2024
Oral decitabine–cedazuridine versus intravenous decitabine for myelodysplastic syndromes and chronic myelomonocytic leukaemia (ASCERTAIN): a registrational, randomised, crossover, pharmacokinetics, phase 3 study
Garcia-Manero G, McCloskey J, Griffiths E, Yee K, Zeidan A, Al-Kali A, Deeg H, Patel P, Sabloff M, Keating M, Zhu N, Gabrail N, Fazal S, Maly J, Odenike O, Kantarjian H, DeZern A, O'Connell C, Roboz G, Busque L, Buckstein R, Amin H, Randhawa J, Leber B, Shastri A, Dao K, Oganesian A, Hao Y, Keer H, Azab M, Savona M. Oral decitabine–cedazuridine versus intravenous decitabine for myelodysplastic syndromes and chronic myelomonocytic leukaemia (ASCERTAIN): a registrational, randomised, crossover, pharmacokinetics, phase 3 study. The Lancet Haematology 2024, 11: e15-e26. PMID: 38135371, DOI: 10.1016/s2352-3026(23)00338-1.Peer-Reviewed Original ResearchConceptsChronic myelomonocytic leukemiaIntravenous decitabineMyelodysplastic syndromeMyelomonocytic leukemiaOral therapyPrimary endpointAdverse eventsEastern Cooperative Oncology Group performance status 0Treatment cyclesCycle 1Full treatment dosePerformance status 0Treatment-related deathsFrequent adverse eventsSerious adverse eventsPhase 3 studyPhase 3 trialPotential treatment benefitsCommunity-based clinicsAcute myeloid leukemiaNext treatment cycleTreatment of individualsOral decitabineStatus 0Treatment discontinuation
2023
Sabatolimab in Combination with Hypomethylating Agents (HMAs) Was Safe in Patients (Pts) with Intermediate-, High-, or Very-High-Risk Myelodysplastic Syndrome (MDS)
Garcia-Manero G, Lyons R, Nandal S, Ashraf M, Thellaboina R, Ruckel-Kumar J, Menssen H, Zeidan A. Sabatolimab in Combination with Hypomethylating Agents (HMAs) Was Safe in Patients (Pts) with Intermediate-, High-, or Very-High-Risk Myelodysplastic Syndrome (MDS). Blood 2023, 142: 4606. DOI: 10.1182/blood-2023-186490.Peer-Reviewed Original ResearchHigh-risk myelodysplastic syndromeAdverse eventsHematologic improvementPartial remissionMyelodysplastic syndromeHypomethylating agentMarrow CRInterim analysisStable diseaseData cutoffLast doseInternational Prognostic Scoring System criteriaResponse rateCount decreaseCycle 1 day 1Second-line treatment optionExtension phaseHematologic adverse eventsNeutrophil count decreaseOral hypomethylating agentPhase Ib studySerious adverse eventsFatal adverse eventsMonths of treatmentSingle-arm study
2021
MDS-364: STIMULUS MDS-US Trial in Progress: Evaluating Sabatolimab in Combination with Hypomethylating Agents (HMAs) in Patients with Intermediate-, High-, or Very High–Risk Myelodysplastic Syndromes (MDS)
Zeidan A, DeZern A, Borate U, Kobata K, Sadek I, Sabo J, Purkayastha D, Ramos P, Sun H, Lyons R, Garcia-Manero G. MDS-364: STIMULUS MDS-US Trial in Progress: Evaluating Sabatolimab in Combination with Hypomethylating Agents (HMAs) in Patients with Intermediate-, High-, or Very High–Risk Myelodysplastic Syndromes (MDS). Clinical Lymphoma Myeloma & Leukemia 2021, 21: s348-s349. DOI: 10.1016/s2152-2650(21)01808-5.Peer-Reviewed Original ResearchHigh-risk myelodysplastic syndromeMyelodysplastic syndromeHypomethylating agentAdverse eventsInvestigator's choiceCR/PRHematopoietic stem cell transplantDuration of CROral hypomethylating agentLeukemia-free survivalPhase Ib studyPhase II studySerious adverse eventsComplete remission ratePercentage of patientsProgression-free survivalMonths of treatmentStem cell transplantFavorable safety profileExperience poor outcomesNormal hematopoietic stem cellsMultiple phase IMyeloid leukemic cellsEligible patientsOral decitabine
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