Treatment of Patients With Metastatic Melanoma by Lymphodepleting Conditioning Followed by Infusion of TCR-Gene Engineered Lymphocytes and Subsequent Fowlpox gp100 Vaccination
18 Years
N/A
Both
Melanoma (Skin)
Trial Information
Treatment of Patients With Metastatic Melanoma by Lymphodepleting Conditioning Followed by Infusion of TCR-Gene Engineered Lymphocytes and Subsequent Fowlpox gp100 Vaccination
OBJECTIVES:
Primary
- Determine, preliminarily, any clinical tumor regression in lymphodepleted patients with
metastatic melanoma treated with fowlpox gp100 antigen immunization and antitumor
antigen T-cell receptor (TCR)-engineered tumor infiltrating lymphocytes or CD8+
autologous peripheral blood lymphocytes followed by interleukin-2.
Secondary
- Determine the in vivo survival of TCR gene-engineered cells in patients treated with
this regimen.
OUTLINE: Patients are stratified according to their ability to produce tumor-infiltrating
lymphocytes (TIL) (yes vs no).
Patients receive lymphodepleting chemotherapy comprising cyclophosphamide IV over 1 hour on
days -7 and -6 and fludarabine IV over 30 minutes on days -5 to -1.
- Stratum 1 (TIL): Patients receive TIL retrovirally transduced with gp100 antigen TCR
gene IV over 20-30 minutes on day 0*.
- Stratum 2 (CD8+peripheral blood lymphocytes [PBL]): Patients receive CD8+PBL
retrovirally transduced with gp100 antigen TCR gene IV over 20-30 minutes on day 0*.
NOTE: *Day 0 is 1-4 days after the last dose of fludarabine.
Patients in both strata also receive fowlpox-gp100 vaccine (before TIL/PBL infusion) IV over
1-2 minutes on days 0 and 28 and high-dose interleukin-2 (IL-2) IV over 15 minutes every 8
hours on days 0-4 and days 28-32. Patients also receive G-CSF SC once daily beginning on day
0 and continuing until blood counts recover.
Treatment continues in the absence of disease progression or unacceptable toxicity.
Beginning 6-8 weeks after the last dose of vaccine and high-dose IL-2, patients with stable
or responding disease may receive 1 retreatment course.
Responding patients are followed at 1, 3, 6, and 12 months and then annually thereafter.
PROJECTED ACCRUAL: A total of 61 patients will be accrued for this study.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Diagnosis of melanoma
- Metastatic disease
- Measurable disease
- Refractory to standard therapy, including high-dose interleukin-2 therapy
- HLA-A*0201 positive
- Progressive disease during prior immunization to melanoma antigens OR prior treatment
with anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody (MDX-010)
cellular therapy with or without myeloablation allowed provided toxicity resolved to
≤ grade 2 (except vitiligo) AND patient does not require systemic steroids
- No brain metastases
PATIENT CHARACTERISTICS:
Age
- 18 and over
Performance status
- ECOG 0-1
Life expectancy
- More than 3 months
Hematopoietic
- Absolute neutrophil count > 1,000/mm^3
- Platelet count > 100,000/mm^3
- Hemoglobin > 8.0 g/dL
- Lymphocyte count > 500/mm^3
- WBC > 3,000/mm^3
- No coagulation disorders
Hepatic
- AST and ALT < 3 times upper limit of normal (ULN)
- Bilirubin ≤ 2.0 mg/dL (3.0 mg/dL in patients with Gilbert's syndrome)
- Hepatitis B surface antigen negative
- Hepatitis C antibody negative (unless antigen negative)
Renal
- Creatinine ≤ 1.6 mg/dL
Cardiovascular
- LVEF ≥ 45% by cardiac stress test
- No LVEF < 45% in patients ≥ 50 years of age
- No myocardial infarction
- No cardiac arrhythmias
- No symptomatic cardiac ischemia
- No prior EKG abnormalities
- No other major cardiovascular illness
Pulmonary
- FEV_1 ≥ 60% of predicted AND no obstructive or restrictive pulmonary disease
- No symptoms of respiratory dysfunction
- No other major respiratory illness
Immunologic
- HIV negative
- Epstein-Barr virus positive
- No active systemic infections (including opportunistic infections)
- No form of primary (e.g., autoimmune colitis or Crohn's disease) or secondary
immunodeficiency (due to chemotherapy or radiotherapy)
- No prior severe immediate hypersensitivity reaction to any of the study agents
including eggs
- No other major illness of the immune system
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 4 month after study
participation
- Willing to complete a durable power of attorney (DPA)
PRIOR CONCURRENT THERAPY:
Biologic therapy
- See Disease Characteristics
- More than 6 weeks since prior MDX-010
Chemotherapy
- Not specified
Endocrine therapy
- See Disease Characteristics
- No concurrent systemic steroid therapy
Radiotherapy
- Not specified
Surgery
- Not specified
Other
- More than 4 weeks since other prior systemic therapy and recovered
Type of Study:
Interventional
Study Design:
Masking: Open Label, Primary Purpose: Treatment
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:
040181
NCT ID:
NCT00085462
Start Date:
May 2004
Completion Date:
September 2008
Related Keywords:
- Melanoma (Skin)
- recurrent melanoma
- stage IV melanoma
- Melanoma
Name | Location |
|---|---|
| Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office | Bethesda, Maryland 20892-1182 |
| NCI - Surgery Branch | Bethesda, Maryland 20892-1201 |
