2023
Sabatolimab plus hypomethylating agents in previously untreated patients with higher-risk myelodysplastic syndromes (STIMULUS-MDS1): a randomised, double-blind, placebo-controlled, phase 2 trial
Zeidan A, Ando K, Rauzy O, Turgut M, Wang M, Cairoli R, Hou H, Kwong Y, Arnan M, Meers S, Pullarkat V, Santini V, Malek K, Kiertsman F, Niolat J, Ramos P, Menssen H, Fenaux P, Miyazaki Y, Platzbecker U. Sabatolimab plus hypomethylating agents in previously untreated patients with higher-risk myelodysplastic syndromes (STIMULUS-MDS1): a randomised, double-blind, placebo-controlled, phase 2 trial. The Lancet Haematology 2023, 11: e38-e50. PMID: 38065203, DOI: 10.1016/s2352-3026(23)00333-2.Peer-Reviewed Original ResearchConceptsHigh-risk myelodysplastic syndromeProgression-free survivalComplete response rateMyelodysplastic syndromePlacebo groupPrimary endpointUntreated patientsAdverse eventsComplete responseResponse rateImmune-mediated adverse eventsMedian progression-free survivalRandomised phase 3 trialT-cell immunoglobulin domainFinal data cutoffTreatment-related deathsCommon adverse eventsFull analysis setMucin domain 3Phase 2 studyPhase 2 trialPhase 3 trialLeukaemic stem cellsFebrile neutropeniaData cutoff
2022
A phase 1b study of venetoclax and azacitidine combination in patients with relapsed or refractory myelodysplastic syndromes
Zeidan AM, Borate U, Pollyea DA, Brunner AM, Roncolato F, Garcia JS, Filshie R, Odenike O, Watson AM, Krishnadasan R, Bajel A, Naqvi K, Zha J, Cheng W, Zhou Y, Hoffman D, Harb JG, Potluri J, Garcia‐Manero G. A phase 1b study of venetoclax and azacitidine combination in patients with relapsed or refractory myelodysplastic syndromes. American Journal Of Hematology 2022, 98: 272-281. PMID: 36309981, PMCID: PMC10100228, DOI: 10.1002/ajh.26771.Peer-Reviewed Original ResearchConceptsMedian overall survivalMyelodysplastic syndromeOverall survivalTransfusion independenceHematological improvementTherapy failureHigh-risk myelodysplastic syndromeInternational Working Group criteriaHematological adverse eventsPhase 1b studyRefractory myelodysplastic syndromeStandard of careEfficacy of venetoclaxEffective therapeutic strategyFebrile neutropeniaMarrow CROral venetoclaxComplete remissionAdverse eventsMedian durationAzacitidine treatmentMedian timeMarrow responseMulticenter studyGroup criteriaAML-484 First Results of a Phase II Study (STIMULUS-AML1) Investigating Sabatolimab + Azacitidine + Venetoclax in Patients With Newly Diagnosed Acute Myeloid Leukemia (ND AML)
Zeidan A, Westermann J, Kovacsovics T, Assouline S, Schuh A, Kim H, Macias G, Sanford D, Luskin M, Stein E, Malek K, Lyu J, Stegert M, Esteve J. AML-484 First Results of a Phase II Study (STIMULUS-AML1) Investigating Sabatolimab + Azacitidine + Venetoclax in Patients With Newly Diagnosed Acute Myeloid Leukemia (ND AML). Clinical Lymphoma Myeloma & Leukemia 2022, 22: s255. DOI: 10.1016/s2152-2650(22)01303-9.Peer-Reviewed Original ResearchTreatment-related AEsDose-escalation partDose-limiting toxicityIntensive chemotherapyDosage reductionCohort 2Acute myeloid leukemiaDose interruptionFebrile neutropeniaSerious AEsExpansion cohortStudy patientsTreatment discontinuationAdult patientsDurable responsesNeutrophil countTim-3Agent therapyMyelodysplastic syndromePlatelet countSafety profilePatient outcomesMyeloid leukemiaPatientsDay 1Phase 1 study of anti-CD47 monoclonal antibody CC-90002 in patients with relapsed/refractory acute myeloid leukemia and high-risk myelodysplastic syndromes
Zeidan AM, DeAngelo DJ, Palmer J, Seet CS, Tallman MS, Wei X, Raymon H, Sriraman P, Kopytek S, Bewersdorf JP, Burgess MR, Hege K, Stock W. Phase 1 study of anti-CD47 monoclonal antibody CC-90002 in patients with relapsed/refractory acute myeloid leukemia and high-risk myelodysplastic syndromes. Annals Of Hematology 2022, 101: 557-569. PMID: 34981142, PMCID: PMC9414073, DOI: 10.1007/s00277-021-04734-2.Peer-Reviewed Original ResearchConceptsAnti-drug antibodiesAcute myeloid leukemiaDose-limiting toxicityRefractory acute myeloid leukemiaHigh-risk myelodysplastic syndromeMyelodysplastic syndromeMyeloid leukemiaCommon treatment-emergent adverse eventsTreatment-emergent adverse eventsADA-positive patientsPhase 2 dosePresence/frequencyUnexpected safety findingsPhase 1 studyAnti-CD47 antibodyCD47-SIRPα interactionMacrophage-mediated killingHematological cancer cell linesFebrile neutropeniaMonotherapy activityCancer cell linesPrimary endpointSecondary endpointsAdverse eventsObjective response
2021
Venetoclax and Azacitidine in the Treatment of Patients with Relapsed/Refractory Myelodysplastic Syndrome
Zeidan A, Borate U, Pollyea D, Brunner A, Roncolato F, Garcia J, Filshie R, Odenike O, Watson A, Krishnadasan R, Bajel A, Naqvi K, Zha J, Hogdal L, Zhou Y, Hoffman D, Kye S, Garcia-Manero G. Venetoclax and Azacitidine in the Treatment of Patients with Relapsed/Refractory Myelodysplastic Syndrome. Blood 2021, 138: 537. DOI: 10.1182/blood-2021-145646.Peer-Reviewed Original ResearchClinical Trials CommitteeHigh-risk myelodysplastic syndromeMedian overall survivalAdverse eventsMyelodysplastic syndromeTrials CommitteeOverall survivalMedian timeClinical trialsFebrile neutropeniaPrior therapyComplete remissionTransfusion independenceClinical outcomesBcl-2 inhibitorsMyeloid leukemiaEastern Cooperative Oncology Group performance statusGrade treatment-emergent adverse eventsInternational Working Group 2006 criteriaOverall median progression-free survivalIncomplete blood count recoveryMedian progression-free survivalOral BCL-2 inhibitorTreatment-emergent adverse eventsAllogeneic hematopoietic stem cellsEnasidenib plus azacitidine versus azacitidine alone in patients with newly diagnosed, mutant-IDH2 acute myeloid leukaemia (AG221-AML-005): a single-arm, phase 1b and randomised, phase 2 trial
DiNardo CD, Schuh AC, Stein EM, Montesinos P, Wei AH, de Botton S, Zeidan AM, Fathi AT, Kantarjian HM, Bennett JM, Frattini MG, Martin-Regueira P, Lersch F, Gong J, Hasan M, Vyas P, Döhner H. Enasidenib plus azacitidine versus azacitidine alone in patients with newly diagnosed, mutant-IDH2 acute myeloid leukaemia (AG221-AML-005): a single-arm, phase 1b and randomised, phase 2 trial. The Lancet Oncology 2021, 22: 1597-1608. PMID: 34672961, DOI: 10.1016/s1470-2045(21)00494-0.Peer-Reviewed Original ResearchMeSH KeywordsAgedAminopyridinesAntimetabolites, AntineoplasticAntineoplastic Combined Chemotherapy ProtocolsAzacitidineDrug Administration ScheduleDrug-Related Side Effects and Adverse ReactionsFemaleHumansIsocitrate DehydrogenaseLeukemia, Myeloid, AcuteMaleMutationProgression-Free SurvivalRandom AllocationTreatment OutcomeTriazinesConceptsAcute myeloid leukemiaSerious treatment-related adverse eventsTreatment-related adverse eventsDose-finding portionOverall response rateMyeloid leukemiaAdverse eventsFebrile neutropeniaCombination groupInterim analysisEastern Cooperative Oncology Group performance statusCommon treatment-related grade 3Response rateInteractive web response systemTreatment-related grade 3Phase 1b/2 trialPrespecified interim analysisTreatment-related deathsPhase 2 trialWeb response systemPhase 2Acute myeloid leukemia subtypesPhase 2 portionBristol-Myers SquibbAzacitidine monotherapy
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 cancersEffect of enasidenib (ENA) plus azacitidine (AZA) on complete remission and overall response versus AZA monotherapy in mutant -IDH2 ( mIDH2 ) newly diagnosed acute myeloid leukemia (ND-AML).
Dinardo C, Schuh A, Stein E, Montesinos P, Wei A, De Botton S, Zeidan A, Fathi A, Quek L, Kantarjian H, Frattini M, Lersch F, Gong J, Franovic A, Vyas P, Dohner H. Effect of enasidenib (ENA) plus azacitidine (AZA) on complete remission and overall response versus AZA monotherapy in mutant -IDH2 ( mIDH2 ) newly diagnosed acute myeloid leukemia (ND-AML). Journal Of Clinical Oncology 2020, 38: 7501-7501. DOI: 10.1200/jco.2020.38.15_suppl.7501.Peer-Reviewed Original ResearchOverall response rateDuration of responseGrade 3Randomized phase I/II studyPhase I/II studyResponse rateIDH differentiation syndromePoor-risk cytogeneticsComplete remission rateIntermediate-risk cytogeneticsEvent-free survivalPhase II portionImproved response ratesAcute myeloid leukemiaMost common reasonsMutant IDH2AZA monotherapyDifferentiation syndromeECOG PSFebrile neutropeniaIntensive chemotherapyMedian EFSMedian OSPt ageComplete remission
2019
A Phase I Study of CC-90002, a Monoclonal Antibody Targeting CD47, in Patients with Relapsed and/or Refractory (R/R) Acute Myeloid Leukemia (AML) and High-Risk Myelodysplastic Syndromes (MDS): Final Results
Zeidan A, DeAngelo D, Palmer J, Seet C, Tallman M, Wei X, Li Y, Hock N, Burgess M, Hege K, Stock W. A Phase I Study of CC-90002, a Monoclonal Antibody Targeting CD47, in Patients with Relapsed and/or Refractory (R/R) Acute Myeloid Leukemia (AML) and High-Risk Myelodysplastic Syndromes (MDS): Final Results. Blood 2019, 134: 1320. DOI: 10.1182/blood-2019-125363.Peer-Reviewed Original ResearchTreatment-emergent adverse eventsR AMLHigh-risk myelodysplastic syndromeAnti-drug antibodiesAcute myeloid leukemiaMyelodysplastic syndromeADC therapeuticsJazz PharmaceuticalsDaiichi SankyoCelgene CorporationFebrile neutropeniaDose levelsDevelopment of ADAGrade treatment-emergent adverse eventsSerious treatment-emergent adverse eventsGeneral physical health deteriorationPhase I multicenter studyPrior stem cell transplantRefractory acute myeloid leukemiaRed blood cell transfusionBCR-ABL kinase domainAdvisory CommitteeAnti-CD47 monoclonal antibodyExcess blasts-2Grade 4 sepsisA Phase 1b Study of Glasdegib in Combination with Azacitidine in Patients with Untreated Higher-Risk Myelodysplastic Syndromes, Acute Myeloid Leukemia, and Chronic Myelomonocytic Leukemia
Sekeres M, Schuster M, Joris M, Krauter J, Maertens J, Gyan E, Kovacsovics T, Verma A, Vyas P, Wang E, Wendy W, Zeremski M, Kudla A, Chan G, Zeidan A. A Phase 1b Study of Glasdegib in Combination with Azacitidine in Patients with Untreated Higher-Risk Myelodysplastic Syndromes, Acute Myeloid Leukemia, and Chronic Myelomonocytic Leukemia. Blood 2019, 134: 177. DOI: 10.1182/blood-2019-124050.Peer-Reviewed Original ResearchHigh-risk myelodysplastic syndromeChronic myelomonocytic leukemiaAcute myeloid leukemiaLow-dose cytarabineMedian treatment durationComplete remissionPhase 1b trialIntensive chemotherapyOverall survivalMyelodysplastic syndromePersonal feesAdverse eventsMyelomonocytic leukemiaSpeakers bureauSerious TEAEsFebrile neutropeniaMedian ageMedian timeEuropean LeukemiaNetRisk categoriesMyeloid leukemiaMedian (95% CI) OSMortality rateTreatment durationCR/complete remissionA Phase 1b Study Evaluating the Safety and Efficacy of Venetoclax As Monotherapy or in Combination with Azacitidine for the Treatment of Relapsed/Refractory Myelodysplastic Syndrome
Zeidan A, Pollyea D, Garcia J, Brunner A, Roncolato F, Borate U, Odenike O, Bajel A, Watson A, Götze K, Nolte F, Tan P, Hong W, Dunbar M, Zhou Y, Gressick L, Ainsworth W, Harb J, Salem A, Hayslip J, Swords R, Garcia-Manero G. A Phase 1b Study Evaluating the Safety and Efficacy of Venetoclax As Monotherapy or in Combination with Azacitidine for the Treatment of Relapsed/Refractory Myelodysplastic Syndrome. Blood 2019, 134: 565. DOI: 10.1182/blood-2019-124994.Peer-Reviewed Original ResearchStock/stock optionsTreatment-emergent adverse eventsProgression-free survivalMedian progression-free survivalAbbVie IncOverall survivalFebrile neutropeniaStable diseaseMarrow blastsMyelodysplastic syndromeBcl-2 inhibitorsAstra ZenecaFrequent treatment-emergent adverse eventsInternational Working Group 2006 criteriaSerious treatment-emergent adverse eventsAllogeneic stem cell transplantationAdvisory CommitteeDaiichi SankyoCycles of AZACycles of decitabineECOG performance statusPhase 1b studyPhase 2 dosePredominant grade 3Refractory myelodysplastic syndromePS1023 MUTANT IDH1 INHIBITOR IVOSIDENIB (AG‐120) IN COMBINATION WITH AZACITIDINE FOR NEWLY DIAGNOSED ACUTE MYELOID LEUKEMIA
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, Kantarjian H, Stone R, Lam D, Wang X, Gong J, Kapsalis S, Hickman D, Zhang V, Winkler T, Wu B, Vyas P. PS1023 MUTANT IDH1 INHIBITOR IVOSIDENIB (AG‐120) IN COMBINATION WITH AZACITIDINE FOR NEWLY DIAGNOSED ACUTE MYELOID LEUKEMIA. HemaSphere 2019, 3: 460-461. DOI: 10.1097/01.hs9.0000562388.60660.bc.Peer-Reviewed Original ResearchAcute myeloid leukemiaOverall response rateMorphologic leukemia-free stateComplete remissionAdverse eventsFebrile neutropeniaCR rateMyeloid leukemiaMutant IDH1Isocitrate dehydrogenase 1Double-blind placebo-controlled studyGrade 3/4 adverse eventsRefractory acute myeloid leukemiaBone marrow mononuclear cellsCR/CRhGrade adverse eventsIDH differentiation syndromeIDH1 inhibitor ivosidenibMedian response durationPartial hematologic recoveryPhase 1b studyAbsolute neutrophil countPlacebo-controlled studyTreatment of adultsMarrow mononuclear cellsMutant IDH1 inhibitor ivosidenib (IVO; AG-120) in combination with azacitidine (AZA) for newly diagnosed acute myeloid leukemia (ND AML).
Dinardo C, Stein A, Stein E, Fathi A, Frankfurt O, Schuh A, Martinelli G, Patel P, Raffoux E, Tan P, Zeidan A, de Botton S, Kantarjian H, Stone R, Lam D, Gong J, Zhang V, Winkler T, Wu B, Vyas P. Mutant IDH1 inhibitor ivosidenib (IVO; AG-120) in combination with azacitidine (AZA) for newly diagnosed acute myeloid leukemia (ND AML). Journal Of Clinical Oncology 2019, 37: 7011-7011. DOI: 10.1200/jco.2019.37.15_suppl.7011.Peer-Reviewed Original ResearchAdverse eventsECG QTFebrile neutropeniaDouble-blind placebo-controlled studyGrade 3/4 adverse eventsBone marrow mononuclear cellsCR/CRhGrade adverse eventsIDH differentiation syndromeIDH1 inhibitor ivosidenibMedian response durationNon-intensive therapyPartial hematologic recoveryPhase 1b studyPlacebo-controlled studyAcute myeloid leukemiaMarrow mononuclear cellsAZA monotherapyD1-7Differentiation syndromeData cutoffHematologic recoveryMedian durationMedian timeSafety profile