Protocol Number: 08-C-0104

Title:

Phase II Study in Patients with Metastatic Melanoma Using a Non-Myeloablative Lymphocyte Depleting Regimen of Chemotherapy Followed by Infusion of gp100 Reactive Peripheral Blood Lymphocytes (PBL) and High or Low Dose Aldesleukin

Number:

08-C-0104

Summary:

Background:

This study uses a new experimental procedure for treating melanoma that uses the patient's own lymphocytes (type of white blood cell), which are specially selected to target and destroy their tumor.

Objectives:

To determine whether this experimental treatment can cause the patient's tumor to shrink.

To test the safety of the treatment and its effects on the immune system.

Eligibility:

Patients with metastatic melamona 18years of age and older for whom standard treatments are not effective or who cannot take high-dose interleukin-2 (IL-2).

Patients must have the tissue type HLA-A0201.

Design:

Workup: Patients have scans, x-rays, laboratory tests, and other tests as needed.

Patients have leukapheresis (a procedure for collecting lymphocytes that is similar to collecting whole blood) to collect cells for laboratory treatment and later reinfusion.

Chemotherapy: Patients have low-dose chemotherapy for 1 week to prepare the immune system to receive the cultured lymphocytes.

Cell infusion and IL-2 treatment: Patients receive the lymphocytes by infusion through a vein and then either high-dose IL-2 infused through a vein or low-dose IL-2 injected under the skin. High-dose IL-2 is given as infusions through a vein every 8 hours for up to 15 doses. Low-dose IL-2 is given as injections under the skin daily for 5 days, followed by a 2-day rest, with this regimen repeated for a total of 5 weeks.

Recovery: Patients rest for 1 to 2 weeks to recover from the effects of chemotherapy and IL-2.

Tumor biopsy: Patients may be asked to have a biopsy (removal of a small piece of tumor) after receiving treatment to look at the effects of treatment in the tumor.

Follow-up: After treatment is completed, patients return to the clinic for physical examinations, review of side effects, laboratory tests and scans every 1 to 6 months until the disease worsens.

Retreatment: Patients whose tumor did not grow after treatment or showed evidence of shrinking may be able to be retreated if their tumor begins to grow. They receive the same regimen of chemotherapy, lymphocyte infusion and IL-2 treatment.

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. The diagnosis of metastatic melanoma and positivity for gp100 will be confirmed by the Laboratory of Pathology of the NCI.

b. Patients must be refractory to high dose aldesleukin treatment if they are medically eligible to receive it. Patients with ocular melanoma are not required to be refractory to high dose aldesleukin.

c. gp100:154-162 reactive peripheral blood lymphocytes derived from a leukapheresis.

d. HLA-A*0201 positive.

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

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

g. Life expectancy of greater than three months.

h. Willing to sign a durable power of attorney.

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

j. Clinical performance status of ECOG 0 or 1 for the high dose aldesleukin cohort or ECOG 0, 1 or 2 for the low dose aldesleukin cohort.

k. Hematology:

- Absolute neutrophil count greater than 1000/mm3 without support of filgrastim

- Normal WBC (greater than 3000/mm3).

- Hemoglobin greater than 8.0 g/dl

- Platelet count greater than 100,000/mm3.

l. 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.

m. Chemistry:

- Serum ALT/AST less than less or equal to 2.5 times the upper limit of normal.

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

- Total bilirubin less than or equal to 2.0 mg/dl, except in patients with Gilbert's Syndrome who must have a total bilirubin less than 3 mg/dl.

n. 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.

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

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

EXCLUSION CRITERIA:

a. Systemic steroid therapy required.

b. 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.

c. Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease).

d. 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.)

e. History of severe immediate hypersensitivity reaction to any of the agents used in this study.

f. The following patients will be excluded from the high-dose IL-2 arm (but will be eligible for the low-dose arm):

1. History of coronary revascularization or ischemic symptoms

2. Any patient known to have an LVEF less than or equal to 45%.

3. Documented LVEF of less than or equal to 45% 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

4. Documented FEV1 less than or equal to 60% predicted tested in patients with:

- A prolonged history of cigarette smoking (20 pk/yrs of smoking)

- Symptoms of respiratory dysfunction.

Special Instructions:

Currently Not Provided

Keywords:

Malignant Melanoma

HLA-A2

Immunotherapy

Clinical Response

Recruitment Keyword(s):

Malignant Melanoma

Skin Cancer

Condition(s):

Skin Cancer

Metastatic Melanoma

Investigational Drug(s):

gp100 Reactive PBL

Investigational Device(s):

None

Intervention(s):

Drug: gp100 Reactive PBL

Drug: Aldesleukin

Supporting Site:

National Cancer Institute

Contact(s):

NCI Referral Office
National Institute of Health Clinical Center (CC), 9000 Rockville Pike, Bethesda, Maryland 20892, United States: NCI Clinical Trials Referral Office
Phone: 1-888-NCI-1937
Fax: Not Listed
Electronic Address: ncicssc@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 1;109(3):455-64. Review.

Rosenberg SA. Progress in human tumour immunology and immunotherapy. Nature. 2001 May 17;411(6835):380-4. Review.

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