Continuous Infusion of rhIL-15 for Adults With Advanced Cancer

• INCLUSION CRITERIA
• Age greater than or equal to 18 years.
• Patients must have histologically confirmed (by the NCI Pathology Department) solid tumor malignancy or lymphoma that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are associated with minimal patient survival benefit (as defined the Metabolism Branch physicians or if the patient refuses standard of care treatment ). Enrollment of patients with tumors that can be safely biopsied is encouraged.
• Patients must have evaluable or measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as greater than or equal to 20 mm with conventional techniques or as greater than or equal to 10 mm with spiral CT scan.
• Patients must have recovered to < grade 1 CTCAEv4 from toxicity of prior chemotherapy or biologic therapy and must not have had prior chemotherapy or biologic therapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C, 8 weeks for UCN-01).
• Patients must be at least 1 month since any prior radiation or major surgery.
• Patients on bisphosphonates for any cancer or on hormone therapy for prostate cancer will not need to discontinue this therapy to be eligible. However, patients with prostate cancer will need to have metastatic prostate cancer that has progressed despite hormonal therapy. Castrate testosterone levels occur within hours after castration and within 2 to 3 weeks of a luteinizing hormone-releasing hormone agonist. The current standard is to continue androgen suppression despite progressive disease.
• DLCO/VA and FEV-1.0 > 50% of predicted on pulmonary function tests.
• Serum creatinine of less than or equal to 1.5 X the upper limit of normal.
• AST and ALT < 2.5 x the upper limit of normal.
• Absolute neutrophil count greater than or equal to 1,500/mm(3) and platelets greater than or equal to 100,000/mm(3).
• Karnofsky performance status greater than or equal to 70% or ECOG less than or equal to 1
• CNS metastases: Patients who remain asymptomatic after successful definitive treatment of brain metastases (i.e., surgical resection, curative whole brain irradiation, stereotactic radiation therapy, or a combination of these) demonstrating stable or improved radiographic appearance on MRI scan at least 3 months after completion of treatment with no signs of cerebral edema are eligible.

EXCLUSION CRITERIA:

• Patients who have received any systemic corticosteroid therapy within 3 weeks prior to the start of therapy with the exception of physiological replacement doses of cortisone acetate or equivalent.
• Patients who have received any cytotoxic therapy, immunotherapy, antitumor vaccines or monoclonal antibodies in the 4 weeks prior to the start of the study.
• Life expectancy of less than 3 months.
• Documented HIV, active bacterial infections, active or chronic hepatitis B, hepatitis C or HTLV-I infection.
• A positive hepatitis B serology indicative of previous immunization (i.e., HBsAb positive and HBc Ab negative), or a fully resolved acute hepatitis B infection is not an exclusion criterion.
• A positive hepatitis C serology is an exclusion criterion.
• Concurrent anticancer therapy (including other investigational agents), with the exception of hormone therapy for prostate cancer.
• Active CNS metastases (inactive CNS metastases are defined).
• History of severe asthma or presently on chronic inhaled corticosteroid medications (patients with a history of mild asthma not requiring therapy are eligible).
• History of autoimmune disease, with the exception of an autoimmune event associated with prior ipilimumab (anti-CTLA-4) therapy that has been completely resolved for more than 4 weeks.
• Inability or refusal to practice effective contraception during therapy or the presence of pregnancy or active breastfeeding (men and women of childbearing potential must use an effective method of birth control or abstinence during treatment and for 4 months after completion of treatment).
• Cognitive impairment, history of medical or psychiatric disease, other uncontrolled intercurrent illness, active substance abuse, or social circumstances, which in the view of the Principal Investigator (PI), would preclude safe treatment or the ability to give informed consent.