Biological Therapy in Treating Patients With Metastatic Melanoma

Fred Hutchinson Cancer Center (FHCC)

Status and phase

Completed

Phase 1

Conditions

Melanoma (Skin)

Treatments

Biological: therapeutic tumor infiltrating lymphocytes

Biological: aldesleukin

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00045149

FHCRC-1588.00

1588.00

NCI-H02-0091

CDR0000256451 (Registry Identifier)

Details and patient eligibility

About

RATIONALE: Biological therapies such as cellular adoptive immunotherapy use different ways to stimulate the immune system and stop cancer cells from growing. Treating a person's white blood cells in the laboratory and then reinfusing them may cause a stronger immune response and kill more tumor cells.

PURPOSE: Phase I trial to study the effectiveness of biological therapy in treating patients who have metastatic melanoma.

Full description

OBJECTIVES:

Primary

Determine the safety and toxicity of cellular adoptive immunotherapy comprising autologous CD8+ cytotoxic T-lymphocyte clones targeting cancer-testis antigens in patients with metastatic melanoma.
Determine the duration of in vivo persistence of this therapy in these patients.

Secondary

Evaluate the antitumor effects of this therapy in these patients.

OUTLINE: Patients undergo leukapheresis to obtain peripheral blood mononuclear cells and then CD8+ cytotoxic T-lymphocyte (CTL) clones are generated ex vivo. Patients receive cellular adoptive immunotherapy comprising autologous CD8+ CTL clones targeting cancer testis antigens IV over 30 minutes on day 1. Patients also receive interleukin-2 subcutaneously every 12 hours on days 1-14 of courses 2-4. Treatment repeats every 3 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Patients who demonstrate a clinical response after completion of the fourth course are eligible to receive additional T-cell infusions.

Patients are followed for 9 months.

PROJECTED ACCRUAL: A total of 20 patients will be accrued for this study within 3 years.

Sex

All

Ages

18 to 75 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

Histologically confirmed metastatic melanoma
- Stage IV disease
HLA-A1, -A2, and -A3 positive
MAGE-1 or -3 positive by histology
Bidimensionally measurable disease by palpation on clinical examination, x-ray, or CT scan
No CNS metastases

PATIENT CHARACTERISTICS:

Age

18 to 75

Performance status

Karnofsky 80-100%

Life expectancy

More than 6 months

Hematopoietic

Not specified

Hepatic

Bilirubin ≤ 1.6 mg/dL
SGOT ≤ 3 times upper limit of normal
PT ≤ 1.5 times control

Renal

Creatinine ≤ 2.0 mg/dL
Calcium ≤ 12 mg/dL

Cardiovascular

No congestive heart failure
No clinically significant hypotension
No symptoms of coronary artery disease
No cardiac arrhythmias on electrocardiogram requiring drug therapy
Patients with prior cardiovascular disease or the presence of any of the above abnormalities undergo a cardiac evaluation, which may include a stress test and/or echocardiogram

Pulmonary

No clinically significant pulmonary dysfunction by medical history or physical examination
FEV_1 ≥ 60% of normal
DLCO ≥ 55% (corrected for hemoglobin)

Other

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No retinitis or choroiditis
No active infections or oral temperature greater than 38.2 degrees Celsius within the past 72 hours
No systemic infection requiring chronic maintenance or suppressive therapy

PRIOR CONCURRENT THERAPY:

Biologic therapy

No other concurrent immunotherapy (e.g., other interleukins, interferons, melanoma vaccines, intravenous immunoglobulin, or expanded polyclonal tumor-infiltrating lymphocytes or lymphokine-activated killer cell therapy)

Chemotherapy