2021
Non-crisis related pain occurs in adult patients with sickle cell disease despite chronic red blood cell exchange transfusion therapy
Curtis SA, Raisa BM, Roberts JD, Hendrickson JE, Starrels J, Lesley D, Michelle D, Daniel Z, Brandow AM. Non-crisis related pain occurs in adult patients with sickle cell disease despite chronic red blood cell exchange transfusion therapy. Transfusion And Apheresis Science 2021, 61: 103304. PMID: 34782244, PMCID: PMC9838733, DOI: 10.1016/j.transci.2021.103304.Peer-Reviewed Original ResearchConceptsChronic exchange transfusionsHealth care utilizationCare utilizationExchange transfusionPain impactDisease characteristicsChronic red blood cell transfusionsRed blood cell transfusionLower health care utilizationSickle Cell Disease PainExchange transfusion therapyAcute care utilizationBlood cell transfusionSimilar disease characteristicsPatient-reported outcomesLength of staySickle cell diseaseQuality of lifeCause admissionsCell transfusionNeuropathic painOpioid prescriptionsWorst painAcute painAdult patients
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 investigationMedical marijuana certification for patients with sickle cell disease: a report of a single center experience
Curtis SA, Lew D, Spodick J, Hendrickson JE, Minniti CP, Roberts JD. Medical marijuana certification for patients with sickle cell disease: a report of a single center experience. Blood Advances 2020, 4: 3814-3821. PMID: 32790846, PMCID: PMC7448584, DOI: 10.1182/bloodadvances.2020002325.Peer-Reviewed Original ResearchConceptsOpioid useMedical marijuanaSickle cell disease (SCD) reportBaseline opioid useSingle-center experienceHealth care utilizationSickle cell diseaseOpioid utilizationClinical characteristicsMost patientsCenter experienceCare utilizationSCD patientsInpatient hospitalizationRandom patientsAdmission ratesCell diseasePatientsRetrospective dataDisease reportsStudy periodHealth careCannabis productsCannabisEdible cannabis productsBuilding access to care in adult sickle cell disease: defining models of care, essential components, and economic aspects
Kanter J, Smith WR, Desai PC, Treadwell M, Andemariam B, Little J, Nugent D, Claster S, Manwani DG, Baker J, Strouse JJ, Osunkwo I, Stewart RW, King A, Shook LM, Roberts JD, Lanzkron S. Building access to care in adult sickle cell disease: defining models of care, essential components, and economic aspects. Blood Advances 2020, 4: 3804-3813. PMID: 32785684, PMCID: PMC7448595, DOI: 10.1182/bloodadvances.2020001743.Peer-Reviewed Original ResearchConceptsSickle cell diseaseSCD centerCell diseaseAdult sickle cell diseaseAcute care utilizationManagement of adultsModel of careSickle cell careHealth care professionalsHealth system levelSCD guidelinesMultisystem illnessSCD careCare utilizationEarly mortalityCenter designationClinical effectivenessClinical centersCare professionalsHematology providersMore cliniciansCare deliveryMost childrenBlood disordersCareUtilization, financial outcomes and stakeholder perspectives of a re-organized adult sickle cell program
Rousseau R, Weisberg DF, Gorero J, Parwani V, Bozzo J, Kenyon K, Smith C, Cole J, Curtis S, Forray A, Roberts JD. Utilization, financial outcomes and stakeholder perspectives of a re-organized adult sickle cell program. PLOS ONE 2020, 15: e0236360. PMID: 32706825, PMCID: PMC7380627, DOI: 10.1371/journal.pone.0236360.Peer-Reviewed Original ResearchConceptsSickle cell diseaseCell diseaseYale-New Haven HospitalAcute care servicesCare of adultsPoor socio-economic statusPersonalized care planSickle Cell ProgramNew Haven HospitalSingle nursing unitParenteral opioidsPain controlClinic visitsMost patientsPain managementChronic painOutpatient visitsPrimary complaintEmergency departmentPrimary careInpatient daysCare plansCare servicesSocio-economic statusNursing units
2019
Red blood cell alloimmunization is associated with lower expression of FcγR1 on monocyte subsets in patients with sickle cell disease
Balbuena‐Merle R, Curtis SA, Devine L, Gibb DR, Karafin MS, Luckey CJ, Tormey CA, Siddon AJ, Roberts JD, Hendrickson JE. Red blood cell alloimmunization is associated with lower expression of FcγR1 on monocyte subsets in patients with sickle cell disease. Transfusion 2019, 59: 3219-3227. PMID: 31355970, PMCID: PMC7075520, DOI: 10.1111/trf.15463.Peer-Reviewed Original ResearchConceptsSickle cell diseaseMonocyte subsetsTotal monocytesCell diseaseComplications of SCDRed blood cell alloimmunizationRed blood cell alloantibodiesElectronic medical recordsTransfusion exposureSerum cytokinesIntermediate monocytesRBC alloantibodiesInflammatory milieuCD64 expressionClassical monocytesPeripheral bloodInflammatory functionsMedical recordsAntibody formationClinical significancePatientsMonocytesFlow cytometryLow expressionRespondersPrescription Opioid Misuse Index in sickle cell patients: A brief questionnaire to assess at-risk for opioid abuse.
Smith WR, McClish DK, Roberts JD, Kandalaft O, Dahman B, Knisely J, Levenson J, Roseff S, Aisiku IP. Prescription Opioid Misuse Index in sickle cell patients: A brief questionnaire to assess at-risk for opioid abuse. Journal Of Opioid Management 2019, 15: 323-331. PMID: 31637684, DOI: 10.5055/jom.2019.0517.Peer-Reviewed Original ResearchConceptsOpioid misuseOpioid abuseAdult sickle cell disease patientsPrescription Opioid Misuse IndexSickle cell disease patientsAdult SCD patientsChronic opioid therapyGroup of patientsSickle cell clinicSickle cell patientsDiagnostic Interview ScheduleDSM-IV criteriaUrban teaching facilityOpioid therapySCD clinicOpioid usageAdult patientsRisk patientsSecondary outcomesHemoglobin SSPrimary outcomeSCD patientsMean ageDisease patientsProspective survey
2018
A Phase II Trial of Bortezomib and Vorinostat in Mantle Cell Lymphoma and Diffuse Large B-cell Lymphoma
Yazbeck V, Shafer D, Perkins EB, Coppola D, Sokol L, Richards KL, Shea T, Ruan J, Parekh S, Strair R, Flowers C, Morgan D, Kmieciak M, Bose P, Kimball A, Badros AZ, Baz R, Lin HY, Zhao X, Reich RR, Tombes MB, Shrader E, Sankala H, Roberts JD, Sullivan D, Grant S, Holkova B. A Phase II Trial of Bortezomib and Vorinostat in Mantle Cell Lymphoma and Diffuse Large B-cell Lymphoma. Clinical Lymphoma Myeloma & Leukemia 2018, 18: 569-575.e1. PMID: 30122201, DOI: 10.1016/j.clml.2018.05.023.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsBortezomibDrug Resistance, NeoplasmFemaleFollow-Up StudiesHumansLymphoma, Large B-Cell, DiffuseLymphoma, Mantle-CellMaleMiddle AgedNeoplasm Recurrence, LocalPrognosisProspective StudiesSalvage TherapySurvival RateVorinostatConceptsLarge B-cell lymphomaPhase II trialStable diseaseProgressive diseaseB-cell lymphomaPartial responseII trialCohort BCohort ADay 1Median progression-free survivalNonrandomized phase II trialDiffuse large B-cell lymphomaProgression-free survivalHistone deacetylase inhibitor vorinostatOverall response rateCombination of bortezomibMantle cell lymphomaNF-κB activationProteasome inhibitor bortezomibCell lymphoma cellsPresent multicenterRefractory MCLClinical responseCohort C
2017
Predictive Ability of Intermittent Daily Sickle Cell Pain Assessment: The PiSCES Project
Smith WR, McClish DK, Levenson J, Aisiku I, Dahman B, Bovbjerg VE, Roseff S, Roberts J. Predictive Ability of Intermittent Daily Sickle Cell Pain Assessment: The PiSCES Project. Pain Medicine 2017, 19: 1972-1981. PMID: 29036363, PMCID: PMC6176749, DOI: 10.1093/pm/pnx214.Peer-Reviewed Original ResearchConceptsSickle cell diseasePain daysPain assessmentPain measuresOne weekGold standardSickle Cell Epidemiology StudyMonths strategyDaily pain assessmentProspective cohort studyOne dayPiSCES projectCohort studySCD patientsMeasurement of R2Month assessmentCell diseasePainEpidemiology studiesDiary assessmentsDaily assessmentIntermittent assessmentCrisis daysWeeksMonthsComorbidity, Pain, Utilization, and Psychosocial Outcomes in Older versus Younger Sickle Cell Adults: The PiSCES Project
McClish DK, Smith WR, Levenson JL, Aisiku IP, Roberts JD, Roseff SD, Bovbjerg VE. Comorbidity, Pain, Utilization, and Psychosocial Outcomes in Older versus Younger Sickle Cell Adults: The PiSCES Project. BioMed Research International 2017, 2017: 4070547. PMID: 28459058, PMCID: PMC5387810, DOI: 10.1155/2017/4070547.Peer-Reviewed Original ResearchConceptsSickle Cell Epidemiology StudyHealth care utilizationPain daysPiSCES projectPain frequencyAmbulatory visitsPain intensityCare utilizationPainComorbiditiesEpidemiology studiesPsychosocial measuresAge groupsAdult groupPsychosocial outcomesPsychosocial variablesOlder adultsSomatic complaintsHealth careBehavioral coping strategiesTransition groupFurther studiesPatientsAdultsSCDEffect of Longer-Interval vs Standard Dosing of Zoledronic Acid on Skeletal Events in Patients With Bone Metastases: A Randomized Clinical Trial
Himelstein AL, Foster JC, Khatcheressian JL, Roberts JD, Seisler DK, Novotny PJ, Qin R, Go RS, Grubbs SS, O’Connor T, Velasco MR, Weckstein D, O’Mara A, Loprinzi CL, Shapiro CL. Effect of Longer-Interval vs Standard Dosing of Zoledronic Acid on Skeletal Events in Patients With Bone Metastases: A Randomized Clinical Trial. JAMA 2017, 317: 48-58. PMID: 28030702, PMCID: PMC5321662, DOI: 10.1001/jama.2016.19425.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overBone and BonesBone Density Conservation AgentsBone NeoplasmsBreast NeoplasmsDiphosphonatesDrug Administration ScheduleFemaleHumansImidazolesMaleMiddle AgedMultiple MyelomaPain MeasurementProstatic NeoplasmsSample SizeSpinal Cord CompressionSpinal FracturesZoledronic AcidConceptsSkeletal morbidity rateProportion of patientsDosing groupZoledronic acidBone metastasesMultiple myelomaProstate cancerBreast cancerSkeletal eventsKidney dysfunctionBone turnoverMorbidity rateClinical trialsEastern Cooperative Oncology Group performance statusOpen-label clinical trialEnd pointIncidence of osteonecrosisYear of randomizationPerformance status scorePrimary end pointSecondary end pointsBrief Pain InventoryMetastatic breast cancerMetastatic prostate cancerAcceptable treatment option
2016
Phase I study of pemetrexed with sorafenib in advanced solid tumors
Poklepovic A, Gordon S, Shafer DA, Roberts JD, Bose P, Geyer CE, McGuire WP, Tombes MB, Shrader E, Strickler K, Quigley M, Wan W, Kmieciak M, Massey HD, Booth L, Moran RG, Dent P. Phase I study of pemetrexed with sorafenib in advanced solid tumors. Oncotarget 2016, 7: 42625-42638. PMID: 27213589, PMCID: PMC5173162, DOI: 10.18632/oncotarget.9434.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorCohort StudiesFemaleHumansInflammationMaleMaximum Tolerated DoseMiddle AgedNeoplasmsNiacinamidePemetrexedPhenylurea CompoundsPTEN PhosphohydrolaseSorafenibTreatment OutcomeTriple Negative Breast NeoplasmsConceptsAdvanced solid tumorsDay 1Solid tumorsOral sorafenibDose scheduleBreast cancerTriple-negative breast cancerDose-escalation schemaPhase II dosePhase I trialSorafenib dosingSorafenib therapyStable diseaseCohort BComplete responseI trialPartial responseTolerable combinationRadiographic assessmentCumulative toxicityCombination treatmentPatientsSorafenibPhase IAntitumor activityA phase I study of indoximod in patients with advanced malignancies
Soliman HH, Minton SE, Han HS, Ismail-Khan R, Neuger A, Khambati F, Noyes D, Lush R, Chiappori AA, Roberts JD, Link C, Vahanian NN, Mautino M, Streicher H, Sullivan DM, Antonia SJ. A phase I study of indoximod in patients with advanced malignancies. Oncotarget 2016, 7: 22928-22938. PMID: 27008709, PMCID: PMC5008412, DOI: 10.18632/oncotarget.8216.Peer-Reviewed Original ResearchConceptsStable diseaseDose levelsC-reactive protein levelsReactive protein levelsAdvanced solid tumorsTumor-mediated immunosuppressionPhase I trialUntreated brain metastasesMetastatic solid malignanciesMultiple dose levelsAntigen autoantibodiesBrain metastasesCheckpoint inhibitorsImmune correlatesPrimary endpointSecondary endpointsAdvanced malignanciesCRP levelsI trialOral inhibitorAutoimmune diseasesMarrow functionSolid malignanciesInclusion criteriaExclusion criteriaA Phase II Trial of AZD6244 (Selumetinib, ARRY-142886), an Oral MEK1/2 Inhibitor, in Relapsed/Refractory Multiple Myeloma
Holkova B, Zingone A, Kmieciak M, Bose P, Badros AZ, Voorhees PM, Baz R, Korde N, Lin HY, Chen JQ, Herrmann M, Xi L, Raffeld M, Zhao X, Wan W, Tombes MB, Shrader E, Weir-Wiggins C, Sankala H, Hogan KT, Doyle A, Annunziata CM, Wellons M, Roberts JD, Sullivan D, Landgren O, Grant S. A Phase II Trial of AZD6244 (Selumetinib, ARRY-142886), an Oral MEK1/2 Inhibitor, in Relapsed/Refractory Multiple Myeloma. Clinical Cancer Research 2016, 22: 1067-1075. PMID: 26446942, PMCID: PMC4775365, DOI: 10.1158/1078-0432.ccr-15-1076.Peer-Reviewed Original ResearchConceptsRefractory multiple myelomaPartial responseMultiple myelomaRelapsed/Refractory Multiple MyelomaMedian progression-free survival timeResponse rateProgression-free survival timeTwo-stage Simon designCommon grade 3Good partial responsePhase II studyPhase II trialMEK1/2 inhibitorSignificant preclinical activityMultiple myeloma cellsPrior therapyStable diseaseII trialClinical responseII studyProgressive diseaseMedian ageMean durationPreclinical activityDisease progression
2015
Phase II trial of dasatinib for recurrent or metastatic c-KIT expressing adenoid cystic carcinoma and for nonadenoid cystic malignant salivary tumors
Wong SJ, Karrison T, Hayes DN, Kies MS, Cullen KJ, Tanvetyanon T, Argiris A, Takebe N, Lim D, Saba NF, Worden FP, Gilbert J, Lenz HJ, Razak AR, Roberts JD, Vokes EE, Cohen EE. Phase II trial of dasatinib for recurrent or metastatic c-KIT expressing adenoid cystic carcinoma and for nonadenoid cystic malignant salivary tumors. Annals Of Oncology 2015, 27: 318-323. PMID: 26598548, PMCID: PMC4722891, DOI: 10.1093/annonc/mdv537.Peer-Reviewed Original ResearchConceptsMalignant salivary gland tumorsAdverse eventsStable diseaseObjective responseACC patientsCystic carcinomaECOG performance status 0Grade 3 adverse eventsMedian age 56 yearsGrade 4 adverse eventsMedian progression-free survivalFrequent adverse eventsMedian overall survivalNon-ACC patientsPerformance status 0Noncardiac chest painPhase II studyPhase II trialProgression-free survivalAge 56 yearsMalignant salivary tumorsAdenoid cystic carcinomaSalivary gland tumorsCycle 2Prior chemotherapyDaily home opioid use in adults with sickle cell disease: The PiSCES project.
Smith WR, McClish DK, Dahman BA, Levenson JL, Aisiku IP, de A Citero V, Bovbjerg VE, Roberts JD, Penberthy LT, Roseff SD. Daily home opioid use in adults with sickle cell disease: The PiSCES project. Journal Of Opioid Management 2015, 11: 243-53. PMID: 25985809, DOI: 10.5055/jom.2015.0273.Peer-Reviewed Original ResearchMeSH KeywordsActivities of Daily LivingAdaptation, PsychologicalAdolescentAdultAnalgesics, OpioidAnemia, Sickle CellAntisickling AgentsCost of IllnessDrug Administration ScheduleDrug Therapy, CombinationFemaleHumansHydroxyureaLongitudinal StudiesMaleMiddle AgedPainPain MeasurementQuality of LifeSelf AdministrationTime FactorsTreatment OutcomeYoung AdultConceptsSickle cell diseaseHome opioid useOpioid usePain daysOpioid usersMean painCell diseasePsychosocial variablesDaily pain diaryMajority of patientsNon-opioid analgesicsSomatic symptom burdenPiSCES projectOpioid prescribingPain frequencyCohort studySymptom burdenPain diaryPain intensityPatient characteristicsPhysical QoLOpioidsPatientsSCD samplesSimilar association
2014
Phase I Trial of Bortezomib (PS-341; NSC 681239) and “Nonhybrid” (Bolus) Infusion Schedule of Alvocidib (Flavopiridol; NSC 649890) in Patients with Recurrent or Refractory Indolent B-cell Neoplasms
Holkova B, Kmieciak M, Perkins EB, Bose P, Baz RC, Roodman GD, Stuart RK, Ramakrishnan V, Wan W, Peer CJ, Dawson J, Kang L, Honeycutt C, Tombes MB, Shrader E, Weir-Wiggins C, Wellons M, Sankala H, Hogan KT, Colevas AD, Doyle LA, Figg WD, Coppola D, Roberts JD, Sullivan D, Grant S. Phase I Trial of Bortezomib (PS-341; NSC 681239) and “Nonhybrid” (Bolus) Infusion Schedule of Alvocidib (Flavopiridol; NSC 649890) in Patients with Recurrent or Refractory Indolent B-cell Neoplasms. Clinical Cancer Research 2014, 20: 5652-5662. PMID: 25248382, PMCID: PMC4233160, DOI: 10.1158/1078-0432.ccr-14-0805.Peer-Reviewed Original ResearchConceptsDose-limiting toxicityCombination of bortezomibCommon hematologic toxicityCommon nonhematologic toxicitiesIndolent B-cell neoplasmsRefractory multiple myelomaDose-escalation designNon-Hodgkin lymphomaTotal response rateB-cell malignanciesB-cell neoplasmsPharmacodynamic study resultsNonhematologic toxicitySchedule regimenStable diseaseComplete remissionHematologic toxicityPartial remissionClinical responseInvestigator's discretionDosing regimenI trialPharmacokinetic findingsSensory neuropathyInfusion schedule
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 objectivePhase I trial of bortezomib and dacarbazine in melanoma and soft tissue sarcoma
Poklepovic A, Youseffian L, Winning M, Birdsell CA, Crosby NA, Ramakrishnan V, Ernstoff MS, Roberts JD. Phase I trial of bortezomib and dacarbazine in melanoma and soft tissue sarcoma. Investigational New Drugs 2013, 31: 937-942. PMID: 23315028, PMCID: PMC3844155, DOI: 10.1007/s10637-012-9913-8.Peer-Reviewed Original ResearchConceptsSoft tissue sarcomasPhase I trialTissue sarcomasPartial responseI trialPhase II dosesDurable complete responseAmine precursor uptakeTwenty-eight patientsProteasome inhibitor bortezomibHuman melanoma cell linesMurine xenograft tumor modelXenograft tumor modelCKIT mutationsDecarboxylation (APUD) tumorsProphylactic antiemeticsRECIST v1.0Eight patientsComplete responseMelanoma cell linesWeekly dosesDose escalationAgent dacarbazinePreclinical studiesDose levels
2012
Phase I trial of the combination of flavopiridol and imatinib mesylate in patients with Bcr-Abl+ hematological malignancies
Bose P, Perkins EB, Honeycut C, Wellons MD, Stefan T, Jacobberger JW, Kontopodis E, Beumer JH, Egorin MJ, Imamura CK, Douglas Figg W, Karp JE, Koc ON, Cooper BW, Luger SM, Colevas AD, Roberts JD, Grant S. Phase I trial of the combination of flavopiridol and imatinib mesylate in patients with Bcr-Abl+ hematological malignancies. Cancer Chemotherapy And Pharmacology 2012, 69: 1657-1667. PMID: 22349810, PMCID: PMC3365614, DOI: 10.1007/s00280-012-1839-5.Peer-Reviewed Original ResearchConceptsTyrosine kinase inhibitorsCombination of flavopiridolStable diseasePhase I dose-escalation studyPhiladelphia chromosome-positive acute leukemiaSecond-generation BCR-ABL tyrosine kinase inhibitorBone marrow blast countI dose-escalation studyBCR-ABL tyrosine kinase inhibitorsKinase inhibitorsImatinib-resistant diseaseIntravenous infusion weeklyPhase II dosesDose-escalation studyMarrow blast countPhase I trialNovel combination regimenMajor pharmacokinetic interactionsBCR-ABL tyrosine kinaseChronic myelogenous leukemiaInfusion weeklyCyclin-dependent kinase inhibitorBlast countCombination regimenComplete response