Biological Therapy in Treating Patients With Metastatic Melanoma

Fred Hutchinson Cancer Center (FHCC)

Status and phase: Completed; Phase 2; Phase 1

Conditions: Melanoma (Skin)

Treatments: Biological: therapeutic tumor infiltrating lymphocytes; Biological: aldesleukin

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00002786

NCI-V96-0920

1017.01

CDR0000064846 (Registry Identifier)

FHCRC-1017.01

Details and patient eligibility

About

RATIONALE: Biological therapies use different ways to stimulate the immune system and stop cancer cells from growing.

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

Full description

OBJECTIVES:

• Assess the safety and toxicity of cellular adoptive immunotherapy using autologous CD8+ antigen-specific T-cell clones in patients with metastatic melanoma.
• Estimate the duration of in vivo persistence of adoptively transferred CD8+ antigen-specific cytotoxic T-cell clones in these patients.
• Evaluate the antitumor effects of CD8+ antigen-specific T-cell clones in these patients.

OUTLINE: Autologous peripheral blood mononuclear cells are harvested and then CD8+ cytotoxic T-lymphocyte (CTL) clones targeting melanosomal antigens are generated ex vivo. Patients receive cellular adoptive immunotherapy comprising autologous CD8+ CTL clones over 30 minutes on day 1. Patients also receive interleukin-2 subcutaneously every 12 hours on days 1-14 of courses 2-3. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed for approximately 1 year after the last infusion.

PROJECTED ACCRUAL: Approximately 20 patients will be accrued for this study.

Enrollment: 20 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histopathologically proven metastatic melanoma

  • No CNS metastases

• HLA-A2 positive

• Bidimensionally measurable disease by palpation on clinical exam or radiographic imaging (x-ray, CT scan, or MRI)

• Surgically accessible site for tumor cell procurement (skin, subcutaneous nodule, or superficial node) and patient clinically eligible for such surgery

PATIENT CHARACTERISTICS:

Age

• 18 to 75

Performance status

• Karnofsky 80-100%

Life expectancy

• More than 16 weeks

Hematopoietic

• WBC greater than 4,000/mm^3
• Absolute neutrophil count greater than 2,000/mm^3
• Platelet count greater than 100,000/mm^3
• Hematocrit greater than 30%

Hepatic

• Bilirubin no greater than 1.6 mg/dL
• SGOT no greater than 150 IU (or no greater than 3 times normal)
• Prothrombin time no greater than 1.5 times control

Renal

• Creatinine no greater than 2.0 mg/dL
• Calcium no greater than 12 mg/dL

Cardiovascular

• No congestive heart failure
• No clinically significant hypotension
• No symptoms of coronary artery disease
• No arrhythmia on EKG requiring drug therapy

Pulmonary

• No severe chronic obstructive pulmonary disease
• FEV_1 at least 1.0 L
• DLCO at least 45% of predicted

Other

• No active infection or oral temperature greater than 38.2 degrees C within 72 hours of study
• No systemic infection requiring chronic maintenance or suppressive therapy
• HIV negative
• No history of seizures
• No retinitis or choroiditis
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use adequate contraception
• Peripheral blood samples available weekly for 4 consecutive weeks

PRIOR CONCURRENT THERAPY:

Biologic therapy

• At least 4 weeks since other prior immunotherapy

Chemotherapy

• 1 or 2 courses of cytoreductive chemotherapy allowed for bulky disease
• At least 4 weeks since prior standard or investigational chemotherapy

Endocrine therapy

• At least 4 weeks since prior steroid therapy

Radiotherapy

• At least 4 weeks since prior radiotherapy

Surgery

• Not specified

Other

• At least 4 weeks since other prior investigational drug therapy and recovered