Cyclophosphamide, Autologous Lymphocytes, and Aldesleukin in Treating Patients With Metastatic Melanoma

Single Patient Study to Evaluate Cellular Adoptive Immunotherapy Using Autologous Lymphocytes Following Cyclophosphamide Conditioning for a Single Patient With Metastatic Melanoma

RATIONALE: Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Biological therapy, such as cellular adoptive immunotherapy using autologous lymphocytes, may stimulate the immune system in different ways and stop tumor cells from growing. Aldesleukin may stimulate the lymphocytes to kill tumor cells. Giving cyclophosphamide together with autologous lymphocytes and aldesleukin may be an effective treatment for metastatic melanoma.

PURPOSE: This phase I/II trial is studying the side effects of giving cyclophosphamide together with autologous lymphocytes and aldesleukin and to see how well it works in treating patients with metastatic melanoma.

Study Overview

• Status: No longer available
• Conditions: Melanoma (Skin)
• Intervention / Treatment: Drug: cyclophosphamide; Biological: therapeutic autologous lymphocytes; Biological: aldesleukin

Detailed Description

OBJECTIVES:

Primary

• Assess the safety and toxicity of cellular adoptive immunotherapy with autologous tumor-infiltrating lymphocytes (TIL) following cyclophosphamide conditioning and post-infusion aldesleukin (IL-2) in patients with metastatic melanoma.
• Assess the duration of in vivo persistence of adoptively transferred lymphocytes.

Secondary

• Evaluate the antitumor effect of adoptively transferred autologous TIL following cyclophosphamide conditioning and post-infusion IL-2 in these patients.

OUTLINE: Patients receive cyclophosphamide IV on days -3 and -2 and autologous tumor-infiltrating lymphocytes (TIL) IV on day 0. Beginning 6 hours after TIL infusion, patients receive high-dose aldesleukin (IL-2) IV three times daily on days 0-5 (for up to 14 doses) OR low-dose IL-2 subcutaneously twice daily on days 0-14 (for up to 28 doses). Patients may then receive two additional courses of TILs and low-dose IL-2 (with or without cyclophosphamide), if indicated.

After completion of study treatment, patients are followed up periodically.

• Study Type: Expanded Access

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

Inclusion Criteria

• Histopathological documentation of melanoma concurrent with the diagnosis of metastatic disease.
• 18 to 75 years of age and able to tolerate high-dose cyclophosphamide
• Bi-dimensionally measurable disease by palpation on clinical exam, or radiographic imaging (X-ray, CT scan).
• For patients receiving HD-IL-2, normal cardiac stress test within 182 days prior to enrollment is required of all patients over 50 years old or those with an abnormal ECG, any history of cardiac disease, a family history of cardiac disease, hypercholesterolemia or hypertension.

• For leukapheresis, patients must meet the following criteria (any exceptions to this will require prior approval by the Apheresis director and Principal Investigator):

  • Pulse: >45 or < 120
  • Weight: >45 kg
  • Temperature: <38C (<100.4 F)
  • WBC: >3,000
  • HCT: >30%
  • Platelets: >100,000
• ADDITIONAL INCLUSION CRITERIA FOR T CELL INFUSION

Exclusion Criteria

• Significant cardiovascular abnormalities as defined by any one of the following:

  • congestive heart failure,
  • clinically significant hypotension,
  • symptoms of coronary artery disease,
  • presence of cardiac arrhythmias on EKG requiring drug therapy
  • ejection fraction < 50 % (echocardiogram or MUGA)
• Patients with active infections or oral temperature > 38.2 C within 72 hours of study entry or systemic infection requiring chronic maintenance or suppressive therapy.

Study Plan

How is the study designed?

Collaborators and Investigators

• Sponsor: Fred Hutchinson Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Cassian Yee, MD, Fred Hutchinson Cancer Center

Study record dates

Study Major Dates

• Study Start: June 1, 2009
• Primary Completion (Anticipated): October 1, 2010

Study Registration Dates

• First Submitted: October 30, 2009
• First Submitted That Met QC Criteria: October 30, 2009
• First Posted (Estimate): November 1, 2009

Study Record Updates

• Last Update Posted (Estimate): August 6, 2010
• Last Update Submitted That Met QC Criteria: August 4, 2010
• Last Verified: August 1, 2010

More Information

Terms related to this study

• Keywords: 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; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Anti-HIV Agents; Anti-Retroviral Agents; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Aldesleukin; Cyclophosphamide
• Other Study ID Numbers: 2355.00; P30CA015704 (U.S. NIH Grant/Contract); FHCRC-2355.00; IR-6984; CDR0000648071 (Registry Identifier: PDQ)