Protocol Number: 04-C-0134

Title:

Phase II Evaluation of Denileukin Diftotox in Patients with Metastatic Melanoma or Metastatic Kidney Cancer

Number:

04-C-0134

Summary:

This study will examine the effectiveness of a drug called denileukin diftitox against melanoma or kidney cancer in patients whose disease has spread beyond the original site. Denileukin diftitox contains part of the diphtheria bacteria and interleukin-2 (IL-2), a substance naturally made by the immune system.

Patients 16 years of age and older with melanoma or kidney cancer who no longer benefit from standard treatments, such as surgery, radiation therapy, and chemotherapy may be eligible for this study. The patient's cancer must have progressed while receiving standard therapy, which may or may not have included IL-2. Candidates are screened with a physical examination and blood and urine tests. An electrocardiogram, chest x-ray, and other imaging tests are done if recent ones are not available.

Participants receive denileukin diftitox in 21-day treatment cycles. For each cycle, the drug is infused through a vein over a 60-minute period for 5 consecutive days, followed by 16-days with no treatment. Patients are hospitalized during the 5 days of infusions. Patients whose tumors shrink or remain stable after completing four treatment cycles (one treatment course), and who do not have significant drug side effects, may be offered up to five additional courses of treatment as long as their tumor continues to respond.

In addition to drug therapy, patients have the following tests and procedures:

- Blood test every day of the infusions to monitor body functions.

- Biopsy (surgical removal of a small piece of tissue) of normal skin and tumor or lymph node to examine the effects of treatment on immune cells in the tumor. (This procedure is optional.)

- Leukapheresis to collect immune cells for examination. This procedure is done before starting treatment and again after every two treatments. Blood is collected through a needle in an arm vein and flows through a catheter (plastic tube) into a machine that separates it into its components by spinning. The lymphocytes (white cells) are removed and the rest of the blood (red cells, plasma and platelets) is returned to the body, through a second needle in the other arm.

- Scans or x-rays may be done after two treatments to check the tumor response.

Patients come to the NIH clinic about 3 weeks after the end of each treatment course for a check-up examination, scans and x-rays, and blood drawing.

Sponsoring Institute:

National Cancer Institute (NCI)

Recruitment Detail

Type: Active Accrual Of New Subjects

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): None

Eligibility Criteria:

INCLUSION CRITERIA:

A. Any patient age equal to or greater than 16 with measurable metastatic melanoma or metastatic kidney cancer has an expected survival of greater than three months will be considered. Patients with resectable local/regional disease would undergo standard treatment with surgical resection and will not be eligible.

B. Patients must have progressed while receiving standard therapy which may include IL-2 if it is indicated given the patient's disease status, or it may not include IL-2 if the patient's clinical status has not required immunotherapy with high dose IL-2.

C. Serum creatinine of 2.0 mg/dl or less.

D. Total bilirubin 2.0 mg/dl or less, except for patients with Gilbert's Syndrome who must have a total bilirubin less than 3.0 mg/dl.

E. WBC 300/mm(3) or greater.

F. Platelet count 90,000 mm(3) or greater.

G. Serum AST/ALT less than 3 times normal.

H. Serum albumin equal to or greater than 2.5 g/dl.

I. ECOG performance status of 0 or 1 or 2.

J. For patients greater than 50 years of age or who have a history of cardiovascular disease, a normal thallium stress test is required.

K. Patients of both genders must be willing to practice effective birth control during this trial.

L. Must be willing to undergo leukapheresis.

EXCLUSION CRITERIA:

Patients will be excluded:

A. who are undergoing or have undergone in the past 3 weeks any other systemic form of therapy for their cancer.

B. have active systemic infections, coagulation disorders, autoimmune disease or other major medical illnesses of the cardiovascular or respiratory systems or any known immunodeficiency disease.

C. who require systemic steroid therapy upon entry into the trial.

D. who are nursing or pregnant (because of possible side effects on the newborn or fetus).

E. who are known to be positive for hepatitis BsAG, hepatitis C or HIV antibody (because of possible immune effects of these conditions).

F. who have any form of primary or secondary immunodeficiency or who have not recovered immune competence after chemotherapy or radiation therapy as evidenced by abnormal lymphocyte counts (less than 500/mm(3)), abnorla WBC (less than 3000/mm(3)), or presence of opportunistic infections. (The experimental treatment being evaluated in this protocol may depend on an intact immune system. Patients who have decreased immune competence may be less responsive to the experimental treatment and more susceptible to its toxicities.)

G. who have a prior history of myocardial infarction or severe coronary artery disease.

H. who have sensitivity to denileukin diftitox or any of its components: diphtheria toxin, IL-2 or excipients.

Special Instructions: Currently Not Provided

Keywords:

Toxicity

Complete Tumor Regression

CD4+CD25+

Intravenous Infusion

Anti-CTLA4

Recruitment Keywords:

Metastatic Melanoma

Metastatic Kidney Cancer

Conditions:

Melanoma

Kidney Neoplasms

Investigational Drug(s):

None

Investigational Device(s):

None

Contacts:

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citations:

Rosenberg SA, Yang JC, White DE, Steinberg SM. Durability of complete responses in patients with metastatic cancer treated with high-dose interleukin-2: identification of the antigens mediating response. Ann Surg. 1998 Sep;228(3):307-19.

PMID: 9742914

Phan GQ, Yang JC, Sherry RM, Hwu P, Topalian SL, Schwartzentruber DJ, Restifo NP, Haworth LR, Seipp CA, Freezer LJ, Morton KE, Mavroukakis SA, Duray PH, Steinberg SM, Allison JP, Davis TA, Rosenberg SA. Cancer regression and autoimmunity induced by cytotoxic T lymphocyte-associated antigen 4 blockade in patients with metastatic melanoma.

Proc Natl Acad Sci U S A. 2003 Jul 8;100(14):8372-7. Epub 2003 Jun 25. PMID: 12826605

Waters CA, Schimke PA, Snider CE, Itoh K, Smith KA, Nichols JC, Strom TB, Murphy JR. Interleukin 2 receptor-targeted cytotoxicity. Receptor binding requirements for entry of a diphtheria toxin-related interleukin 2 fusion protein into cells.

Eur J Immunol. 1990 Apr;20(4):785-91. PMID: 2140788

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