2020
Phase 1 study of belinostat (PXD-101) and bortezomib (Velcade, PS-341) in patients with relapsed or refractory acute leukemia and myelodysplastic syndrome
Holkova B, Shafer D, Yazbeck V, Dave S, Bose P, Tombes MB, Shrader E, Wan W, Bandyopadhyay D, Weir C, Collins EB, Garnett A, Kmieciak M, Roberts JD, Garcia-Manero G, Grant S. Phase 1 study of belinostat (PXD-101) and bortezomib (Velcade, PS-341) in patients with relapsed or refractory acute leukemia and myelodysplastic syndrome. Leukemia & Lymphoma 2020, 62: 1187-1194. PMID: 33356689, PMCID: PMC8106643, DOI: 10.1080/10428194.2020.1861270.Peer-Reviewed Original ResearchConceptsStable diseaseAcute leukemiaDay 1Phase 1 dose-escalation studyRefractory acute leukemiaDose-escalation studyPhase 1 studyWhole-exome sequencingComplete pathologicKaryotypic responseAdult patientsQTc prolongationFirst patientMyelodysplastic syndromeTreatment strategiesBlast crisisPatientsExceptional responseKaryotypic aberrationsBelinostatGood responseBortezomibAMLLeukemiaFurther investigation
2013
A Phase I Trial of Vorinostat and Alvocidib in Patients with Relapsed, Refractory, or Poor Prognosis Acute Leukemia, or Refractory Anemia with Excess Blasts-2
Holkova B, Supko JG, Ames MM, Reid JM, Shapiro GI, Perkins EB, Ramakrishnan V, Tombes MB, Honeycutt C, McGovern RM, Kmieciak M, Shrader E, Wellons MD, Sankala H, Doyle A, Wright J, Roberts JD, Grant S. A Phase I Trial of Vorinostat and Alvocidib in Patients with Relapsed, Refractory, or Poor Prognosis Acute Leukemia, or Refractory Anemia with Excess Blasts-2. Clinical Cancer Research 2013, 19: 1873-1883. PMID: 23515411, PMCID: PMC3618599, DOI: 10.1158/1078-0432.ccr-12-2926.Peer-Reviewed Original ResearchMeSH KeywordsAcute DiseaseAdultAgedAnemia, Refractory, with Excess of BlastsAntineoplastic Combined Chemotherapy ProtocolsCell Line, TumorCyclin-Dependent Kinase Inhibitor p21FemaleFlavonoidsHumansHydroxamic AcidsLeukemiaMaleMaximum Tolerated DoseMiddle AgedMyeloid Cell Leukemia Sequence 1 ProteinPiperidinesPrognosisProto-Oncogene Proteins c-bcl-2RecurrenceRNA Polymerase IITreatment OutcomeVorinostatYoung AdultConceptsMaximum-tolerated dosePoor-prognosis acute leukemiaExcess blasts-2Objective responseQT prolongationAcute leukemiaBlasts-2Phase I trialBone marrow responseCardiac arrhythmia atrial fibrillationArrhythmia atrial fibrillationEvaluable patientsStable diseaseVorinostat pharmacokineticsDisease stabilizationMaintenance infusionI trialMarrow responsePharmacodynamic effectsRefractory anemiaIntravenous infusionLoading infusionPatientsVorinostatSecondary objective
2012
Phase I Trial of Belinostat and Bortezomib in Patients with Relapsed or Refractory Acute Leukemia, Myelodysplastic Syndrome, or Chronic Myelogenous Leukemia in Blast Crisis - One Year Update
Holkova B, Bose P, Tombes M, Shrader E, Wan W, Weir-Wiggins C, Stoddert E, Sankala H, Kmieciak M, Roberts J, Garcia-Manero G, Grant S. Phase I Trial of Belinostat and Bortezomib in Patients with Relapsed or Refractory Acute Leukemia, Myelodysplastic Syndrome, or Chronic Myelogenous Leukemia in Blast Crisis - One Year Update. Blood 2012, 120: 3588. DOI: 10.1182/blood.v120.21.3588.3588.Peer-Reviewed Original ResearchHematopoietic stem cell transplantationStem cell transplantationAcute myeloid leukemiaRefractory acute leukemiaDose level 5Myelodysplastic syndromeStable diseaseCycles of treatmentPartial responseComplete responseAcute leukemiaChronic myelogenous leukemiaCML-BCAdverse eventsI trialMyelogenous leukemiaDay 1Allogeneic hematopoietic stem cell transplantationIncomplete blood count recoveryTreatment-related adverse eventsPrimary acute myeloid leukemiaAcute leukemia refractoryBlood count recoveryDose level 4Second partial response
2011
Phase I Trial of Belinostat and Bortezomib in Patients with Relapsed or Refractory Acute Leukemia, Myelodysplastic Syndrome, or Chronic Myelogenous Leukemia in Blast Crisis
Holkova B, Tombes M, Shrader E, Cooke S, Wan W, Sankala H, Kmieciak M, Roberts J, Garcia-Manero G, Grant S. Phase I Trial of Belinostat and Bortezomib in Patients with Relapsed or Refractory Acute Leukemia, Myelodysplastic Syndrome, or Chronic Myelogenous Leukemia in Blast Crisis. Blood 2011, 118: 2598. DOI: 10.1182/blood.v118.21.2598.2598.Peer-Reviewed Original ResearchRefractory acute leukemiaMyelodysplastic syndromeAcute leukemiaChronic myelogenous leukemiaMyelogenous leukemiaI trialCML-BCBlast crisisDay 1ECOG performance score 0Hematopoietic stem cell transplantationPerformance score 0Phase II dosesRecent preclinical findingsPeripheral sensory neuropathySerious adverse eventsMinute intravenous infusionPhase I trialPhase II evaluationPrimary acute myelogenous leukemiaSchedule of administrationStem cell transplantationBiphenotypic acute leukemiaCombination of bortezomibAcute myelogenous leukemia
2008
Phase I Trial of Vorinostat (SAHA) in Combination with Alvocidib (Flavopiridol) in Patients with Relapsed, Refractory or (Selected) Poor Prognosis Acute Leukemia or Refractory Anemia with Excess Blasts-2 (RAEB-2)
Grant S, Kolla S, Sirulnik L, Shapiro G, Supko J, Cooper B, Perkins E, Ramakrishnan V, Espinoza-Delgado I, Tombes M, Roberts J. Phase I Trial of Vorinostat (SAHA) in Combination with Alvocidib (Flavopiridol) in Patients with Relapsed, Refractory or (Selected) Poor Prognosis Acute Leukemia or Refractory Anemia with Excess Blasts-2 (RAEB-2). Blood 2008, 112: 2986. DOI: 10.1182/blood.v112.11.2986.2986.Peer-Reviewed Original ResearchAcute leukemiaDose levelsStandard therapyI trialDay 1Grade 4 non-hematologic toxicityPoor-prognosis acute leukemiaDe novo acute leukemiaExcess blasts-2High-risk AMLNon-hematologic toxicitiesRemission induction failurePoor risk factorsImatinib-Refractory Chronic Myeloid LeukemiaPhase I trialPhase II evaluationAML/MDSCorrelative laboratory studiesNovo acute leukemiaChronic myeloid leukemiaHDAC inhibitor vorinostatCDK inhibitor flavopiridolAbsence of leukemiaPost-treatment effectsBolus schedule
2002
Phase I trial and correlative laboratory studies of bryostatin 1 (NSC 339555) and high-dose 1-B-D-arabinofuranosylcytosine in patients with refractory acute leukemia.
Cragg LH, Andreeff M, Feldman E, Roberts J, Murgo A, Winning M, Tombes MB, Roboz G, Kramer L, Grant S. Phase I trial and correlative laboratory studies of bryostatin 1 (NSC 339555) and high-dose 1-B-D-arabinofuranosylcytosine in patients with refractory acute leukemia. Clinical Cancer Research 2002, 8: 2123-33. PMID: 12114412.Peer-Reviewed Original ResearchConceptsDose-limiting toxicityPhase I trialComplete remissionCorrelative laboratory studiesI trialAcute leukemiaSplit courseContinuous infusionVivo administrationBryostatin 1Ara-C dose levelsAutologous bone marrow transplantationMajor dose-limiting toxicityEx vivoRefractory acute leukemiaUnfavorable prognostic characteristicsHigh-risk featuresLeukemia-free survivalBone marrow transplantationCourse of therapyPKC activityTransfusion requirementsRefractory leukemiaRefractory/Latter patients