Treatment of Patients With Metastatic Melanoma by Lymphodepleting Conditioning Followed by Infusion of TCR-Gene Engineered Lymphocytes and Subsequent Fowlpox gp100 Vaccination
Data Collection
Melanoma+8
+ Neoplasms
+ Neoplasms by Histologic Type
Treatment Study
Summary
Study start date: May 1, 2004
Actual date on which the first participant was enrolled.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.
Protocol
This section provides details of the study plan, including how the study is designed and what the study is measuring.61 patients to be enrolled
Total number of participants that the clinical trial aims to recruit.Treatment Study
Eligibility
Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.Any sex
Biological sex of participants that are eligible to enroll.Over 18 Years
Range of ages for which participants are eligible to join.Healthy volunteers not allowed
If individuals who are healthy and do not have the condition being studied can participate.Conditions
Pathology
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
Study Centers
These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.This study has 2 locations
Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
Bethesda, United StatesSee the locationNCI - Surgery Branch
Bethesda, United States