2020
Clinical Efficacy and Safety of Oral Decitabine/Cedazuridine in 133 Patients with Myelodysplastic Syndromes (MDS) and Chronic Myelomonocytic Leukemia (CMML)
Savona M, McCloskey J, Griffiths E, Yee K, Al-Kali A, Zeidan A, Deeg H, Patel P, Sabloff M, Keating M, Dao K, Zhu N, Gabrail N, Fazal S, Maly J, Odenike O, Kantarjian H, DeZern A, O'Connell C, Roboz G, Busque L, Wells R, Amin H, Randhawa J, Leber B, Hao Y, Keer H, Azab M, Garcia-Manero G. Clinical Efficacy and Safety of Oral Decitabine/Cedazuridine in 133 Patients with Myelodysplastic Syndromes (MDS) and Chronic Myelomonocytic Leukemia (CMML). Blood 2020, 136: 37-38. PMCID: PMC8330281, DOI: 10.1182/blood-2020-133855.Peer-Reviewed Original ResearchChronic myelomonocytic leukemiaRed blood cellsMyelodysplastic syndromeComplete responseHematological improvementAdverse eventsAstex PharmaceuticalsHypomethylating agentConsecutive weeksSpeakers bureauMedian durationClinical efficacyDaiichi SankyoDNA methyltransferase inhibitorCommon treatment-emergent adverse eventsAllogeneic hematopoietic cell transplantTreatment-emergent adverse eventsTreatment of MDSBoehringer IngelheimAdvisory CommitteeRandomized cross-over studySeattle GeneticsDose combination drugsOral hypomethylating agentOverall objective responseMolecular Characterization of Clinical Response and Relapse in Patients with IDH1-Mutant Newly Diagnosed Acute Myeloid Leukemia Treated with Ivosidenib and Azacitidine
Daigle S, Choe S, DiNardo C, Stein A, Stein E, Fathi A, Frankfurt O, Schuh A, Döhner H, Martinelli G, Patel P, Raffoux E, Tan P, Zeidan A, De Botton S, Stone R, Frattini M, Franovic A, Xu E, Winkler T, Wu B, Vyas P. Molecular Characterization of Clinical Response and Relapse in Patients with IDH1-Mutant Newly Diagnosed Acute Myeloid Leukemia Treated with Ivosidenib and Azacitidine. Blood 2020, 136: 49-51. DOI: 10.1182/blood-2020-136922.Peer-Reviewed Original ResearchPeripheral blood mononuclear cellsAcute myeloid leukemiaBone marrow mononuclear cellsCurrent equity holderIntensive induction chemotherapyAgios PharmaceuticalsSafety monitoring boardIsocitrate dehydrogenase 1Daiichi SankyoSeattle GeneticsSpeakers bureauBristol-Myers SquibbIDH2 mutationsPTC TherapeuticsClinical responseMononuclear cellsClinical trialsDisease progressionMyeloid leukemiaMonitoring boardRefractory (R/R) AMLMutant IDH1R AMLAdvisory CommitteeForty-seven
2019
Pharmacokinetic Exposure Equivalence and Preliminary Efficacy and Safety from a Randomized Cross over Phase 3 Study (ASCERTAIN study) of an Oral Hypomethylating Agent ASTX727 (cedazuridine/decitabine) Compared to IV Decitabine
Garcia-Manero G, McCloskey J, Griffiths E, Yee K, Zeidan A, Al-Kali A, Dao K, Deeg H, Patel P, Sabloff M, Keating M, Zhu N, Gabrail N, Fazal S, Maly J, Odenike O, Shastri A, DeZern A, O'Connell C, Roboz G, Oganesian A, Hao Y, Keer H, Azab M, Savona M. Pharmacokinetic Exposure Equivalence and Preliminary Efficacy and Safety from a Randomized Cross over Phase 3 Study (ASCERTAIN study) of an Oral Hypomethylating Agent ASTX727 (cedazuridine/decitabine) Compared to IV Decitabine. Blood 2019, 134: 846. DOI: 10.1182/blood-2019-122980.Peer-Reviewed Original ResearchPhase 3 studyFixed-dose combinationClinical trialsHematologic improvementAdverse eventsAstex PharmaceuticalsSpeakers bureauIncyte CorporationSafety findingsComplete responseRandomized crossOtsuka PharmaceuticalClinical activityHypomethylating agentOral fixed-dose combinationCelgene CorporationRandomized phase 3 studyBoehringer IngelheimAdvisory CommitteeSeattle GeneticsDaiichi SankyoClinic visit frequencyComparable clinical activityDifferent myeloid malignanciesPlatelet transfusion dependenceEnasidenib Plus Azacitidine Significantly Improves Complete Remission and Overall Response Compared with Azacitidine Alone in Patients with Newly Diagnosed Acute Myeloid Leukemia (AML) with Isocitrate Dehydrogenase 2 (IDH2) Mutations: Interim Phase II Results from an Ongoing, Randomized Study
DiNardo C, Schuh A, Stein E, Fernandez P, Wei A, De Botton S, Zeidan A, Fathi A, Quek L, Kantarjian H, Frattini M, Lersch F, Gong J, Franovic A, MacBeth K, Vyas P, Döhner H. Enasidenib Plus Azacitidine Significantly Improves Complete Remission and Overall Response Compared with Azacitidine Alone in Patients with Newly Diagnosed Acute Myeloid Leukemia (AML) with Isocitrate Dehydrogenase 2 (IDH2) Mutations: Interim Phase II Results from an Ongoing, Randomized Study. Blood 2019, 134: 643. DOI: 10.1182/blood-2019-130362.Peer-Reviewed Original ResearchOverall response rateAcute myeloid leukemiaDuration of responseMorphologic leukemia-free stateBone marrow mononuclear cellsAZA armComplete remissionIntensive chemotherapyCelgene CorporationResponse rateDaiichi SankyoVariant allele frequencySpeakers bureauPTC TherapeuticsPartial remissionData cutoffGrade 3Phase I/II studyMedian DORAdvisory CommitteeSeattle GeneticsForty-sevenConventional care regimensIDH differentiation syndromePoor-risk cytogeneticsClinical Benefit of Glasdegib in Combination with Azacitidine or Low-Dose Cytarabine in Patients with Acute Myeloid Leukemia
Zeidan A, Schuster M, Krauter J, Maertens J, Gyan E, Joris M, Menne T, Vyas P, Wendy W, O'Connell A, Zeremski M, Kudla A, Chan G, Sekeres M. Clinical Benefit of Glasdegib in Combination with Azacitidine or Low-Dose Cytarabine in Patients with Acute Myeloid Leukemia. Blood 2019, 134: 3916. DOI: 10.1182/blood-2019-124034.Peer-Reviewed Original ResearchTreatment-emergent adverse eventsAcute myeloid leukemiaLow-dose cytarabineMedian treatment durationIntensive chemotherapyOverall survivalPersonal feesMyelodysplastic syndromeDose delaysSpeakers bureauMedian followMyeloid leukemiaTreatment durationSerious treatment-emergent adverse eventsRandomized phase 3 trialMonths median overall survivalNon-financial supportAdvisory CommitteeSeattle GeneticsDaiichi SankyoIncomplete hematologic recoveryOlder unfit patientsMedian overall survivalSuperior overall survivalAbsolute neutrophil countPharmacodynamic Responses to CC-90009, a Novel Cereblon E3 Ligase Modulator, in a Phase I Dose-Escalation Study in Relapsed or Refractory Acute Myeloid Leukemia (R/R AML)
Fan J, Wang H, Couto S, Yao T, Uy G, Zeidan A, Minden M, Montesinos P, DeAngelo D, Altman J, Koprivnikar J, Vyas P, Fløisand Y, Vidriales M, Gjertsen B, Buchholz T, Pourdehnad M, Pierce D. Pharmacodynamic Responses to CC-90009, a Novel Cereblon E3 Ligase Modulator, in a Phase I Dose-Escalation Study in Relapsed or Refractory Acute Myeloid Leukemia (R/R AML). Blood 2019, 134: 2547. DOI: 10.1182/blood-2019-124291.Peer-Reviewed Original ResearchNovel cereblon E3 ligase modulatorCereblon E3 ligase modulatorPeripheral blood mononuclear cellsCC-90009T cellsPharmacodynamic responseCelgene CorporationDaiichi SankyoSpeakers bureauR AMLAML blastsIntegrated stress responseBlast cellsDay 1Dose levelsPhase I dose-escalation studyRefractory acute myeloid leukemiaI dose-escalation studyAdvisory CommitteeBone marrow core biopsiesAntileukemic activitySeattle GeneticsPhase IHigh-dose cohortNorwegian Cancer Society