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Phase II Study of Metastatic Melanoma With Lymphodepleting Conditioning and Infusion of Anti-MART-1 F5 TCR-Gene-Engineered Lymphocytes
Bu çalışma, metastatik melanom (metastatic melanoma) yani yayılmış cilt kanseri olan hastalarda, hastanın kendi bağışıklık hücrelerinin (lenfositlerin) laboratuvarda gen mühendisliğiyle değiştirilerek tümöre karşı yönlendirildiği bir gen terapisi yaklaşımını incelemektedir. Bu tedavi öncesinde Cyclophosphamide ve Fludarabine ile hazırlık, sonrasında ise Aldesleukin verilmiştir; çalışmaya daha önce yüksek doz IL-2 almış, MART-1 pozitif ve HLA-A*0201 pozitif, 18 yaş ve üzeri hastalar katılabilmiştir. Çalışma Faz 2 aşamasında yürütülmüş ve tamamlanmıştır.
Yukarıdaki özet, resmî kaydın sade dile aktarılmış halidir. Orijinal İngilizce başlık referans için gösterilir.
Kriterler ClinicalTrials.gov kaydından orijinal İngilizce haliyle alınmıştır. Uygunluk kararını yalnızca deneyi yürüten ekip verebilir.
* INCLUSION CRITERIA:
1. Metastatic melanoma with measurable disease
2. Previously received high dose IL-2 (aldesleukin) and have been either non-responders (progressive disease) or have recurred.
3. Positive for MART-1 by immunohistochemistry (IHC)
4. Greater than or equal to 18 years of age.
5. Willing to sign a durable power of attorney
6. Able to understand and sign the Informed Consent Document
7. Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0 or 1.
8. Life expectancy of greater than three months.
9. Patients of both genders must be willing to practice birth control for four months after receiving the preparative regimen.
10. Patients must be human leukocyte antigen (HLA-A)\*0201 positive
11. Serology:
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1. Seronegative for human immunodeficiency virus (HIV) antibody. (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who are HIV seropositive can have decreased immune -competence and thus be less responsive to the experimental treatment and more susceptible to its toxicities.)
2. Seronegative for hepatitis B antigen and hepatitis C antibody unless antigen negative.
3. Women of child-bearing potential must have a negative pregnancy test because of the potentially dangerous effects of the preparative chemotherapy on the fetus.
l. Hematology:
1. Absolute neutrophil count greater than 1000/mm\^3 without the support of filgrastim.
2. White blood cell (WBC) (greater than 3000/mm\^3).
3. Platelet count greater than 100,000/ mm\^3.
4. Hemoglobin greater than 8.0 g/dl.
m. Chemistry:
1. Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) less or equal to 2.5 times the upper limit of normal.
2. Serum creatinine less than or equal to 1.6 mg/dl.
3. Total bilirubin less than or equal to 1.5 mg/dl, except in patients with Gilbert's Syndrome who must have a total bilirubin less than 3.0 mg/dl.
n. More than four weeks must have elapsed since any prior systemic therapy at the time the patient receives the preparative regimen, and patients' toxicities must have recovered to a grade 1 or less (except for toxicities such as alopecia or vitiligo).
o. Six weeks must have elapsed since prior anti-CTLA4 antibody therapy to allow antibody levels to decline.
p. Patients who have previously received anti-CTLA4 antibody must have a normal colonoscopy with normal colonic biopsies.
EXCLUSION CRITERIA:
1. Patients with reactive TIL (IFN-gamma release greater than 200 pg/mL) available based on overnight co-culture assay with autologous tumor or MHC-matched tumor cells.
2. Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant.
3. Active systemic infections, coagulation disorders or other major medical illnesses of the cardiovascular, respiratory or immune system, myocardial infarction, cardiac arrhythmias, obstructive or restrictive pulmonary disease.
4. Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease).
5. Opportunistic infections (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who have decreased immune competence may be less responsive to the experimental treatment and more susceptible to its toxicities).
6. Systemic steroid therapy.
7. History of severe immediate hypersensitivity reaction to any of the agents used in this study.
8. History of coronary revascularization or ischemic symptoms.
9. Any patient known to have an left ventricular ejection fraction (LVEF) less than or equal to 45 percent.
10. Documented LVEF of less than or equal to 45 percent tested in patients with:
* Clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block.
* Age greater than or equal to 60 years old.
11. Documented forced expiratory volume 1 (FEV1) less than or equal to 60 percent predicted tested in patients with:
* A prolonged history of cigarette smoking (20 pk/yrs of smoking).
* Symptoms of respiratory dysfunction.