2024
Phase I Study of Ruxolitinib in Combination with Abemaciclib for Patients with Primary or Post-Polycythemia Vera/Essential Thrombocythemia Myelofibrosis
Bewersdorf J, Derkach A, Zeidan A, Stein E, Mauro M, Podoltsev N, Rampal R. Phase I Study of Ruxolitinib in Combination with Abemaciclib for Patients with Primary or Post-Polycythemia Vera/Essential Thrombocythemia Myelofibrosis. Blood 2024, 144: 6659-6659. DOI: 10.1182/blood-2024-194918.Peer-Reviewed Original ResearchDose-limiting toxicityCancer Institute Common Terminology Criteria for Adverse EventsTreatment-related adverse eventsAdverse eventsDose levelsCombination therapySpleen volumeInhibitor abemaciclibGrade 3Patients discontinued treatment due to adverse eventsNational Cancer Institute Common Terminology Criteria for Adverse EventsPhase I dose-escalation trialTreatment due to adverse eventsCommon Terminology Criteria for Adverse EventsDisease progressionRecommended phase II doseMulticenter Phase IPlanned dose levelsGrade 3 thrombocytopeniaMedian overall survivalPhase II doseBone marrow blastsBone marrow fibrosisClinically significant bleedingData cut-offZiftomenib Combined with Intensive Induction (7+3) in Newly Diagnosed NPM1- m or KMT2A -r Acute Myeloid Leukemia: Interim Phase 1a Results from KOMET-007
Zeidan A, Wang E, Issa G, Erba H, Altman J, Balasubramanian S, Strickland S, Roboz G, Schiller G, McMahon C, Palmisiano N, Madanat Y, Rotta M, Nadiminti K, Wei H, Riches M, Corum D, Leoni M, Dale S, Fathi A. Ziftomenib Combined with Intensive Induction (7+3) in Newly Diagnosed NPM1- m or KMT2A -r Acute Myeloid Leukemia: Interim Phase 1a Results from KOMET-007. Blood 2024, 144: 214-214. DOI: 10.1182/blood-2024-198218.Peer-Reviewed Original ResearchDose-limiting toxicityMinimal residual diseaseAcute myeloid leukemiaMedian time to neutrophil recoveryDays to platelet recoveryMinimal residual disease negativityDecreased neutrophil countKMT2A-rDecreased platelet countNPM1 mutationsAdverse eventsCRC ratesDose levelsNeutrophil recoveryData cutoffQTc prolongationPlatelet recoveryPlatelet countMyeloid leukemiaNeutrophil countDifferentiation syndromeClinical activityCycle 1 day 8Persistent acute myeloid leukemiaStandard dose of cytarabineA Phase 2B, Open-Label Multicenter Study of Tebapivat (AG-946), a Potent Pyruvate Kinase Activator, in Patients with Anemia Due to Lower-Risk Myelodysplastic Syndromes
Zeidan A, Sekeres M, Al-Samkari H, Carraway H, DeZern A, Mittelman M, Little M, Beynon V, Dai X, Sommakia S, Despotovic J, Patel P, Dibacco M, Fattizzo B, Stein E, Sallman D, Kulasekararaj A, Platzbecker U, Fenaux P. A Phase 2B, Open-Label Multicenter Study of Tebapivat (AG-946), a Potent Pyruvate Kinase Activator, in Patients with Anemia Due to Lower-Risk Myelodysplastic Syndromes. Blood 2024, 144: 6708-6708. DOI: 10.1182/blood-2024-203073.Peer-Reviewed Original ResearchLower-risk MDSErythropoiesis-stimulating agentsLower-risk myelodysplastic syndromesRed blood cell unitsMyelodysplastic syndromeProportion of patientsDose levelsRed blood cellsIPSS-RTransfusion burdenOpen-labelFirst doseRevised International Prognostic Scoring SystemHistory of acute myeloid leukemiaMDS mouse modelsMedian duration of responsePhase 2bInternational Prognostic Scoring SystemOpen-label multicenter studyAssociated with increased morbidityBone marrow neoplasmsHigh transfusion burdenIPSS-R scoreLow transfusion burdenDose level 1
2023
Encouraging Efficacy Observed in Bexmab Study: A Phase 1/2 Study to Assess Safety and Efficacy of Bexmarilimab in Combination with Standard of Care in Myeloid Malignancies
Kontro M, Stein A, Pyörälä M, Rimpiläinen J, Siitonen T, Hollmén M, Fjaellskog M, Pawlitzky I, Zeidan A, Daver N. Encouraging Efficacy Observed in Bexmab Study: A Phase 1/2 Study to Assess Safety and Efficacy of Bexmarilimab in Combination with Standard of Care in Myeloid Malignancies. Blood 2023, 142: 2915. DOI: 10.1182/blood-2023-174912.Peer-Reviewed Original ResearchAcute myeloid leukemiaR AMLCLEVER-1Complete remissionStandard of careBex treatmentAdverse eventsBone marrow cellsHMA failureMarrow CRPatient BMPrior therapyPartial remissionAML patientsMedian numberT cellsDose levelsMyeloid malignanciesHigh-risk MDS patientsMarrow cellsMarrow complete remissionR AML patientsRisk MDS patientsNK cell numbersPhase 1/2 studyA First-in-Human, Phase 1, Dose Escalation Study of Sgr-2921 As Monotherapy in Subjects with Relapsed/Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome
DiNardo C, Strickland S, Skikne B, Zeidan A, Traer E, Carraway H, Frankel S, Weiss D, Wang J, Pirie-Shepherd S, Piccotti J, Wright D, Akinsanya K. A First-in-Human, Phase 1, Dose Escalation Study of Sgr-2921 As Monotherapy in Subjects with Relapsed/Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome. Blood 2023, 142: 1548. DOI: 10.1182/blood-2023-186036.Peer-Reviewed Original ResearchR AMLAcute myeloid leukemiaRefractory acute myeloid leukemiaCell line-derived xenograftsDose-escalation studyMyelodysplastic syndromeCentral nervous systemDose levelsEscalation studyFirst doseTreatment armsMyeloid leukemiaEastern Cooperative Oncology Group performance statusRelapsed/Refractory Acute Myeloid LeukemiaPatient-derived xenograft AML modelHigh-risk myelodysplastic syndromeHigh unmet medical needAnimal models representativeMultiple prior linesPhase 2 doseSingle-patient cohortsTreatment arm ATreatment arm B.Antitumor activitySingle-dose pharmacokinetics
2020
MDS-175: Assessment of Dose-Dependent Response to Luspatercept in Patients with Lower-Risk Myelodysplastic Syndromes (LR-MDS) with Ring Sideroblasts (RS) in the Phase 3 MEDALIST Trial
Platzbecker U, Fenaux P, Mufti G, Garcia-Manero G, Komrokji R, Buckstein R, Diez-Campelo M, Finelli C, Sekeres M, Selleslag D, DeZern A, Quesnel B, Beyne-Rauzy O, Voso M, Greenberg P, Zeidan A, Adès L, Verma A, Savona M, Laadem A, Ito R, Zhang J, Rampersad A, Morison J, Louis C, Linde P, Santini V. MDS-175: Assessment of Dose-Dependent Response to Luspatercept in Patients with Lower-Risk Myelodysplastic Syndromes (LR-MDS) with Ring Sideroblasts (RS) in the Phase 3 MEDALIST Trial. Clinical Lymphoma Myeloma & Leukemia 2020, 20: s318. DOI: 10.1016/s2152-2650(20)30972-1.Peer-Reviewed Original ResearchTreatment-emergent adverse eventsLower-risk myelodysplastic syndromesRBC-TIRing sideroblastsDose levelsDose reductions/delaysMaximum doseLR-MDS patientsRBC transfusion independenceMajority of patientsMaintenance of responseSame dose levelFirst responseDose delaysDose-dependent responseEligible patientsDose titrationNew onsetTransfusion burdenTransfusion independenceAdverse eventsDose escalationMedian timeMyelodysplastic syndromeHemoglobin increase
2019
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)
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 SocietyA 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 sepsisAssessment of Longer-Term Efficacy and Safety in the Phase 3, Randomized, Double-Blind, Placebo-Controlled MEDALIST Trial of Luspatercept to Treat Anemia in Patients (Pts) with Revised International Prognostic Scoring System (IPSS-R) Very Low-, Low-, or Intermediate-Risk Myelodysplastic Syndromes (MDS) with Ring Sideroblasts (RS) Who Require Red Blood Cell (RBC) Transfusions
Fenaux P, Mufti G, Buckstein R, Santini V, Díez-Campelo M, Finelli C, Cazzola M, Ilhan O, Sekeres M, Komrokji R, List A, Zeidan A, Verma A, Laadem A, Ito R, Zhang J, Rampersad A, Sinsimer D, Linde P, Garcia-Manero G, Platzbecker U. Assessment of Longer-Term Efficacy and Safety in the Phase 3, Randomized, Double-Blind, Placebo-Controlled MEDALIST Trial of Luspatercept to Treat Anemia in Patients (Pts) with Revised International Prognostic Scoring System (IPSS-R) Very Low-, Low-, or Intermediate-Risk Myelodysplastic Syndromes (MDS) with Ring Sideroblasts (RS) Who Require Red Blood Cell (RBC) Transfusions. Blood 2019, 134: 841. DOI: 10.1182/blood-2019-123064.Peer-Reviewed Original ResearchErythropoiesis-stimulating agentsIntermediate-risk myelodysplastic syndromesRBC-TIClinical benefitMyelodysplastic syndromeData cutoffHighest dose levelTransfusion burdenCelgene CorporationRing sideroblastsSpeakers bureauMedian durationDose levelsInternational Working Group 2006 criteriaClass erythroid maturation agentGrade 1Red blood cell transfusionInternational Prognostic Scoring SystemLower-risk myelodysplastic syndromesAdvisory CommitteeLow-risk MDSRBC transfusion independenceRegular RBC transfusionsMedian treatment durationBlood cell transfusionClinical Activity of CC-90009, a Cereblon E3 Ligase Modulator and First-in-Class GSPT1 Degrader, As a Single Agent in Patients with Relapsed or Refractory Acute Myeloid Leukemia (R/R AML): First Results from a Phase I Dose-Finding Study
Uy G, Minden M, Montesinos P, DeAngelo D, Altman J, Koprivnikar J, Vyas P, Fløisand Y, Vidriales M, Gjertsen B, Esteve J, Buchholz T, Couto S, Fan J, Hanna B, Li L, Pierce D, Hege K, Pourdehnad M, Zeidan A. Clinical Activity of CC-90009, a Cereblon E3 Ligase Modulator and First-in-Class GSPT1 Degrader, As a Single Agent in Patients with Relapsed or Refractory Acute Myeloid Leukemia (R/R AML): First Results from a Phase I Dose-Finding Study. Blood 2019, 134: 232. DOI: 10.1182/blood-2019-123966.Peer-Reviewed Original ResearchTreatment-emergent adverse eventsCereblon E3 ligase modulatorSystemic inflammatory response syndromeCC-90009Phase 1 studyR AMLHighest dose levelDose levelsCelgene CorporationDaiichi SankyoSpeakers bureauGrade 3/4 treatment-emergent adverse eventsDay 1Jazz PharmaceuticalsObserved treatment-emergent adverse eventOpen-label phase 1 studySerious treatment-emergent adverse eventsHyperglycemic hyperosmolar nonketotic syndromeIncomplete blood count recoveryMorphologic leukemia-free stateRefractory acute myeloid leukemiaHigh-risk myelodysplastic syndromeAdvisory CommitteeAntileukemic activityI Dose-Finding Study
2018
A Multi-center Phase I Trial of Ipilimumab in Patients with Myelodysplastic Syndromes following Hypomethylating Agent Failure
Zeidan AM, Knaus HA, Robinson TM, Towlerton AMH, Warren EH, Zeidner JF, Blackford AL, Duffield AS, Rizzieri D, Frattini MG, Levy YM, Schroeder MA, Ferguson A, Sheldon KE, DeZern AE, Gojo I, Gore SD, Streicher H, Luznik L, Smith BD. A Multi-center Phase I Trial of Ipilimumab in Patients with Myelodysplastic Syndromes following Hypomethylating Agent Failure. Clinical Cancer Research 2018, 24: 3519-3527. PMID: 29716921, PMCID: PMC6680246, DOI: 10.1158/1078-0432.ccr-17-3763.Peer-Reviewed Original ResearchConceptsImmune-related adverse eventsMarrow complete responseMyelodysplastic syndromeGrade 2T cellsHigher immune-related adverse eventsHigh-risk myelodysplastic syndromeT-cell receptor sequencingRisk myelodysplastic syndromesInvestigator-initiated trialClin Cancer ResDrug discontinuationHMA failureStable diseaseSystemic steroidsAdverse eventsMedian survivalComplete responseDismal survivalAdditional patientsClinical benefitTreatment optionsExcessive toxicityPatientsDose levels
2017
A phase I trial of ipilimumab (ipi) in patients (pts) with myelodysplastic syndromes (MDS) after hypomethylating agent (HMAs) failure.
Zeidan A, Knaus H, Robinson T, Zeidner J, Blackford A, Rizzieri D, Frattini M, Levy M, Schroeder M, Ferguson A, Sheldon K, Dezern A, Gojo I, Gore S, Streicher H, Luznik L, Duffield A, Smith B. A phase I trial of ipilimumab (ipi) in patients (pts) with myelodysplastic syndromes (MDS) after hypomethylating agent (HMAs) failure. Journal Of Clinical Oncology 2017, 35: 7010-7010. DOI: 10.1200/jco.2017.35.15_suppl.7010.Peer-Reviewed Original ResearchImmune-related adverse eventsOverall survivalMyelodysplastic syndromeHMA failureDose levelsMarrow complete responsePhase 1b studyCTLA-4 blockadeMedian overall survivalImmune checkpoint blockadeKaplan-Meier methodPhase I trialPoor overall survivalExpression of ICOST cell activationDrug discontinuationHR-MDSStable diseaseSystemic steroidsAdverse eventsCheckpoint blockadeClinical responseMaintenance doseObjective responseAllogeneic transplantation
2016
Phase 1 Study of Pomalidomide Given at the Time of Early Lymphocyte Recovery after Induction Timed Sequential Chemotherapy in Newly Diagnosed Acute Myeloid Leukemia (AML) and High-Risk Myelodysplastic Syndrome (HR-MDS)
Zeidner J, Montiel-Esparza R, Knaus H, Berglund S, Zeidan A, McCurdy S, Prince G, Gondek L, Ghiaur G, Showel M, DeZern A, Pratz K, Smith B, Levis M, Foster M, Jamieson K, Van Deventer H, Streicher H, Karp J, Luznik L, Gojo I. Phase 1 Study of Pomalidomide Given at the Time of Early Lymphocyte Recovery after Induction Timed Sequential Chemotherapy in Newly Diagnosed Acute Myeloid Leukemia (AML) and High-Risk Myelodysplastic Syndrome (HR-MDS). Blood 2016, 128: 2820. DOI: 10.1182/blood.v128.22.2820.2820.Peer-Reviewed Original ResearchEarly lymphocyte recoveryAcute myeloid leukemiaWhite blood cell countComplete remissionAdverse eventsT cellsLymphocyte recoveryDay 1Adverse-risk acute myeloid leukaemiaDose levelsALT increasePhase 1 dose-escalation studyAST/ALT increaseContinuous infusion days 1High-risk myelodysplastic syndromeCore-binding factor acute myeloid leukemiaTotal white blood cell countFlow cytometryFactor acute myeloid leukemiaFull recoveryGrade 3 hypoxiaIncomplete platelet recoveryInfusion days 1Common adverse eventsConventional chemotherapy regimens
2015
Stabilization of Myelodysplastic Syndromes (MDS) Following Hypomethylating Agent (HMAs) Failure Using the Immune Checkpoint Inhibitor Ipilimumab: A Phase I Trial
Zeidan A, Zeidner J, Duffield A, Knaus H, Ferguson A, Sheldon K, DeZern A, Gojo I, Gore S, Streicher H, Luznik L, Smith B. Stabilization of Myelodysplastic Syndromes (MDS) Following Hypomethylating Agent (HMAs) Failure Using the Immune Checkpoint Inhibitor Ipilimumab: A Phase I Trial. Blood 2015, 126: 1666. DOI: 10.1182/blood.v126.23.1666.1666.Peer-Reviewed Original ResearchOverall survivalStable diseaseEnd of inductionMyelodysplastic syndromeFirst doseIpilimumab useMaintenance doseAnti-cytotoxic T-lymphocyte-associated protein 4 antibodyDose levelsInternational Working Group 2006 criteriaMedian white blood cell countImmune checkpoint inhibition therapyImmune checkpoint inhibitor ipilimumabMedian absolute neutrophil countAllogeneic stem cell transplantationWhite blood cell countT cell receptor repertoireBM blast percentageCheckpoint inhibitor ipilimumabDose-escalation partGrade 3 irAEsOngoing stable diseasePhase 1b studyProlonged disease stabilizationTolerability of ipilimumab