Tumor Infiltrating Lymphocytes (TIL Cells) Transduced With An Interleukin-2 (SBIL-2) Gene Following The Administration Of A Nonmyeloablative But Lymphocyte Depleting Regimen in Metastatic Melanoma
18 Years
N/A
Both
Melanoma (Skin)
Trial Information
Tumor Infiltrating Lymphocytes (TIL Cells) Transduced With An Interleukin-2 (SBIL-2) Gene Following The Administration Of A Nonmyeloablative But Lymphocyte Depleting Regimen in Metastatic Melanoma
OBJECTIVES:
Primary
- Determine the survival of patients with metastatic melanoma administered interleukin-2
gene-modified tumor infiltrating lymphocytes after cyclophosphamide and fludarabine.
- Compare survival results with prior Surgery Branch studies using adoptive cell therapy
without the interleukin-2 retroviral vector (SBIL-2) gene.
Secondary
- Determine clinical tumor regression in patients administered interleukin-2
gene-modified TIL after cyclophosphamide and fludarabine followed by interleukin-2.
- Determine the toxicity profile of this regimen in these patients.
OUTLINE:
- Phase I (closed to accrual as of 3/29/06):
- Harvest: TIL are harvested, transduced with IL-2 gene, and expanded in vitro over
a period of approximately 4 weeks.
- Nonmyeloablative preparative regimen (chemotherapy): Patients receive
cyclophosphamide IV over 1 hour on days -7 and -6 and fludarabine IV over 30
minutes on days -5 to -1.
- Lymphocyte administration: Patients receive IL-2 gene-transduced TIL IV over 20-30
minutes on day 0. They also receive high-dose IL-2 IV over 15 minutes every 8
hours on days 0 -5 (maximum 15 doses). Beginning 1-2 days after lymphocyte
administration, patients receive filgrastim (G-CSF) subcutaneously (SC) daily, ,
until blood counts recover.
- Retreatment: Patients are re-evaluated every 4-6 weeks. Retreatment depends on
disease status after each regimen. Patients with dose-limiting toxicity do not
receive further treatment.
- No response: Patients with stable disease or disease progression after the
initial treatment are followed or removed from the study.
- Partial response: Patients with a partial or minor response after the initial
treatment may receive retreatment, approximately 2-4 weeks later, with
chemotherapy, IL-2 gene-transduced TIL, immunization, and high-dose IL-2 as
above, every 4-6 weeks for up to 2 courses provided at least a partial
response is documented after each regimen.
- Complete response: Patients with a complete response receive no further
treatment.
- Phase II: Patients receive treatment and retreatment as in phase I with the MTD of IL-2
gene-transduced TIL.
Patients are followed every 3-6 weeks in the absence disease progression.
PROJECTED ACCRUAL: A total of 33 patients will be accrued for this study.
Inclusion Criteria
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
Type of Study:
Interventional
Study Design:
Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Survival
Safety Issue:
No
Principal Investigator
Steven A. Rosenberg, MD, PhD
Investigator Role:
Principal Investigator
Investigator Affiliation:
NCI - Surgery Branch
Authority:
United States: Food and Drug Administration
Study ID:
030162
NCT ID:
NCT00062036
Start Date:
June 2003
Completion Date:
September 2008
Related Keywords:
- Melanoma (Skin)
- stage IV melanoma
- recurrent melanoma
- Melanoma
Name | Location |
|---|---|
| Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office | Bethesda, Maryland 20892-1182 |
| NCI - Center for Cancer Research | Bethesda, Maryland 20892 |
