Cyclophosphamide and Fludarabine Followed by Vaccine Therapy, Gene-Modified White Blood Cell Infusions, and Aldesleukin in Treating Patients With Metastatic Melanoma

• Status: Completed
• Trial end date: 2010-10-01
• Target enrollment: 0
• Participant gender: All

Summary

RATIONALE: Inserting a laboratory-treated gene into a person's white blood cells may make the body build an immune response to kill tumor cells. Giving cyclophosphamide and fludarabine before a white blood cell infusion may suppress the immune system and allow tumor cells to be killed. Vaccines may make the body build an immune response to kill tumor cells. Aldesleukin may stimulate a person's white blood cells to kill tumor cells. Combining white blood cell infusion with vaccine therapy and aldesleukin may cause a stronger immune response and kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of gene-modified white blood cells when given together with cyclophosphamide, fludarabine, vaccine therapy, and aldesleukin and to see how well it works in treating patients with metastatic melanoma.

• Phase: Phase 1
• 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; Freund's Adjuvant; Vaccines

Criteria

DISEASE CHARACTERISTICS:

• Diagnosis of metastatic melanoma

• HLA-A*0201-positive disease

• Measurable disease

• Refractory to standard therapy, including high-dose aldesleukin therapy

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-1

Life expectancy

• More than 3 months

Hematopoietic

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

• Platelet count > 100,000/mm^3

• Hemoglobin > 8.0 g/dL

• Lymphocyte count > 500/mm^3

• WBC > 3,000/mm^3

• No coagulation disorder

Hepatic

• ALT and AST < 3 times upper limit of normal

• Bilirubin ≤ 2.0 mg/dL (< 3.0 mg/dL for patients with Gilbert's disease)

• Hepatitis B antigen negative

• Hepatitis C antibody negative (unless antigen negative)

Renal

• Creatinine ≤ 1.6 mg/dL

Cardiovascular

• No myocardial infarction

• No cardiac arrhythmias

• No cardiac ischemia

• LVEF ≥ 45% by stress cardiac test* (for patients ≥ 50 years of age OR those with a history of EKG abnormalities)

• No other major cardiovascular illness by stress thallium or comparable test NOTE:

*Stress thallium, stress MUGA, dobutamine echocardiogram, or other stress test

Pulmonary

• No major respiratory illness

• No obstructive or restrictive pulmonary disease

• FEV_1 ≥ 60% of predicted on pulmonary function test*

• DLCO ≥ 60% predicted (for total-body irradiation cohort) NOTE: *For patients with a prolonged history of cigarette smoking or symptoms of respiratory dysfunction

Immunologic

• HIV negative

• No major immune system illness

• No active systemic infection or opportunistic infection

• No primary immunodeficiency (e.g., autoimmune colitis or Crohn's disease)

• No secondary immunodeficiency (e.g., due to chemotherapy or radiotherapy)

• No history of severe immediate hypersensitivity reaction to study drugs

Other

• Not pregnant or nursing

• Negative pregnancy test

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

• Must sign a durable power of attorney

PRIOR CONCURRENT THERAPY:

Biologic therapy

• See Disease Characteristics

• Recovered from prior immunotherapy

• Prior immunization to melanoma antigens allowed

• Progressive disease during prior immunization allowed

• Prior cellular therapy, including vector transduction with or without myeloablation, allowed

• More than 6 weeks since prior anticytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) monoclonal antibody (MDX-010) therapy

• No prior anti-CTLA-4 antibody unless a post anti-CTLA-4 antibody treatment colonoscopy was normal by biopsy

Chemotherapy

• Recovered from prior chemotherapy

Endocrine therapy

• No concurrent systemic steroids

Radiotherapy

• Recovered from prior radiotherapy

• No prior significant mediastinal or lung radiation (for total-body irradiation cohort)

Surgery

• Not specified

Other

• More than 4 weeks since prior systemic therapy and recovered