ASH News Daily 2012 - Monday, December 10, 2012 - (Page B-26)

Page B–26 ® ASH NewS DAily search centered on understanding the mechanisms of lymphomagenesis with the ultimate goal of translating better treatments to lymphoma patients. By using an array of pre-clinical models, Dr. Cerchietti has directly contributed to the development of peptide-mimetics and small molecules to target BCL6, HSP90, in collaboration with the lab of Gabriela Chiosis, PhD, and HDAC and DNMT, in collaboration with the team of John Leonard, MD. These developments have resulted in several ongoing clinical trials. Dr. Cerchietti, who started his T:7” own lab in 2011 at Weill Cornell Medical College, is now assistant professor of medicine in hematology and oncology and the Raymond and Beverly Sackler Scholar. Dr. Cerchietti’s ASH Scholar Award supports his research as he discovers the role of the stress response and HSF1 in the physiology and malignancy of germinal centers. He is extremely honored to receive an ASH Scholar Award as it recognizes his recent research as important contributions to the field and provides him with the funding necessary for establishing a successful independent career. Monday, December 10, 2012 Shunbin Ning, PhD Dr. Ning received his BS and PhD from Wuhan University, China, and went on to complete his postdoctoral fellowship at L i n e b e rg e r Comprehensive Cancer Center at the University of North Carolina (UNC) in 2007. Following his fellowship, Shunbin Ning, PhD he assumed a position as a research associate in the same Center, before transitioning to a research assistant professor in the Department of Microbiology and Immunology at UNC School of Medicine in 2009. Dr. Ning is currently an assistant professor in the Department of Cell Biology and Sylvester Comprehensive Cancer Center at the Miller School of Medicine, University of Miami, where he has also served as assistant professor in the School’s Department of Medicine. Dr. Ning is interested in the interaction between the tumor virus Epstein-Barr virus (EBV/HHV4) and the host innate immune system. EBV, as the first identified human tumor virus, has been established as a paradigm for the study of host-virus interaction. Interferon (IFN) regulatory factors (IRFs), a small family of transcription factors, play important roles in many cellular processes including innate immune responses and oncogenesis. Of special interest, several IRFs, including the three oncogenic IRFs, IRF7, -2, and -4, as well as IRF5, intimately interact with EBV latency, which is associated with a large spectrum of lymphomas and carcinomas. Deciphering the molecular events controlling the interaction between EBV and IRFs will help us understand the role of host IFN immune response in viral oncogenesis and may identify potential targets for immunotherapeutic treatment for virus-associated diseases and cancers. T:9.875” cearly-career areer-developmenT ahemaTologiSTS wardS Scholars «« From Page B-25 College of Medicine in the area of transcriptional regulation and therapeutic targeting in lymphoma. Dr. Cerchietti moved to Weill Cornell Medical College of Cornell University in 2008 as part of the same group. Under the guidance and mentorship of Dr. Melnick, his re- (AUC) ≥0.2% of the human exposure at the recommended dose of 14 mg/m2/week. Drug-related fetal effects consisted of folded retina, rotated limbs, and incomplete sternal ossification. 8.3 Nursing Mothers It is not known whether romidepsin is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from ISTODAX, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother. 8.4 Pediatric Use The safety and effectiveness of ISTODAX in pediatric patients has not been established. 8.5 Geriatric Use Of the approximately 300 patients with CTCL or PTCL in trials, about 25% were > 65 years old. No overall differences in safety or effectiveness were observed between these subjects and younger subjects; however, greater sensitivity of some older individuals cannot be ruled out. 8.6 Hepatic Impairment No dedicated hepatic impairment study for ISTODAX has been conducted. Mild hepatic impairment does not alter pharmacokinetics of romidepsin based on a population pharmacokinetic analysis. Patients with moderate and severe hepatic impairment should be treated with caution [See Clinical Pharmacology (12.3)]. 8.7 Renal Impairment No dedicated renal impairment study for ISTODAX has been conducted. Based upon the population pharmacokinetic analysis, renal impairment is not expected to significantly influence drug exposure. The effect of end-stage renal disease on romidepsin pharmacokinetics has not been studied. Thus, patients with end-stage renal disease should be treated with caution [See Clinical Pharmacology (12.3)]. 10 OVERDOSAGE No specific information is available on the treatment of overdosage of ISTODAX. Toxicities in a single-dose study in rats or dogs, at intravenous romidepsin doses up to 2.2 fold the recommended human dose based on the body surface area, included irregular respiration, irregular heart beat, staggering gait, tremor, and tonic convulsions. In the event of an overdose, it is reasonable to employ the usual supportive measures, e.g., clinical monitoring and supportive therapy, if required. There is no known antidote for ISTODAX and it is not known if ISTODAX is dialyzable. 13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenicity studies have not been performed with romidepsin. Romidepsin was not mutagenic in vitro in the bacterial reverse mutation assay (Ames test) or the mouse lymphoma assay. Romidepsin was not clastogenic in an in vivo rat bone marrow micronucleus assay when tested to the maximum tolerated dose (MTD) of 1 mg/kg in males and 3 mg/kg in females (6 and 18 mg/m2 in males and females, respectively). These doses were up to 1.3-fold the recommended human dose, based on body surface area. Based on non-clinical findings, male and female fertility may be compromised by treatment with ISTODAX. In a 26-week toxicology study, romidepsin administration resulted in testicular degeneration in rats at 0.33 mg/kg/dose (2 mg/m2/dose) following the clinical dosing schedule. This dose resulted in AUC0-inf. values that were approximately 2% the exposure level in patients receiving the recommended dose of 14 mg/m2/dose. A similar effect was seen in mice after 4 weeks of drug administration at higher doses. Seminal vesicle and prostate organ weights were decreased in a separate study in rats after 4 weeks of daily drug administration at 0.1 mg/kg/day (0.6 mg/m2/day), approximately 30% the estimated human daily dose based on body surface area. Romidepsin showed high affinity for binding to estrogen receptors in pharmacology studies. In a 26-week toxicology study in rats, atrophy was seen in the ovary, uterus, vagina and mammary gland of females administered doses as low as 0.1 mg/kg/dose (0.6 mg/m2/dose) following the clinical dosing schedule. This dose resulted in AUC0-inf. values that were 0.3% of those in patients receiving the recommended dose of 14 mg/m2/dose. Maturation arrest of ovarian follicles and decreased weight of ovaries were observed in a separate study in rats after four weeks of daily drug administration at 0.1 mg/kg/day (0.6 mg/m2/day). This dose is approximately 30% the estimated human daily dose based on body surface area. 16 HOW SUPPLIED/STORAGE AND HANDLING Keep out of reach of children. Procedures for proper handling and disposal of anticancer drugs should be considered. Several guidelines on this subject have been published1-4 [See References (15)]. 17 PATIENT COUNSELING INFORMATION See FDA-approved patient labeling. 17.1 Instructions • Nausea and Vomiting Nausea and vomiting are common following treatment with ISTODAX. Prophylactic antiemetics are recommended to be used in all patients. Advise patients to report these symptoms so that appropriate treatment can be instituted [See Adverse Reactions (6)]. • Low Blood Counts Patients should be informed that treatment with ISTODAX can cause low blood counts and that frequent monitoring of hematologic parameters is required. Patients should be instructed to report fever or other signs of infection, significant fatigue, shortness of breath, or bleeding [See Warnings and Precautions (5.1)]. • Infections Patients should be informed that infections may occur during treatment with ISTODAX. Patients should be instructed to report fever, cough, shortness of breath with or without chest pain, burning on urination, flu-like symptoms, muscle aches, or worsening skin problems [See Warnings and Precautions (5.2)]. • Tumor Lysis Syndrome Patients at risk of tumor lysis syndrome (i.e, those with advanced stage disease and/or high tumor burden) should be monitored closely for TLS and appropriate measures taken if symptoms are observed [See Warnings and Precautions (5.4)]. • Use in Pregnancy If pregnancy occurs during treatment with ISTODAX, female patients should be advised to seek immediate medical advice and counseling. [See Warnings and Precautions (5.5)]. • Patients should be instructed to read the patient insert carefully. Manufactured for: Celgene Corporation Summit, NJ 07901 Manufactured by: Ben Venue Laboratories, Inc. Bedford, OH 44146 ISTODAX® is a registered trademark of Celgene Corporation U.S. Patents: 4,977,138; 7,608,280; 7,611,724 ISTBVPI.003/PPI.003 09/11 Sophia Adamia, PhD Dr. Adamia completed her PhD in oncology at the Cross Cancer Institute & University of Alberta, Canada. Her doctoral research findings support the idea that initial genetic changes including mutations related to mRNA splicing of hyaluronan synthase 1 (HAS1) gene, overexpression of which has clinical significance in multiple myeloma (MM), can be either inherited or somatically acquired during the earliest stages »» SCHOLARS Page B-28 Cosmos Communications 718.482.1800 K 20786a1 11.01.11 133 1 js 2 Q1 Q2

Table of Contents for the Digital Edition of ASH News Daily 2012 - Monday, December 10, 2012

ASH News Daily 2012 - Monday, December 10, 2012

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