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The Safety and the Tolerability of Ultra Low Dose Interleukin-2 in Healthy Volunteers

Phase 1
18 Years
Open (Enrolling)
Hematologic Diseases

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Trial Information

The Safety and the Tolerability of Ultra Low Dose Interleukin-2 in Healthy Volunteers

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.

Inclusion Criteria


- Healthy volunteers confirmed by brief history and physical examination and blood work
through the CHI screening protocol

- Males or females ages 18 years or older


- History of inflammatory or autoimmune disease

- History of inflammatory or autoimmune disease in first degree relatives

- History of malignancies

- Recipients of hematopoietic stem cell transplant or solid organ transplant

- History of seizures

- Positive HIV, hepatitis B surface antigen or hepatitis C antibody

- History or clinical signs of cardiac disease including coronary artery disease,
cardiac arrhythmia, congestive heart failure

- History or clinical signs of of pulmonary disease including obstructive lung disease
and asthma

- Active infections requiring systemic antibiotic therapy or anti-viral therapy

- History of systemic fungal or mycobacterial infections

- Use of immune modifying medications, i.e.- non steroidal anti-inflammatory drugs
(aspirin, ibuprofen, naproxen, celecoxib, ketrolac), steroid (prednisone,
dexamethasone, hydrocortisone), chemotherapy (cisplatin, dacarbazine, interferon
alpha, tamoxifen)

- Persons who are alcoholic or abusers of illicit drugs

- Female subjects who are or may be pregnant or lactating

- Psychiatric diagnoses or symptoms, to include hypomania, bipolar disorder, major
depression, or dysthymia

- Abnormal or marginal peripheral blood count that in the opinion of the PI will cause
Hemoglobin and Hematocrit levels to drop as a result of participation in this study

- Liver function tests above the normal laboratory reference range

- Renal function test above the normal laboratory reference range

- Contraindication to interleukin-2 (i.e. hypersensitivity to IL- 2 products, active
coronary artery disease, patients with organ allograft)

- Recent recipient of any type of vaccination (i.e. rotavirus vaccine, BCG, influenza
virus vaccine, rubella virus vaccine, mumps virus vaccine, measles vaccine,
poliovirus vaccine, smallpox vaccine, typhoid vaccine, varicella virus vaccine,
yellow fever vaccine) in the 4 weeks preceding and during active study participation

- Body mass index greater than 35

- Inability to comprehend the investigational nature of the study or provide informed

- Diabetes mellitus or fasting blood glucose of > 100 mg/dL.

- Any drugs or supplements that interfere with blood clotting such as Vit.E, NSAIDS,
Warfarin (Coumadin), ticlopidine (Ticlid), clopidogrel (Plavix)

- Use of iodinated contrast media in the 4 weeks preceding and during active study

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Diagnostic

Outcome Measure:

Safety and tolerability of ultra low dose IL-2

Outcome Time Frame:

4 weeks

Safety Issue:


Principal Investigator

Sawa Ito, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

National Heart, Lung, and Blood Institute (NHLBI)


United States: Federal Government

Study ID:




Start Date:

September 2011

Completion Date:

Related Keywords:

  • Hematologic Diseases
  • Interleukin-2
  • IL-2
  • Stem Cells
  • Regulatory T Cells (T regs)
  • Natural Killer Cells (NK cells)
  • Healthy Volunteer
  • HV
  • Hematologic Diseases



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