Cyclophosphamide, Fludarabine, and Total-Body Irradiation Followed By Cellular Adoptive Immunotherapy, Autologous Stem Cell Transplantation, and Interleukin-2 in Treating Patients With Metastatic Melanoma

• Status: Completed
• Trial end date: 2009-01-01
• Target enrollment: 0
• Participant gender: All

Summary

RATIONALE: Drugs used in chemotherapy, such as cyclophosphamide and fludarabine, work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Biological therapies, such as cellular adoptive immunotherapy, work in different ways to stimulate the immune system and stop tumor cells from growing. Autologous stem cell transplant may be able to replace immune cells that were destroyed by chemotherapy and radiation therapy. Interleukin-2 may stimulate a person's lymphocytes to kill tumor cells. Combining chemotherapy, radiation therapy, and biological therapy may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving cyclophosphamide and fludarabine together with radiation therapy followed by cellular adoptive immunotherapy, autologous stem cell transplant, and interleukin-2 works in treating patients with metastatic melanoma.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institutes of Health Clinical Center (CC)
• Collaborator: National Cancer Institute (NCI)
• Treatments: Aldesleukin; Cyclophosphamide; Fludarabine; Fludarabine phosphate; Interleukin-2

Criteria

DISEASE CHARACTERISTICS:

• Diagnosis of metastatic melanoma

• Measurable disease

• Resected or stable brain metastases are allowed

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Eastern Cooperative Oncology Group (ECOG) 0-1

Life expectancy

• At least 3 months

Hematopoietic

• See Immunologic

• Absolute neutrophil count > 1,000/mm^3 (without support of filgrastim [G-CSF])

• Platelet count > 100,000/mm^3

• Hemoglobin ≥ 8 g/dL (transfusion allowed)

• No coagulation disorders

Hepatic

• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 3 times upper limit of normal

• Bilirubin ≤ 2 mg/dL (< 3 mg/dL in patients with Gilbert's syndrome)

• No hepatitis B or C

Renal

• Creatinine ≤ 1.6 mg/dL

Cardiovascular

• Left ventricular ejection fraction (LVEF) ≥ 45% by cardiac stress test*

• No active major cardiovascular illness as evidenced by stress thallium or other comparable test

• No myocardial infarction

• No cardiac arrhythmias NOTE: *For patients ≥ 50 years of age receiving high-dose interleukin-2 (IL-2) OR patients with a history of electrocardiogram (EKG) abnormalities, symptoms of cardiac ischemia, or arrhythmias

Pulmonary

• Forced expiratory volume 1 (FEV_1) ≥ 60% of predicted by pulmonary function test in patients with prolonged history of cigarette smoking or symptoms of respiratory dysfunction*

• No active major respiratory illness

• No obstructive or restrictive pulmonary disease NOTE: *For patients receiving high-dose IL-2 only

Immunologic

• No active major immunologic illness

• No active systemic infections

• No primary or secondary immunodeficiency

• Fully recovered immune competence after prior chemotherapy or radiotherapy as evidenced by both of the following:

• Absolute neutrophil count > 1,000/mm^3

• No opportunistic infections

• Human Immunodeficiency virus (HIV) negative

• Epstein-Barr virus positive

Other

• Not pregnant or nursing

• Fertile patients must use effective contraception during and for 4 months after study treatment

PRIOR CONCURRENT THERAPY:

Biologic therapy

• See Disease Characteristics

Chemotherapy

• At least 6 weeks since prior nitrosourea therapy

• No prior cyclophosphamide and fludarabine as part of a preparative regimen on National Cancer Institute (NCI) Surgery Branch adoptive cell therapy studies unless sufficient numbers of CD34+ stem cells (more than 2 x10^6/kg patient weight) have been obtained prior to the administration of chemotherapy

Endocrine therapy

• No concurrent systemic steroid therapy

Radiotherapy

• Not specified

Surgery

• See Disease Characteristics

• Prior minor surgery within the past 3 weeks allowed if recovered

Other

• Recovered from all prior therapy

• At least 30 days since prior systemic therapy

• No other concurrent experimental agents