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-offEfficacy and Safety of Pembrolizumab Added to Azacitidine Plus Venetoclax for Patients with Acute Myeloid Leukemia: Results from an Investigator-Initiated, Multi-Center, CTEP-Sponsored Randomized, Phase II Trial (BLAST AML-2)
Stempel J, Uy G, Dinner S, Gojo I, Reed D, Roy R, Byrd K, Yerrabothala S, Lai C, Doucette K, Caldwell A, Blaha O, Podoltsev N, Mendez L, Bewersdorf J, Kewan T, Wistuba I, Alatrash G, Haymaker C, Streicher H, Sharon E, Little R, Gore S, Radich J, Wood B, Zeidan A, Shallis R. Efficacy and Safety of Pembrolizumab Added to Azacitidine Plus Venetoclax for Patients with Acute Myeloid Leukemia: Results from an Investigator-Initiated, Multi-Center, CTEP-Sponsored Randomized, Phase II Trial (BLAST AML-2). Blood 2024, 144: 736. DOI: 10.1182/blood-2024-210370.Peer-Reviewed Original ResearchPhase II trialTreatment-related AEsII trialFrequent treatment-related AEsSafety run-in periodAllogeneic stem cell transplantationNo dose limiting toxicitiesRandomized phase II trialAML-2Multi-centerControl armSafety of pembrolizumabDose-limiting toxicityPD-1 inhibitionAnti-PD1 antibodyIncomplete count recoveryFLT3 wild-typeIntermediate cytogenetic riskStem cell transplantationAcute myeloid leukemiaActivated T cellsRun-in periodIntention-to-treat analysisCancer Immune MonitoringLong-term survivalZiftomenib 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 cytarabineResults from a Phase 1 Open-Label Dose Escalation and Expansion Trial of Oral Azacitidine + Cedazuridine (ASTX030) in Patients with Myelodysplastic Syndromes (MDS) and MDS/Myeloproliferative Neoplasms (MPN)
Garcia-Manero G, McCloskey J, Scott B, Griffiths E, Kiner-Strachan B, Brunner A, Zeidan A, Traer E, Madanat Y, Meyer J, Erba H, Baratam P, Borate U, Sano Y, Oganesian A, Zhu L, Keer H, Savona M. Results from a Phase 1 Open-Label Dose Escalation and Expansion Trial of Oral Azacitidine + Cedazuridine (ASTX030) in Patients with Myelodysplastic Syndromes (MDS) and MDS/Myeloproliferative Neoplasms (MPN). Blood 2024, 144: 662. DOI: 10.1182/blood-2024-203569.Peer-Reviewed Original ResearchDose-limiting toxicityPhase 1 trialDose-expansion partMDS/MPN overlap syndromesMyelodysplastic syndromeAdverse eventsDose combinationMDS/myeloproliferative neoplasmImmediate-releaseOverlap syndromeAUC exposureOpen-label phase 1 trialDelayed-releaseCytidine deaminaseProlonged grade 4 neutropeniaIncreased absolute bioavailabilityMarrow complete responsePhase 2 doseGrade 4 neutropeniaDose-escalation partErythropoiesis-stimulating agentsAcute myeloid leukemiaTreatment of patientsClinical efficacy assessmentDNA methyltransferase inhibitor
2023
A multicenter phase Ib trial of the histone deacetylase inhibitor entinostat in combination with pembrolizumab in patients with myelodysplastic syndromes/neoplasms or acute myeloid leukemia refractory to hypomethylating agents
Bewersdorf J, Shallis R, Sharon E, Park S, Ramaswamy R, Roe C, Irish J, Caldwell A, Wei W, Yacoub A, Madanat Y, Zeidner J, Altman J, Odenike O, Yerrabothala S, Kovacsovics T, Podoltsev N, Halene S, Little R, Piekarz R, Gore S, Kim T, Zeidan A. A multicenter phase Ib trial of the histone deacetylase inhibitor entinostat in combination with pembrolizumab in patients with myelodysplastic syndromes/neoplasms or acute myeloid leukemia refractory to hypomethylating agents. Annals Of Hematology 2023, 103: 105-116. PMID: 38036712, DOI: 10.1007/s00277-023-05552-4.Peer-Reviewed Original ResearchConceptsDose-limiting toxicityAcute myeloid leukemiaMarrow complete remissionPhase Ib trialAdverse eventsIb trialDose escalationNCI Cancer Therapy Evaluation ProgramAcute myeloid leukemia refractoryHematologic adverse eventsProtocol-defined responseDose level 1Anti-PD1 therapyAnti-PD1 antibodyDose-escalation designLimited clinical efficacySystems immunology approachHistone deacetylase inhibitor entinostatLeukemia refractoryMCR patientsComplete remissionRespiratory failureSuppressor cellsEscalation designClinical efficacySafety, Pharmacodynamic, and Anti-Tumor Activity of SL-172154 As Monotherapy and in Combination with Azacitidine (AZA) in Relapsed/Refractory (R/R) Acute Myeloid Leukemia (AML) and Higher-Risk Myelodysplastic Syndromes/Neoplasms (HR-MDS) Patients (pts)
Daver N, Stein A, Bixby D, Chai-Ho W, Zeidner J, Maher K, Stevens D, Stahl M, Yee K, Curran E, Ito S, Sochacki A, Sallman D, Hernandez R, Metenou S, Ma B, Kato K, Zeidan A. Safety, Pharmacodynamic, and Anti-Tumor Activity of SL-172154 As Monotherapy and in Combination with Azacitidine (AZA) in Relapsed/Refractory (R/R) Acute Myeloid Leukemia (AML) and Higher-Risk Myelodysplastic Syndromes/Neoplasms (HR-MDS) Patients (pts). Blood 2023, 142: 4278. DOI: 10.1182/blood-2023-173991.Peer-Reviewed Original ResearchR AMLAcute myeloid leukemiaTreatment-emergent AEsInfusion-related reactionsDose-limiting toxicityDose-escalation cohortsHR-MDSDose-dependent increaseComplete remissionObjective responseAnti-tumor activityBone marrowHypomethylating agentAllo-HCTAML ptsEvaluable ptsEscalation cohortsDose escalationRelapsed/Refractory Acute Myeloid LeukemiaMedian age 70 yearsMorphologic leukemia-free statePhase 1 dose escalationSIRPα-Fc fusion proteinRefractory acute myeloid leukemiaMarrow complete remissionPhase 1/2 Study of the Pan-PIM Kinase Inhibitor INCB053914 Alone or in Combination With Standard-of-Care Agents in Patients With Advanced Hematologic Malignancies
Patel M, Donnellan W, Byrne M, Asch A, Zeidan A, Baer M, Fathi A, Kuykendall A, Zheng F, Walker C, Cheng L, Marando C, Savona M. Phase 1/2 Study of the Pan-PIM Kinase Inhibitor INCB053914 Alone or in Combination With Standard-of-Care Agents in Patients With Advanced Hematologic Malignancies. Clinical Lymphoma Myeloma & Leukemia 2023, 23: 674-686. PMID: 37290996, DOI: 10.1016/j.clml.2023.05.002.Peer-Reviewed Original ResearchConceptsTreatment-emergent adverse eventsDose-limiting toxicityAdvanced hematologic malignanciesAcute myeloid leukemiaMyelodysplastic syndromeHematologic malignanciesCare agentsHigh-risk myelodysplastic syndromeMDS/myeloproliferative neoplasmPhase 1/2 studyEffective combination strategiesAdverse eventsComplete responseLymphoproliferative neoplasmsWeek 12Multiple myelomaSpleen volumeAcute leukemiaMyeloid leukemiaPreclinical modelsPatientsMyeloproliferative neoplasmsMoloney murine leukemia virus (PIM) kinasesMyelofibrosisKinase inhibitors
2022
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)
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
2020
A Phase Ib Study of Onvansertib, a Novel Oral PLK1 Inhibitor, in Combination Therapy for Patients with Relapsed or Refractory Acute Myeloid Leukemia
Zeidan AM, Ridinger M, Lin TL, Becker PS, Schiller GJ, Patel PA, Spira AI, Tsai ML, Samuëlsz E, Silberman SL, Erlander M, Wang ES. A Phase Ib Study of Onvansertib, a Novel Oral PLK1 Inhibitor, in Combination Therapy for Patients with Relapsed or Refractory Acute Myeloid Leukemia. Clinical Cancer Research 2020, 26: 6132-6140. PMID: 32998961, DOI: 10.1158/1078-0432.ccr-20-2586.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsCytarabineDecitabineDrug Resistance, NeoplasmFemaleFollow-Up StudiesHumansLeukemia, Myeloid, AcuteMaleMaximum Tolerated DoseMiddle AgedNeoplasm Recurrence, LocalPiperazinesPrognosisPyrazolesQuinazolinesSalvage TherapyConceptsAcute myeloid leukemiaPhase Ib studyMyeloid leukemiaIb studyRefractory (R/R) AMLFirst-cycle dose-limiting toxicitiesRefractory acute myeloid leukemiaOngoing phase II trialAntileukemic activityMost grade 3Low-dose cytarabinePhase II trialBone marrow blastsDose-limiting toxicityPLK1 inhibitorsPolo-like kinase 1Evaluable patientsExploratory endpointsComplete remissionII trialPrimary endpointAdverse eventsClinical responseMarrow blastsCount recovery
2011
Escalation Trial of Clofarabine Followed by Escalating Dose of Fractionated Cyclophosphamide in Adults with Relapsed or Refractory Acute Leukemias,
Zeidan A, Carraway H, Yun H, Greer J, Karp J. Escalation Trial of Clofarabine Followed by Escalating Dose of Fractionated Cyclophosphamide in Adults with Relapsed or Refractory Acute Leukemias,. Blood 2011, 118: 3615. DOI: 10.1182/blood.v118.21.3615.3615.Peer-Reviewed Original ResearchRefractory acute leukemiaAbsolute lymphocyte countAbsolute neutrophilic countDose level 1Dose-limiting toxicityOverall response rateAdverse cytogeneticsWhite blood cellsM2/dayClinical responseAcute leukemiaDay 1One-year disease-free survivalPhase I dose-escalation trialMedian absolute lymphocyte countElevated liver function testsAllogeneic stem cell transplantI dose-escalation trialTotal white blood cellsSecond-generation purine nucleoside analogDose level 3Dose level 4Dose of CYGrade 3 pneumoniaHand-foot syndrome