patients in cohort 1 must have a CD3+ cell count greater than 400 cells per mm(3) and CD4+ cell count greater than 400 cells per mm(3) in the peripheral blood.
r. Patients in cohort 2 must have a CD4+ cell count less than 400 cells per mm(3) in the peripheral blood.
s. Patients must not have received any systemic corticosteroid therapy within the two weeks prior to the initiation of study treatment.
t. Patients must not have received any cytotoxic therapy, immunotherapy by cytokines, anti-tumor vaccines or monoclonal antibody in the four weeks prior to the initiation of study treatment.
EXCLISION CRITERIA:
a. Life expectancy less than three months.
b. Current need for palliative therapy as determined by the principal investigator.
c. Documented HIV, hepatitis B, hepatitis C or acute hepatitis A infection.
1. A positive hepatitis B serology indicative of previous immunization (i.e. HBs Ab positive and HBc Ab negative) is not an exclusion criterion.
2. A positive hepatitis C serology is not an exclusion criterion if the HCV RNA load, tested by PCR, is negative.
d. Documented cirrhosis or documented acute hepatitis including hepatitis A virus infection or acute alcoholic hepatitis or documented chronic hepatitis including Non-alcoho,ic Hepato-Steatitis (NASH).
e. Splenic metastasis.
f. Acetaminophen within 24 hours of first injection.
g. Drugs which are known to be potentially hepatotoxic are prohibited within 7 days prior to the first injection except for an indication regrded as medically necessary by the Principal Investigator.
h. Any alcohol within 48 hours prior to the first injection.
i. Concurrent cytotoxic or immunosuppressive therapies.
j. Medical need for chronic anticoagulation (coumadin 1 to 2 mg/day is acceptable, heparin not acceptable).
k. Patients with a resting blood pressure greater than 140/90, in presence of standard anti-hypertensive therapy. Untreated hypertensive patients may be given a trial of standard anti-hypertensive therapy and, if their hypertension is well controlled, may be allowed to enter the study.
l. QTc prolongation defined as a QTc greater than or equal to 470 ms or a prior history of cardiovascular disease, arrhythmias, or significant ECG abnormalities.
m. Patients with brain metastases which were not previously treated or are unstable; patients with treated or stable brain metastases are eligible at the discretion of the investigator.
n. Active infection requiring systemic treatment and/or hospitalization until the patient either completes therapy or is clinically stable on therapy in the opinion of the investigator, for at least 28 days prior to study entry.
o. History of autoimmune disease.
p. History of severe asthma, presently on chronic medications.
q. Prior allogeneic hematopoietic stem cell transplantation or solid organ transplantation.
r. Patients with splenectomy.
s. Current splenomegaly or proliferative hematologic disease.
t. Inability or refusal to practice contraception during therapy or pregnancy.
u. History of medical or psychiatric disease which, in the view of the principal investigator, would preclude safe treatment.
v. Patients with cognitive impairment or likely to develop cognitive impairment while on study.
w. Inability to give informed consent.
National Institutes of Health Clinical Center
Bethesda, Maryland 20892. Last update: 01/30/2009