Continuous Infusion of rhIL-15 for Adults With Advanced Cancer
Condition: Lymphoma; Carcinoma
Intervention: rh IL-15 (10 DAYS); rh IL-15 (5 DAYS)
Intervention description: Continuous infusion of recombinant human Interleukin-15 (rh IL-15) intravenous (IV) for first 10 days of each cycle; Continuous infusion of recombinant human Interleukin-15 (rh IL-15) for first 5 days of each cycle
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Enrollment: 38.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Pharmacokinetics of lL-15; Cytokine Therapy; Effects of rhlL-15 on T-cells and NK cells; Immunotherapy

Summary:

      Background:

      - People with cancer can have a weak immune system as a result of the cancer itself, or from
      prior treatments. Still, treatments that stimulate the immune system have been shown to be
      effective against a number of different cancers. Recombinant human interleukin-15 (rhIL-15)
      is a drug that is designed to boost the immune system. Researchers are interested in seeing
      if rhIL-15 can strengthen the immune system's response against cancer. The drug will be given
      through a vein without a break for 10 days (240 hours).

      Objectives:

        -  To see rhIL-15 given as a continuous infusion over 10 days can be used to treat advanced
           cancer

        -  Identify the side effects associated with this treatment.

      Eligibility:

      - Individuals at least 18 years of age with advanced cancer for which there are no effective
      treatments.

      Design:

        -  Participants screening procedures will include a physical exam and medical history,
           laboratory (blood) tests and x-rays (Imaging studies) to determine suitability for the
           protocol.

        -  Appropriate participants with easily accessible tumor deposits may also be asked to have
           one pretreatment and one post (cycle 1) treatment tumor biopsy.

        -  Eligible participants will be admitted to the hospital for the rhIL-15 treatment and
           will spend about 12 days in the hospital.

        -  Participants will receive one 10 day infusion each cycle (about every 42 days) for as
           long as there are no serious side effects and the disease does not progress.

        -  Participants will continue treatment as long as imaging studies show that the tumor
           continues to shrink or for two additional cycles after it has disappeared from the
           x-rays to make that the cancer is completely gone.

        -  Participants who stop treatment for side effects or because their tumor did not shrink
           or stopped responding to the treatment will continue to have follow-up visits to monitor
           the outcome of the rhIL-15 treatment until there is evidence their cancer has progress
           or they begin another treatment.
    

Eligibility criteria:

        -  INCLUSION CRITERIA

          -  Age greater than or equal to 18 years.

          -  Patients must have histologically confirmed (by the National Cancer Institute (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 computed tomography (CT) scan.

          -  Patients must have recovered to < grade 1 Common Terminology Criteria for Adverse
             Events (CTCAE)v4 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 7-hydroxystaurosporine (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.

          -  Diffusing capacity for carbon monoxide (DLCO)/alveolar volume (VA) and forced
             expiratory volume (FEV)-1.0 > 60% of predicted on pulmonary function tests.

          -  Serum creatinine of less than or equal to 1.5 X the upper limit of normal.

          -  Aspartate aminotransferase (AST) and alanine aminotransferase (AST) < 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 Eastern Cooperative
             Oncology Group (ECOG) less than or equal to 1

          -  Subjects with inactive central nervous system (CNS) metastasis are eligible. Inactive
             CNS metastasis is defined as: no signs of cerebral edema after successful definitive
             treatment of brain metastases (surgical resection, whole brain irradiation,
             stereotactic radiation therapy, or a combination of these) with stable or improved
             radiographic appearance on magnetic resonance imaging (MRI) scan at least 1 month
             after completion of treatment.

        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,
             monoclonal antibodies or major surgery in the 4 weeks prior to the start of the study.

          -  Life expectancy of less than 3 months.

          -  Patients with more than 30% replacement of hepatic parenchyma by tumor or any history
             of drug related hepatic encephalopathy.

          -  History of complex ventricular or supraventricular arrhythmias

          -  Documented human immunodeficiency virus (HIV), active bacterial infections, active or
             chronic hepatitis B, or hepatitis C infection.

          -  A positive hepatitis B serology indicative of previous immunization (i.e., hepatitis B
             surface antigen (HBsAb) positive and hepatitis B core antibody (HBcAb) 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 central nervous system (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 controlled with inhaled bronchodilators are
             eligible).

          -  History of autoimmune disease, with the exception of an autoimmune event associated
             with prior ipilimumab (anti-cluster of differentiation 152 (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.