Protocol Number: 07-C-0176

Title:

A Phase II Study Using Short-Term Cultured Anti-Tumor Autologous Lymphocytes Following a Non-Myeloablative Lymphocyte Depleting Chemotherapy Regimen in Metastatic Melanoma

Number:

07-C-0176

Summary:

Background:

-Most therapeutic therapies for metastatic melanoma have focused on the ability of T-cell lymphocytes to kill cells of tumors.

-An adaptive cell transfer therapy has been pioneered, in which cells are grown for a short time in the laboratory. The way they are grown may have a better effect in a patient's body than do other cells that are cultured for a longer time.

Objectives:

-To determine whether tumor-infiltrating lymphocytes (TIL) can be put in cells removed from patients' tumors or blood and then reinfused, with the purpose of shrinking tumors.

-To evaluate safety and effectiveness of the treatment.

Eligibility:

-Patients 18 years of age or older with metastatic cancer melanoma (cancer that has spread beyond the original site).

-Patient's leukocyte antigen type is HLA-A 0201.

Design:

-Patients undergo the following procedures:

--Leukapheresis (on two occasions). This is a method of collecting large numbers of white blood cells. The cells obtained in the first leukapheresis procedure are grown in the laboratory, and the TIL cells (called young TIL cells) are inserted into the cells using an inactivated (harmless) virus in a process called retroviral transduction. Cells collected in the second leukapheresis procedure are used to evaluate the effectiveness of the study treatment.

--Chemotherapy. Patients are given chemotherapy through a vein (intravenously, IV) over 1 hour for 2 days to suppress the immune system so that the patient's immune cells do not interfere with the treatment.

--Treatment with young TIL cells. Patients receive an IV infusion of the treated cells, followed by infusions the drug IL-2, which helps boost the effectiveness of the treated white cells.

--Patients are given support medications to prevent complications such as infections.

--Patients may undergo a tumor biopsy (removal of a small piece of tumor tissue).

--Patients are evaluated with laboratory tests and imaging tests, such as CT scans, 4 to 6 weeks after treatment and then once a month for 3 to 4 months to determine the response to treatment.

--Patients have blood tests at 3, 6, and 12 months and then annually for 5 years.

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. Measurable metastatic melanoma with at least one lesion that is resectable for TIL generation.

b. Patients with one or more brain metastases less than 1 cm each, and any patients with 1 or 2 brain metastases greater than 1 cm must have been treated and stable for 3 months.

c. Greater than or equal to 18 years of age .

d. Willing to practice birth control during treatment and for four months after receiving the preparative regimen.

e. Life expectancy of greater than three months.

f. Willing to sign a durable power of attorney.

g. Able to understand and sign the Informed Consent Document.

h. Clinical performance status of ECOG 0 or 1.

i. Hematology:

-Absolute neutrophil count greater than 1000/mm(3) without support of filgrastim.

-Normal WBC (greater than 3000/ mm(3)).

-Hemoglobin greater than 8.0 g/dl.

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

j. Serology:

-Seronegative 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.)

-Seronegative for hepatitis B or hepatitis C.

k. Chemistry: . Serum ALT/AST less than three times the upper limit of normal. Serum creatinine less than or equal to 1.6 mg/dl. Total bilirubin less than or equal to 2 mg/dl, except in patients with Gilbert's Syndrome who must have a total bilirubin less than 3 mg/dl.

l. Negative pregnancy test in women of child bearing potential because of the potentially dangerous effects of the preparative chemotherapy on the fetus.

m. More than four weeks must have elapsed since any prior systemic therapy at the time the patient receives the preparative regimen, and patients' toxicities must have recovered to a grade 1 or less (except for toxicities such as alopecia or vitiligo). Patients may have undergone minor surgical procedures with the past 3 weeks, as long as all toxicities have recovered to grade 1 or less or as specified in the eligibility criteria in Section 2.1.1.

n. Six weeks must have elapsed since prior MDX-010 therapy to allow antibody levels to decline.

o. Patients who have previously received MDX-010 must have a normal colonoscopy with normal colonic biopsies.

EXCLUSION CRITERIA:

a. Patients eligible for Surgery Branch clinical protocol #06-C-0136 investigating the use of 1200cGy TBI preparative regimen, as long as it remains open to accrual.

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. Systemic steroid therapy required.

d. Active systemic infections, coagulation disorders or other active 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.

e. Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease and AIDS).

f. Opportunistic infections (The experimental treatment being evaluated in this protocol depends 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. History of severe immediate hypersensitivity reaction to any of the agents used in this study.

h. History of coronary revascularization or ischemic symptoms.

i. Any patient known to have an LVEF less than or equal to 45 percent.

j. Documented LVEF of less than or equal to 45 percent tested in patients with:

-Clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block.

-Age greater than or equal to 60 years old.

k. Documented FEV1 less than or equal to 60 percent predicted tested in patients with:

-A prolonged history of cigarette smoking.

-Symptoms of respiratory dysfunction.

Special Instructions:

Currently Not Provided

Keywords:

Clinical Response

Immunotherapy

Cancer

Cytokines

Adoptive Cell Therapy

Recruitment Keyword(s):

Melanoma

Skin Cancer

Malignant Melanoma

Condition(s):

Melanoma

Malignant Melanoma

Melanoma, Experimental

Experimental Melanomas

Investigational Drug(s):

Young Unselected TIL

Investigational Device(s):

None

Intervention(s):

Drug: Young Unselected TIL

Cell Transfer: Young Unselected TIL

Drug: Cyclophosphamide

Drug: Fludarabine

Drug: Aldesleukin

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):

Atkins MB, Kunkel L, Sznol M, Rosenberg SA. High-dose recombinant interleukin-2 therapy in patients with metastatic melanoma: long-term survival update.Cancer J Sci Am. 2000 Feb;6 Suppl 1:S11-4.

Gogas HJ, Kirkwood JM, Sondak VK. Chemotherapy for metastatic melanoma: time for a change? Cancer. 2007 Feb ;109(3):455-64. Review

Rosenberg SA, Yannelli JR, Yang JC, Topalian SL, Schwartzentruber DJ, Weber JS, Parkinson DR, Seipp CA, Einhorn JH, White DE. Treatment of patients with metastatic melanoma with autologous tumor-infiltrating lymphocytes and interleukin 2. J Natl Cancer Inst. 1994 Aug 3;86(15):1159-66

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