Protocol Number: 06-C-0169

Title:

Phase II Study in Metastatic Melanoma or Kidney Cancer using Autologous Natural Killer Cells Plus Aldesleukin (IL-2) Following a Lymphodepleting Chemotherapy

Number:

06-C-0169

Summary:

Background:

-Natural killer (NK) cells are large lymphocytes (a type of white blood cell) that are important in the immune response to cancer.

-IL-2 (Aldesleukin) is a substance the body makes that controls the growth and function of many types of cells. The Food and Drug Administration has approved IL-3 for treating metastatic melanoma and kidney cancer. (Metastatic disease is cancer that has spread beyond the primary site.)

Objectives: To determine the safety and effectiveness of treating metastatic melanoma and kidney cancer with laboratory-treated NK cells and IL-2.

Eligibility: Patients 18 years of age or older with metastatic melanoma or kidney cancer who have previously been treated with high-dose IL-2.

Design:

-Leukapheresis. Patients under leukapheresis to obtain NK cells for the treatment regimen. Blood is collected through a needle in an arm vein and directed through a cell separator machine where white blood cells are extracted. The rest of the blood is returned to the patient through a needle in the other arm. NK cells are removed from the white blood cells and treated for re-infusion into the patient.

-Chemotherapy. Starting 8 days before infusion of the treated NK cells, patients receive intravenous (IV, through a vein) infusions of cyclophosphamide and fludarabine to suppress the immune system.

-NK cell infusion. Patients receive a 30-minute IV infusion of NK cells 2 days after the last dose of chemotherapy.

-IL-2 therapy. Within 24 hours of the NK cell infusion, patients receive high-dose IL-2 as a 15-minute IV infusion every 8 hours for up to 5 days. A second cycle of IL-2 is given about 14 days after the first.

-Blood tests and biopsy. Patients have frequent blood tests during the treatment period and may be asked to undergo a biopsy (surgical removal of a small piece of tumor or lymph node) at the end of treatment to look at the effects of the treatment on the tumor immune cells.

-Follow-up evaluation. Patients are evaluated 4-6 weeks after completing treatment. They have a physical examination, scans of tumor sites, blood tests and blood sampling (or leukapheresis) to examine the response to treatment. Patients who improve with treatment return for evaluations every month. Those whose tumor grows again after originally shrinking may receive one additional treatment course.

Sponsoring Institute:

National Cancer Institute (NCI)

Recruitment Detail

Type: Participants currently recruited/enrolled

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): Children

Eligibility Criteria:

INCLUSION CRITERIA:

a. Patients must have previously received high dose IL-2 and have been either non-responders (progressive disease) or have recurred.

b. Patients who are greater than or equal to 18 years of age, must have measurable metastatic melanoma or metastatic kidney cancer and no tumor reactive T cells available for cell transfer therapy.

c. Pathology for metastatic melanoma or metastatic kidney cancer to be confirmed by the NCI Laboratory of Pathology.

d. Patients of both genders must be willing to practice birth control for four months after receiving the preparative regimen.

e. Clinical performance status of ECOG 0, 1.

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

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

g. Hemoglobin greater than 8.0 g/dl.

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

i. Serum creatinine less than or equal to 1.6 mg/dl.

j. 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.

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

EXCLUSION CRITERIA:

a. Less than four weeks has elapsed since any prior systemic therapy at the time the patient receives the preparative regimen, or less than six weeks since prior nitrosurea therapy.

b. Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant.

c. Life expectancy of less than three months.

d. Systemic steroid therapy required.

e. Any active systemic infections, coagulation disorders or other major medical illnesses of the cardiovascular, respiratory or immune system, as evidenced by a positive stress thallium or comparable test, myocardial infarction, cardiac arrhythmias, obstructive or restrictive pulmonary disease.

f. Any form of autoimmune disease (such as autoimmune colitis or Crohn's Disease).

g. Seropositive for HIV antibody. (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who are HIV seropositive can have decreased immune competence and thus be less responsive to the experimental treatment and more susceptible to its toxicities.)

h. Seropositive for hepatitis B or C antigen.

j. Patients who are not eligible to receive high-dose Aldesleukin as evaluated by the following:

1) Patients who are 50 years old or greater who do not have a normal stress cardiac test (stress thallium, stress MUGA, dobutamine echocardiogram, or other stress test) will be excluded.

2) Patients who have history of EKG abnormalities, symptoms of cardiac ischemia or arrhythmias who do not have a normal stress cardiac test (stress thallium, stress MUGA, dobutamine echocardiogram, or other stress test) will be excluded.

3) Patients with a prolonged history of cigarette smoking or symptoms of respiratory dysfunction who do not have a normal pulmonary function test as evidenced by a FEV1 less than 60% predicted will be excluded.

4) Patients who experienced toxicities during prior IL-2 administration that would preclude redosing with IL-2, i.e. myocardial infarction, mental status changes requiring intubation, bowel perforation or renal failure requiring dialysis.

j. Prior treatment with anti-CTLA-4 antibody will be excluded unless a post anti-CTLA-4 antibody treatment colonoscopy was normal with normal colonic biopsies.

Special Instructions:

Currently Not Provided

Keywords:

Adoptive Cell Therapy

Cutaneous Melanoma

Clinical Response

Rate of Repopulation

Toxicity Profile

Recruitment Keyword(s):

Metastatic Melanoma

Metastatic Kidney Cancer

Condition(s):

Metastatic Melanoma

Metastatic Kidney Cancer

Investigational Drug(s):

Natural Killer (NK) Lymphophocytes

Investigational Device(s):

None

Intervention(s):

Drug: Natural Killer (NK) Lymphophocytes

Supporting Site:

National Cancer Institute

Contact(s):

Recruitment Center - SB
National Institute of Health Clinical Center (CC), 9000 Rockville Pike, Building 10, Room 2-1730, Bethesda, Maryland 20892, United States
Phone: (866) 820-4505
Fax: (301) 451-1927
Electronic Address: ncisbirc@mail.nih.gov

Citation(s):

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.

Dudley ME, Wunderlich JR, Robbins PF, Yang JC, Hwu P, Schwartzentruber DJ, Topalian SL, Sherry R, Restifo NP, Hubicki AM, Robinson MR, Raffeld M, Duray P, Seipp CA, Rogers-Freezer L, Morton KE, Mavroukakis SA, White DE, Rosenberg SA. Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes. Science. 2002 Oct 25;298(5594):850-4. Epub 2002 Sep 19.

Berendt MJ, North RJ. T-cell-mediated suppression of anti-tumor immunity. An explanation for progressive growth of an immunogenic tumor. J Exp Med. 1980 Jan 1;151(1):69-80.

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