Cyclophosphamide and Fludarabine Followed By Interleukin-2 Gene-Modified Tumor Infiltrating Lymphocytes in Treating Patients With Metastatic Melanoma

NCT00062036 | Completed Phase 1

• 4 other identifiers: 03016203-C-0162NCI-5855CDR0000304438
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 2

Brief Summary

RATIONALE: Drugs used in chemotherapy such as cyclophosphamide and fludarabine use different ways to stop tumor cells from dividing so they stop growing or die. Inserting the gene for interleukin-2 into a person's tumor infiltrating lymphocytes may make the body build an immune response to kill tumor cells. Combining cyclophosphamide and fludarabine with gene-modified tumor cells may kill more cancer cells. PURPOSE: This phase I/II trial is studying the side effects and best dose of gene-modified tumor infiltrating lymphocytes when given together with cyclophosphamide and fludarabine and to see how well they work in patients with metastatic melanoma (phase I is closed to accrual 3/29/06).

Conditions

Melanoma (Skin)

Keywords

stage IV melanoma; recurrent melanoma

Outcome Measures

Primary Outcomes (1)

• Survival

Secondary Outcomes (2)

• Clinical tumor regression

• Toxicity profile

Interventions

aldesleukin BIOLOGICAL

filgrastim BIOLOGICAL

incomplete Freund's adjuvant BIOLOGICAL

interleukin-2 gene BIOLOGICAL

therapeutic tumor infiltrating lymphocytes BIOLOGICAL

cyclophosphamide DRUG

fludarabine phosphate DRUG

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Diagnosis of melanoma * Metastatic disease * Refractory to standard therapy including high-dose interleukin-2 (IL-2) therapy * Evaluable disease * Patients may enroll at the cell infusion stage provided they have tumor available for biopsy OR expandable SBIL-2-transduced tumor infiltrating lymphocytes available * Progressive disease during prior immunization to melanoma antigens or cellular therapy, with or without myeloablation, allowed * Symptomatic CNS lesions allowed provided immediate active treatment for symptomatic lesions has been completed PATIENT CHARACTERISTICS: Age * 18 and over Performance status * ECOG 0-1 Life expectancy * More than 3 months Hematopoietic * Absolute neutrophil count greater than 1,000/mm\^3 * WBC greater than 3,000/mm\^3 * Lymphocyte count greater than 500/mm\^3 * Platelet count greater than 100,000/mm\^3 * Hemoglobin greater than 8.0 g/dL * No coagulation disorder Hepatic * Bilirubin no greater than 2.0 mg/dL (less than 3.0 mg/dL in patients with Gilbert's syndrome) * AST/ALT less than 3 times upper limit of normal * Hepatitis B surface antigen negative * Hepatitis C virus negative Renal * Creatinine no greater than 1.6 mg/dL Cardiovascular * No myocardial infarction * No cardiac arrhythmias * No abnormal stress thallium or comparable test * LVEF \> 45% and normal stress cardiac test in patients with the following criteria: * 50 years old or greater * History of EKG abnormalities, symptoms of cardiac ischemia or arrhythmias * No major cardiovascular illness Pulmonary * No obstructive or restrictive pulmonary disease * No major respiratory illness * FEV\_1 \> 60% predicted in patients with prolonged history of cigarette smoking or symptoms of respiratory dysfunction Immunologic * HIV negative * No prior severe immediate hypersensitivity reaction * No primary or secondary immunodeficiency * No active systemic infection * No concurrent opportunistic infection * No major immune system illness Other * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception during and for 4 months after study therapy * Must sign a durable power of attorney PRIOR CONCURRENT THERAPY: Biologic therapy * See Disease Characteristics * No prior anti-cytotoxic T-lymphocyte antibody-4 antibody (CTLA-4) allowed unless post-MDX010 treatment and colonoscopy with colonic biopsies are normal Chemotherapy * Recovered from prior chemotherapy Endocrine therapy * No concurrent steroids Radiotherapy * Recovered from prior radiotherapy Surgery * Not specified Other * More than 4 weeks since prior systemic therapy

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• National Institutes of Health Clinical Center (CC): lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office

Bethesda, Maryland, 20892-1182, United States

Location

NCI - Center for Cancer Research

Bethesda, Maryland, 20892, United States

Location

MeSH Terms

Conditions

Melanoma

Interventions

aldesleukin; Filgrastim; incomplete Freund's adjuvant; Interleukin-2; Cyclophosphamide; fludarabine phosphate

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Granulocyte Colony-Stimulating Factor; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Interleukins; Lymphokines; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Steven A. Rosenberg, MD, PhD

  NCI - Surgery Branch

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Masking: NONE
• Purpose: TREATMENT
• Sponsor Type: NIH

Study Record Dates

• First Submitted: June 5, 2003
• First Posted: June 6, 2003
• Study Start: June 1, 2003
• Primary Completion: February 1, 2007
• Study Completion: September 1, 2008
• Last Updated: July 2, 2017

Record last verified: 2012-03

Locations

US (2)