Biological Therapy in Treating Patients With Metastatic Melanoma

Phase I Study to Evaluate the Safety of Cellular Adoptive Immunotherapy Using Autologous CD8+ Antigen Specific T Cell Clones Targeting Cancer Testis Antigens for Patients With Metastatic Melanoma

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.

Study Overview

• Status: Completed
• Conditions: Melanoma (Skin)
• Intervention / Treatment: Biological: aldesleukin; Biological: therapeutic tumor infiltrating lymphocytes

Detailed 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.

• Study Type: Interventional
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Washington
    • Seattle, Washington, United States, 98109-1024
      • Fred Hutchinson Cancer Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

• At least 3 weeks since prior standard or experimental chemotherapy
• 1-2 courses of prior cytoreductive chemotherapy for bulky disease allowed

Endocrine therapy

• No concurrent systemic steroids (except for toxicity management)

Radiotherapy

• At least 3 weeks since prior radiotherapy

Surgery

• Not specified

Other

• At least 3 weeks since prior immunosuppressive therapy
• No concurrent pentoxifylline
• No other concurrent investigational agents

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Masking: None (Open Label)

Collaborators and Investigators

• Sponsor: Fred Hutchinson Cancer Center
• Collaborators: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start: October 1, 2002
• Study Completion (Actual): June 1, 2005

Study Registration Dates

• First Submitted: September 6, 2002
• First Submitted That Met QC Criteria: May 27, 2003
• First Posted (Estimate): May 28, 2003

Study Record Updates

• Last Update Posted (Estimate): May 7, 2010
• Last Update Submitted That Met QC Criteria: May 5, 2010
• Last Verified: May 1, 2010

More Information

Terms related to this study

• Keywords: recurrent melanoma; stage IV melanoma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma; Anti-Infective Agents; Antiviral Agents; Anti-HIV Agents; Anti-Retroviral Agents; Antineoplastic Agents; Aldesleukin
• Other Study ID Numbers: 1588.00; FHCRC-1588.00; NCI-H02-0091; CDR0000256451 (Registry Identifier: PDQ)