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Studies on the Mechanism of Action of High-Dose IL-2 in Metastatic Melanoma and Renal Cell Cancer

Phase 1
18 Years
Open (Enrolling)
Metastatic Melanoma, Renal Cell Cancer

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Trial Information

Studies on the Mechanism of Action of High-Dose IL-2 in Metastatic Melanoma and Renal Cell Cancer


- Although interleukin-2 (IL-2) was approved as standard therapy by the US Food and Drug
Administration for metastasis melanoma and renal cell carcinoma, the mechanism of
action in these patient populations is still not completely understood.

- Methods for studying regulatory T-cells and measuring recently discovered cytokines
were not available during earlier studies of IL-2 administration.


- Explore peripheral blood samples of patients with metastatic renal cell cancer or melanoma
receiving high-dose IL-2 to identify serum protein levels and lymphocyte phenotypes that may
be associated with or predictive of tumor regression.


- Patients with metastatic renal cell cancer or melanoma who are greater than or equal to
18 years of age, with an ECOG of 0 or 1 who have an expected survival greater than
three months.

- Patients with systemic infections, coagulation disorders, or major medical illnesses of
the cardiovascular, respiratory or immune system will be excluded, including patients
with ejection fractions less than 45% or FEV1 or VC less than or equal to 60%

- Patients must not have had prior therapy within 28 days, previous IL-2 therapy, be
pregnant, have untreated or clinically significant tumor involvement of the CNS or
major nerve compression, or have greater than 25% estimated hepatic replacement.


- Aldesleukin 720,000 IU/kg intravenous bolus over 15 minutes every eight hours for up to
12 doses will be administered as a cycle of treatment.

- Seven to 10 days after discharge, a second cycle of treatment will be administered.

- 20 mLs of blood for serum and 20 mLs of blood for peripheral blood cells will be
collected daily during the first cycle of aldesleukin administration and the day
following the last dose. 20 mLs of blood for serum and 50 mLs of blood for cell
separation will be obtained on days 2 through 4 following completion of IL-2
administration. On one of these days, an additional 50 mLs of blood for cell
separation or a 2 hour apheresis may be substituted.

- Approximately two months from the beginning of therapy, a response assessment will be

- Patients with stable or regressing disease will receive a second complete treatment
course. Subsequent courses may be administered if there is evidence of on-going tumor
regression without long-term or irreversible toxicity.

- In the first 5 patients of each diagnosis (metastatic renal cell cancer and melanoma)
the following cytokine levels will be assayed: VEGF, CD40L, FASL, TRAIL, GRO-alpha,
IP10, GM-CSF, IFN-gamma, IFN-alpha, IL-1, IL-5, IL-6, IL-8, IL-10, IL-12, IL-13, IL-15,
TNF-alpha, TNF-beta; and the following phenotypic markers will be studied: CD3, CD4,
CD8, CD16, CD25, CD27, CD28, CD56, CD80, CD95, CD107a, CD152, FoxP3, annexin V.

- After the first 10 patients have been analyzed, the scope of the tests will be narrowed
to those which show a response to IL-2.

- Initially, a total of 127 evaluable patients with melanoma will be enrolled, with a
presumed 15% response rate. With the approval of amendment F, a new accrual ceiling
of 200 patients with metastatic melanoma will be established to complete the proposed

- A total of 100 evaluable patients with renal cell carcinoma will be enrolled with a
presumed 20% response rate.

- Allowing for a small number of inevaluable patients, a total of 200 patients with
melanoma and 110 patients with renal cell carcinoma may be enrolled.

Inclusion Criteria


- Any patient with metastatic, measurable, histologically-proven RCC or melanoma who is
a candidate for high-dose IL-2 therapy.

- Expected survival greater than three months.

- Age greater than or equal to18 years old.

- ECOG less than 2.

- Serum creatinine less than or equal to 1.4 mg/dl or creatinine clearance greater than
or equal to 90 mL/min, and total bilirubin less than or equal to 2.0 mg/dl, except in
patients with Gilbert's Syndrome who must have a total bilirubin less than 3.0 mg/dl.

- Platelet count greater than 100,000/mm(3).

- Absolute neutrophil count greater than 1000/mm(3).

- Serum ALT/AST less than three times the upper limit of normal.

- Must be willing to sign a durable power of attorney.

- Must be willing to practice effective contraception (regardless of gender).

- Must be willing to sign the informed consent document.


- Significant second malignancy within 3 years of protocol entry or likely to require
intervention in the year following protocol entry.

- Significant psychiatric disease which in the opinion of the Principal Investigator
would prevent adequate informed consent or render immunotherapy unsafe or

- Requirement for systemic or inhaled steroid administration (topical therapy is

- Prior therapy within 28 days (except focal radiation for bone lesion).

- Systemic infections, coagulation disorders or evidence of active bleeding, or other
major medical illnesses of the cardiovascular, respiratory or immune system.

- ECOG performance status greater than 2.

- Pregnancy.

- Previous IL-2 therapy.

- Positive HIV antibody titer, Seropositive for hepatitis B or C antigen.

- FEV1 or VC less than or equal to 65% of predicted (pulmonary function screening to be
done in patients with significant smoking history [greater than 20pk/years] or
suspicion of pulmonary disease by history or examination).

- Abnormal stress cardiac exam (to be done in all patients greater than or equal to 60
years old and others as indicated clinically) or active cardiac ischemia or
significantly abnormal EKG.

- Greater than 25% estimated hepatic replacement by tumor or SGOT or SGPT greater than
3x normal.

- Untreated or clinically significant (i.e. because of size or presence of edema) tumor
involvement of the CNS or major nerve compression.

Type of Study:


Study Design:

Primary Purpose: Treatment

Outcome Measure:

Clinical outcome as measured by RECIST

Safety Issue:


Principal Investigator

James C Yang, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

National Cancer Institute (NCI)


United States: Federal Government

Study ID:




Start Date:

March 2006

Completion Date:

February 2014

Related Keywords:

  • Metastatic Melanoma
  • Renal Cell Cancer
  • Serum Protein Levels
  • Lymphocyte Phenotypes
  • Predictive Analysis
  • Serum Cytokines
  • Kidney Cancer
  • Renal Cell Cancer
  • Melanoma
  • Metastatic Melanoma
  • Carcinoma, Renal Cell
  • Kidney Neoplasms
  • Melanoma



National Institutes of Health Clinical Center, 9000 Rockville Pike Bethesda, Maryland  20892