Ultra Low Dose Interleukin-2 in Healthy Volunteers
Condition: Hematologic Diseases
MeSH terms: Hematologic Diseases
Study type: Interventional
Phase: Phase 1

Summary: 
      Background:

      - Interleukin-2 is a drug that can help stimulate the body s response to inflammation. High
      dose interleukin-2 has been used to treat different types of cancer and immune system
      disorders. However, it can cause frequent and often serious side effects at the doses
      currently used for treatment. Very low dose interleukin-2 (700 folds less than regular dose)
      was previously tested in cancer patients and stem cell transplant recipients. The study
      observed important immune changes and minimal side effects in those patients. Researchers
      want to test the healthy immune system's responses to very low doses of interleukin-2 to
      better understand how the drug works.

      Objectives:

      - To study the effects of very low doses of interleukin-2 on healthy volunteers.

      Eligibility:

      - Healthy volunteers at least 18 years of age.

      Design:

        -  Participants will be screened with a medical history and physical exam. They will also
           have blood and urine samples.

        -  Participants will receive one of two possible very low doses of interleukin-2 every day
           for 5 days.

        -  Blood samples will be taken twice before the first dose, 1 day after the first dose, and
           before the next three doses. Followup blood samples will be taken on Days 7, 14, and 28
           after the first dose.
    

Detailed description: 
      Interleukin 2 (IL-2, aldesleukin) was discovered as a T cell growth factor more than 30 years
      ago. IL-2 was the first human cytokine used therapeutically. IL-2 induces antigen specific T
      cells, and two important lymphocyte subsets: regulatory T cells (T-regs) and natural killer
      cells (NK) cells. T-regs have a critical role in self-tolerance and pathogenesis of
      autoimmune disease or graft versus host disease (GVHD), and they have been extensively
      studied in solid tumors, hematologic malignancies, viral hepatitis, and HIV infections. NK
      cells have a unique role in bridging innate and adaptive immunity. NK cells facilitate
      hematopoietic stem cell (HSC) engraftment reduce GVHD and increase graft-versus-leukemia
      (GVL) effects. NK cells have important roles on pathogenesis of malignancies, autoimmune
      disease and AIDS. Conventional dose IL-2 treatment promotes marked expansion of regulatory T
      cells, and NK cells but is associated with significant side effects. However, much lower
      doses of interleukin-2 (0.5- 1MIU/m2/day) which lack significant side effects, also induce
      expansion of T regs and NK cells. These observations suggest that ultra low dose IL-2 would
      be safe and appropriate to give to hematopoietic stem cell donors. The quality of the
      transplant would be improved because the higher dose of T-regs would reduce the risk of GVHD
      while the higher NK cells would augment the GVL effect. The aim of this study is to evaluate
      the safety and the tolerability of ultra low dose IL-2 in healthy volunteer for preferential
      expansion of T-regs and NK cells with a view to extending ultra low dose IL-2 administration
      to stem cell donors. We anticipate that this study will provide valuable information on the
      biology of IL-2 on the human immunome applicable to various human disease conditions,
      including cancer, immunodeficiency disease, autoimmune disease, and hematopoietic stem cell
      transplantation. The proposed IL-2 dose is 2-3 logs lower than the manufacturer s recommended
      dose. We therefore expect that the dose used in this protocol will be well tolerated.
      Nevertheless, because there is little information on the tolerability and safety of IL-2 at
      these ultra low doses, we have structured this study as a safety protocol with stopping rules
      for unacceptable side effects. This is important because we hope to use the safety data
      generated to justify a future protocol giving ultra low dose IL-2 to stem cell donors.
    

Intervention name(s): Interleukin-2 (100,00 IU/m(2) SQ)
Intervention type(s): Drug
Intervention description(s): 100,000 International Units/m2 SQ daily for 5 days
Intervention MeSH terms: Interleukin-2
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Interleukin-2; IL-2; Stem Cells; Regulatory T Cells (T regs); Natural Killer Cells (NK cells); Healthy Volunteer; HV