Exclusion criteria
tumor, bleeding, arrhythmia, non-melanomatous skin carcinoma, toxicities, malignancy, stroke, necrosis, Heart Failure, prostate cancers, allergic reactions, edema, cardiac disease, human T-lymphotropic virus, SRS, angina, infection, pneumonitis, autoimmune or immune-mediated disease, leptomeningeal disease, infectious disease, intercurrent illness
CARCINOMATOUS MENINGITIS, TUMOR, BLEEDING, ARRHYTHMIA, STROKE, ACUTE CORONARY SYNDROME, NECROSIS, HEART FAILURE, HEART, IN SITU CARCINOMA, ALLERGIC REACTION, REVERSIBLE ISCHEMIC NEUROLOGIC DEFICIT, EDEMA, REMISSION, CARDIAC DISEASE, INTERSTITIAL LUNG DISEASE, BUNDLE BRANCH BLOCK, HEPATITIS B, CHRONIC OBSTRUCTIVE PULMONARY DISEASE, MALIGNANCIES, INFECTION, HEPATITIS C, METASTASES, PROSTATE CANCER, PNEUMONITIS, UNCONTROLLED HYPERTENSION, MYOCARDIAL INFARCTION, VIRUS, TRANSIENT ISCHEMIC ATTACK, METASTATIC DISEASE, INFECTIOUS DISEASE, SKIN DISORDERS
Patients who were HLA-A*02:05Patients must not have had a history of allergic reactions attributed to compounds of similar chemical or biologic composition to fludarabine, cyclophosphamide or other agents used in the study. Patients must not have had a history of chronic or recurrent (within the last year before screening) severe autoimmune or immune-mediated disease requiring steroids or other immunosuppressive treatments, including anti-tumor necrosis factor (TNF) agents. Patients must not have had major surgery within 4 weeks before LD; patients should have been fully recovered from any surgical-related toxicities.Patients with a prior history of symptomatic central nervous system (CNS) metastases must have received treatment (that is, stereotactic radiosurgery (SRS), whole-brain radiation therapy (WBRT) or surgery) and been neurologically stable for ≥1 month, not requiring anti-seizure medications and off steroids for ≥14 days before leukapheresis and LD. Patients with asymptomatic CNS metastatic disease without associated edema, shift, requirement for steroids or anti-seizure medications were eligible. If such a patient received SRS or WBRT, a minimum period of 2 weeks would be needed to lapse between the therapy and LD. Patients with leptomeningeal disease or carcinomatous meningitis were not eligible. Patients must not have had any other active malignancy besides the tumor under study within 3 years before screening. Exceptions were adequately treated malignancies not likely to require therapy (for example, completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma). Newly identified prostate cancers found during cytoprostatectomy were permitted. Patients must have been in complete remission from prior malignancy to be eligible to enter the study.Patients must not have had an electrocardiogram (ECG) showing clinically significant abnormality at screening or showing an average corrected QT interval ≥450 ms in males and ≥470 ms in females (≥480 ms for patients with bundle branch block) over three consecutive ECGs. Either Fridericia’s or Bazett’s formula may have been used to correct the QT interval. Patients must not have had uncontrolled intercurrent illness, including, but not limited to, ongoing or active infection; clinically significant cardiac disease defined by New York Heart Association Class of Heart Failure >1; uncontrolled clinically significant arrhythmia in the last 6 months or acute coronary syndrome (angina or myocardial infarction) in the last 6 months; interstitial lung disease (pneumonitis); history of pneumonectomy or chronic obstructive pulmonary disease with at least one exacerbation within 1 year before the screening visit that required treatment with systemic corticosteroids or resulted in hospitalization; pre-existing active skin disorders of Grade ≥2 severity; current uncontrolled hypertension despite optimal medical therapy; or a history of stroke or CNS bleeding, transient ischemic attack or reversible ischemic neurologic deficit within the last 6 months. Patients who, in the opinion of the investigator, were unlikely to fully comply with protocol requirements were ineligible. Patients must not have been pregnant or breastfeeding.Patients must not have had active infection with human immunodeficiency virus (HIV), hepatitis B virus, hepatitis C virus (HCV) or human T-lymphotropic virus (HTLV). Patients with positive serology for HIV were excluded. Patients who were negative for hepatitis B surface antigen but positive for hepatitis B core antibody must have had undetectable hepatitis B DNA and received prophylaxis against viral reactivation. Prophylaxis should have been initiated before LD therapy and continued for 6 months. Patients who were positive for HCV antibody were screened for HCV RNA by any reverse transcription polymerase chain reaction (PCR) or branched DNA assay. If HCV antibody was positive, eligibility was determined based on a negative screening RNA value. Patients with positive serology for HTLV 1 or 2 were excluded. Re-screening for infectious disease markers was not required at baseline (before LD).