0000000000222543

AUTHOR

Kapil N. Bhalla

showing 4 related works from this author

Activity of Oral Panobinostat (LBH589) in Patients with Myelofibrosis.

2009

Abstract Abstract 2898 Poster Board II-874 Introduction: Panobinostat (LBH589) is a potent pan-deacetylase inhibitor (DACi) targeting epigenetic and non-epigenetic oncogenic pathways. Panobinostat is currently under clinical investigation in a variety of solid tumors and hematologic malignancies. A Phase IA/II trial evaluating oral panobinostat in patients (pts) with advanced hematologic malignancies is currently ongoing, and encouraging clinical activity has been reported previously in pts with lymphoma, myeloma, or leukemia. Here, preliminary activity of oral panobinostat in pts with myelofibrosis (MF) is described. Patients and methods: Pts with advanced hematologic malignancies were tre…

Oncologymedicine.medical_specialtyCytopeniaChemotherapybusiness.industrymedicine.medical_treatmentImmunologyChronic myelomonocytic leukemiaCell BiologyHematologyHematopoietic stem cell transplantationNeutropeniamedicine.diseaseBiochemistryChemotherapy regimenSurgeryTransplantationchemistry.chemical_compoundchemistryInternal medicinePanobinostatmedicinebusinessBlood
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Phase IA/II Study of Oral LBH589, a Novel Deacetylase Inhibitor (DACi), Administered on 2 Schedules, in Patients with Advanced Hematologic Malignanci…

2007

Abstract LBH589 is a novel cinnamic acid hydroxamate DACi which induces apoptosis in multiple hematologic tumor cell lines in vitro at nanomolar levels. LBH589 has been administered orally, once-a-day, on Monday/Wednesday/Friday, every week (Arm 1) or every other week (Arm 2), in cycles of 28 days, to adult pts with advanced hematologic malignancies. A 3-parameter Bayesian logistic regression model guided dose escalation. To date, 61 pts, median age 67 yrs (range 16–87), 40 male, 21 female, have been enrolled: 33 pts in Arm 1 at dose levels (mg/dose) of 20 (9 pts), 30 (12 pts), 40 (10 pts), and 60 (2 pts); 28 pts in Arm 2 at dose levels (mg/dose) of 30 (7 pts), 45 (12 pts), and 60 (9 pts). …

medicine.medical_specialtybusiness.industryNauseaImmunologyPeripheral edemaCell BiologyHematologyNeutropeniamedicine.diseaseBiochemistryGastroenterologySurgeryEvery other weekInternal medicineVomitingmedicineIn patientmedicine.symptombusinessAdverse effectFebrile neutropeniaBlood
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Phase ia/ii, two-arm, open-label, dose-escalation study of oral panobinostat administered via two dosing schedules in patients with advanced hematolo…

2013

Panobinostat is a potent oral pandeacetylase inhibitor that leads to acetylation of intracellular proteins, inhibits cellular proliferation and induces apoptosis in leukemic cell lines. A phase Ia/II study was designed to determine the maximum-tolerated dose (MTD) of daily panobinostat, administered on two schedules: three times a week every week or every other week on a 28-day treatment cycle in patients with advanced hematologic malignancies. The criteria for hematologic dose-limiting toxicities differed between patients with indications associated with severe cytopenias at baseline (leukemia and myeloid disorders) and those less commonly associated with baseline cytopenias (lymphoma and …

MaleOncologyCancer ResearchIndolesMyeloidhodgkin lymphomahydroxamic acidAdministration Oralresponse criteriaPharmacologyHydroxamic Acidst-cell lymphomaHistoneschemistry.chemical_compoundhemic and lymphatic diseasesAged 80 and overHematologyMiddle AgedLeukemiaTreatment Outcomemedicine.anatomical_structuremyelomaOncologyvorinostatHematologic NeoplasmsFemaleAdultmedicine.medical_specialtypanobinostatrefractory multiple-myelomaMaximum Tolerated DoseAntineoplastic AgentsmyelofibrosisNeutropeniahistone deacetylase inhibitorsmyelodysplastic disordersDrug Administration ScheduleYoung AdultInternal medicinePanobinostatmedicineHumansIn patientAdverse effectMyelofibrosisAgedNeoplasm Staginginternational-working-groupacetylationbusiness.industrymedicine.diseaseLymphomachemistryhistone deacetylasehypoxia-inducible factor-1-alphalbh589business
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A Phase I Study of Intravenous LBH589, a Novel Cinnamic Hydroxamic Acid Analogue Histone Deacetylase Inhibitor, in Patients with Refractory Hematolog…

2006

Abstract Purpose: LBH589 is a novel histone deacetylase inhibitor that inhibits proliferation and induces apoptosis in tumor cell lines. In this phase I study, LBH589 was administered i.v. as a 30-minute infusion on days 1 to 7 of a 21-day cycle. Experimental Design: Fifteen patients (median age, 63 years; range, 42-87 years) with acute myeloid leukemia (13 patients), acute lymphocytic leukemia (1 patient), or myelodysplastic syndrome (1 patient) were treated with LBH589 at the following dose levels (mg/m2): 4.8 (3 patients), 7.2 (3 patients), 9.0 (1 patient), 11.5 (3 patient), and 14.0 (5 patients). The levels of histone acetylation were measured using quantitative flow cytometry and plasm…

AdultCancer ResearchIndolesMaximum Tolerated Dosemedicine.drug_classApoptosisPharmacologyHydroxamic AcidsDrug Administration ScheduleHistonesStructure-Activity Relationshipchemistry.chemical_compoundPredictive Value of TestsPanobinostatAcute lymphocytic leukemiaPanobinostatBiomarkers TumormedicineHumansEnzyme InhibitorsAgedCell ProliferationAged 80 and overDose-Response Relationship Drugbusiness.industryHistone deacetylase inhibitorArea under the curveQTcF ProlongationMyeloid leukemiaMiddle AgedPrecursor Cell Lymphoblastic Leukemia-Lymphomamedicine.diseaseHypokalemiaHistone Deacetylase InhibitorsLeukemiaTreatment OutcomeOncologychemistryCinnamatesLeukemia MyeloidMyelodysplastic SyndromesAcute DiseaseInjections IntravenousImmunologymedicine.symptombusinessFollow-Up StudiesClinical Cancer Research
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