2020
Phase 1 dose escalation trial of volasertib in combination with decitabine in patients with acute myeloid leukemia
Cortes J, Podoltsev N, Kantarjian H, Borthakur G, Zeidan AM, Stahl M, Taube T, Fagan N, Rajeswari S, Uy GL. Phase 1 dose escalation trial of volasertib in combination with decitabine in patients with acute myeloid leukemia. International Journal Of Hematology 2020, 113: 92-99. PMID: 32951163, DOI: 10.1007/s12185-020-02994-8.Peer-Reviewed Original ResearchMeSH KeywordsAgedAntineoplastic Combined Chemotherapy ProtocolsCell Cycle ProteinsDecitabineDose-Response Relationship, DrugFebrile NeutropeniaFeeding and Eating DisordersFemaleGene ExpressionHumansLeukemia, Myeloid, AcuteMaleMolecular Targeted TherapyProtein Serine-Threonine KinasesProto-Oncogene ProteinsPteridinesTreatment OutcomeConceptsAcute myeloid leukemiaMyeloid leukemiaCommon treatment-emergent adverse eventsPhase 1 dose-escalation trialTreatment-emergent adverse eventsMTD of volasertibObjective response rateAdverse event profileDose-escalation trialPhase 1 trialAnti-leukemic activityPolo-like kinase 1Febrile neutropeniaEscalation trialAdverse eventsCell cycle kinase inhibitorsAML patientsEvent profilePoor prognosisResponse ratePatientsVolasertibDecitabineKinase inhibitorsNumerous cancers
2019
Safety, Efficacy and Biomarker Analysis of a Phase 1b/2 Study of Onvansertib (ONV), a Polo-like Kinase 1 (PLK1) Inhibitor, in Combination with Low-Dose Cytarabine (LDAC) or Decitabine (DEC) in Patients (pts) with Relapsed/Refractory Acute Myeloid Leukemia (R/R AML)
Zeidan A, Schiller G, Lin T, Becker P, Patel P, Wang E, Spira A, Tsai M, Ridinger M, Croucher P, Erlander M, Silberman S. Safety, Efficacy and Biomarker Analysis of a Phase 1b/2 Study of Onvansertib (ONV), a Polo-like Kinase 1 (PLK1) Inhibitor, in Combination with Low-Dose Cytarabine (LDAC) or Decitabine (DEC) in Patients (pts) with Relapsed/Refractory Acute Myeloid Leukemia (R/R AML). Blood 2019, 134: 230. DOI: 10.1182/blood-2019-126262.Peer-Reviewed Original ResearchPositive ptsBiomarker positivityPhase 1bBristol-Myers SquibbSpeakers bureauObjective responseCount recoveryPreliminary efficacyBlood samplesNegative groupRelapsed/Refractory Acute Myeloid LeukemiaADC therapeuticsDay 1Jazz PharmaceuticalsRefractory acute myeloid leukemiaBoehringer IngelheimDaiichi SankyoIncomplete count recoveryPhase 1b/2 studyPreclinical AML modelsSubset of ptsLow-dose cytarabinePredictive gene expression signaturesDose-escalation trialPlatelet count recovery
2018
Preliminary Safety, Pharmacokinetics (PK) and Pharmacodynamic (PD) Analysis of the Polo-like Kinase-1 (PLK1) Inhibitor PCM-075, in Combination with Low-Dose Cytarabine (LDAC) or Decitabine (D) in Patients with Relapsed or Refractory (R/R) Acute Myeloid Leukemia (AML)
Zeidan A, Schiller G, Spira A, Patel P, Tsai M, Ridinger M, Silberman S, Erlander M, Cortes J. Preliminary Safety, Pharmacokinetics (PK) and Pharmacodynamic (PD) Analysis of the Polo-like Kinase-1 (PLK1) Inhibitor PCM-075, in Combination with Low-Dose Cytarabine (LDAC) or Decitabine (D) in Patients with Relapsed or Refractory (R/R) Acute Myeloid Leukemia (AML). Blood 2018, 132: 4043. DOI: 10.1182/blood-2018-99-112590.Peer-Reviewed Original ResearchAcute myeloid leukemiaR AMLPhase 1 trialAdverse eventsPLK1 inhibitionBlast cellsPK profilesNon-hematologic adverse eventsPrevious phase 1 trialRandomized phase 2 studyStandard dose-escalation designRefractory acute myeloid leukemiaBM blast cellsGrade 1 fatigueGrade 1 nauseaPreclinical AML modelsTreatment-related deathsLow-dose cytarabinePhase 2 studySerious adverse eventsSpeakers bureauDose-escalation trialFurther dose escalationPhase 3 studyDose-escalation design