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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

Phase 1/Phase 2
18 Years
Not Enrolling
Melanoma (Skin)

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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



- 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.


- 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.


- 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

- 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


- 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



- 18 and over

Performance status

- ECOG 0-1

Life expectancy

- More than 3 months


- 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


- Bilirubin no greater than 2.0 mg/dL (less than 3.0 mg/dL in patients with Gilbert's

- AST/ALT less than 3 times upper limit of normal

- Hepatitis B surface antigen negative

- Hepatitis C virus negative


- Creatinine no greater than 1.6 mg/dL


- 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


- 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


- 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


- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for 4 months after study

- Must sign a durable power of attorney


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


- Recovered from prior chemotherapy

Endocrine therapy

- No concurrent steroids


- Recovered from prior radiotherapy


- Not specified


- More than 4 weeks since prior systemic therapy

Type of Study:


Study Design:

Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:


Safety Issue:


Principal Investigator

Steven A. Rosenberg, MD, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

NCI - Surgery Branch


United States: Food and Drug Administration

Study ID:




Start Date:

June 2003

Completion Date:

September 2008

Related Keywords:

  • Melanoma (Skin)
  • stage IV melanoma
  • recurrent melanoma
  • Melanoma



Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office Bethesda, Maryland  20892-1182
NCI - Center for Cancer Research Bethesda, Maryland  20892