2018
Duvelisib, an oral dual PI3K‐δ, γ inhibitor, shows clinical activity in indolent non‐Hodgkin lymphoma in a phase 1 study
Flinn IW, Patel M, Oki Y, Horwitz S, Foss FF, Allen K, Douglas M, Stern H, Sweeney J, Kharidia J, Kelly P, Kelly VM, Kahl B. Duvelisib, an oral dual PI3K‐δ, γ inhibitor, shows clinical activity in indolent non‐Hodgkin lymphoma in a phase 1 study. American Journal Of Hematology 2018, 93: 1311-1317. PMID: 30033575, PMCID: PMC6220789, DOI: 10.1002/ajh.25228.Peer-Reviewed Original ResearchConceptsIndolent non-Hodgkin lymphomaDose-limiting toxicityNon-Hodgkin lymphomaClinical activityINHL patientsHematologic malignanciesClinical developmentGrade 3 transaminase elevationMedian progression-free survivalOral dual inhibitorAcute respiratory failureE. coli sepsisElevated liver enzymesOpen-label studyAcceptable safety profileAdvanced hematologic malignanciesDose-escalation phaseGrade 3 rashProgression-free survivalSevere adverse eventsPhase 1 studyDuration of responseFavorable clinical activityFurther clinical developmentBID cohortA Phase I Dose‐Escalation Study of Clofarabine in Patients with Relapsed or Refractory Low‐Grade or Intermediate‐Grade B‐Cell or T‐Cell Lymphoma
Foss FM, Parker T. A Phase I Dose‐Escalation Study of Clofarabine in Patients with Relapsed or Refractory Low‐Grade or Intermediate‐Grade B‐Cell or T‐Cell Lymphoma. The Oncologist 2018, 23: 397-e30. PMID: 29438091, PMCID: PMC5896711, DOI: 10.1634/theoncologist.2017-0658.Peer-Reviewed Original ResearchConceptsCutaneous T-cell lymphomaT-cell lymphomaNon-Hodgkin lymphomaOverall response rateIntermediate-grade B-cellB cellsPartial responseResponse ratePhase I dose-escalation studyRefractory acute lymphoblastic leukemiaI dose-escalation studyT-cell non-Hodgkin lymphomaB-cell non-Hodgkin lymphomaPositron emission tomography scanSecond-generation purine nucleoside analogAggressive B-cell lymphomasPhase IDose of clofarabineGrade 3 leukopeniaLow-dose cohortMinimal hematologic toxicityRefractory acute leukemiaRefractory low gradeRefractory lymphoid malignanciesSingle-agent rituximab
2017
Activity of the PI3K-δ,γ inhibitor duvelisib in a phase 1 trial and preclinical models of T-cell lymphoma
Horwitz SM, Koch R, Porcu P, Oki Y, Moskowitz A, Perez M, Myskowski P, Officer A, Jaffe JD, Morrow SN, Allen K, Douglas M, Stern H, Sweeney J, Kelly P, Kelly V, Aster JC, Weaver D, Foss FM, Weinstock DM. Activity of the PI3K-δ,γ inhibitor duvelisib in a phase 1 trial and preclinical models of T-cell lymphoma. Blood 2017, 131: 888-898. PMID: 29233821, PMCID: PMC5824337, DOI: 10.1182/blood-2017-08-802470.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, OralAdultAgedAged, 80 and overClass I Phosphatidylinositol 3-KinasesClass Ib Phosphatidylinositol 3-KinaseFemaleHumansIsoquinolinesLymphoma, T-Cell, CutaneousLymphoma, T-Cell, PeripheralMaleMaximum Tolerated DoseMiddle AgedPhosphoinositide-3 Kinase InhibitorsPrognosisPurinesSafetySkin NeoplasmsTissue DistributionConceptsT-cell lymphomaPhospho-AktImmunosuppressive M2-like phenotypeCutaneous T-cell lymphomaNonmalignant immune cellsOpen-label studySerum cytokine profilesAcceptable safety profileImmune-mediated effectsPhase 1 trialOverall response rateM1-like phenotypePatient-derived xenograftsTumor-associated macrophagesM2-like phenotypeInflammatory M1-like phenotypeT cell growthRefractory PTCLTransaminase increaseAdverse eventsClinical responseCytokine profileMaculopapular rashComplete responsePreclinical evidenceDuvelisib, a novel oral dual inhibitor of PI3K-δ,γ, is clinically active in advanced hematologic malignancies
Flinn IW, O'Brien S, Kahl B, Patel M, Oki Y, Foss FF, Porcu P, Jones J, Burger JA, Jain N, Kelly VM, Allen K, Douglas M, Sweeney J, Kelly P, Horwitz S. Duvelisib, a novel oral dual inhibitor of PI3K-δ,γ, is clinically active in advanced hematologic malignancies. Blood 2017, 131: 877-887. PMID: 29191916, PMCID: PMC6033052, DOI: 10.1182/blood-2017-05-786566.Peer-Reviewed Original ResearchConceptsT-cell lymphomaChronic lymphocytic leukemiaIndolent non-Hodgkin lymphomaOral dual inhibitorAdvanced hematologic malignanciesComplete responseTransaminase increaseHematologic malignanciesRefractory chronic lymphocytic leukemiaPeripheral T-cell lymphomaCutaneous T-cell lymphomaAlanine transaminase increaseHematologic malignancy treatmentDose-escalation phaseSevere adverse eventsPhase 1 studyDual inhibitorOverall response rateLate-stage clinical developmentNon-Hodgkin lymphomaCLL tumor cellsRange of dosesAdverse eventsClinical responseMedian time
2015
Phase 1/2 study of mogamulizumab, a defucosylated anti-CCR4 antibody, in previously treated patients with cutaneous T-cell lymphoma
Duvic M, Pinter-Brown LC, Foss FM, Sokol L, Jorgensen JL, Challagundla P, Dwyer KM, Zhang X, Kurman MR, Ballerini R, Liu L, Kim YH. Phase 1/2 study of mogamulizumab, a defucosylated anti-CCR4 antibody, in previously treated patients with cutaneous T-cell lymphoma. Blood 2015, 125: 1883-1889. PMID: 25605368, PMCID: PMC4375715, DOI: 10.1182/blood-2014-09-600924.Peer-Reviewed Original ResearchConceptsCutaneous T-cell lymphomaEfficacy of mogamulizumabT-cell lymphomaAnti-CC chemokine receptor 4 monoclonal antibodyFrequent treatment-emergent adverse eventsCutaneous T-cell lymphoma patientsTreatment-emergent adverse eventsT-cell lymphoma patientsSignificant hematologic effectsInfusion-related reactionsPhase 1/2 studyOverall response ratePhase 3 investigationAnti-CCR4 antibodyEvaluable patientsBlood involvementAdverse eventsGrade 1/2Sézary syndromeComplete responseMycosis fungoidesLymphoma patientsHematologic effectsDisease progressionMogamulizumab
2007
Phase IIB Multicenter Trial of Vorinostat in Patients With Persistent, Progressive, or Treatment Refractory Cutaneous T-Cell Lymphoma
Olsen EA, Kim YH, Kuzel TM, Pacheco TR, Foss FM, Parker S, Frankel SR, Chen C, Ricker JL, Arduino JM, Duvic M. Phase IIB Multicenter Trial of Vorinostat in Patients With Persistent, Progressive, or Treatment Refractory Cutaneous T-Cell Lymphoma. Journal Of Clinical Oncology 2007, 25: 3109-3115. PMID: 17577020, DOI: 10.1200/jco.2006.10.2434.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, OralAdultAgedAged, 80 and overConfidence IntervalsDose-Response Relationship, DrugDrug Administration ScheduleDrug Resistance, NeoplasmFemaleFollow-Up StudiesHumansHydroxamic AcidsLymphoma, T-Cell, CutaneousMaleMaximum Tolerated DoseMiddle AgedNeoplasm StagingProbabilitySalvage TherapySkin NeoplasmsSurvival AnalysisTreatment OutcomeVorinostatConceptsObjective response rateDuration of responseMF/SSStage IIBAdverse experiencesOral vorinostatPruritus reliefHigh patientCommon drug-related adverse experiencesRefractory cutaneous T-cell lymphomaMedian DORDrug-related adverse experiencesCutaneous T-cell lymphomaEnd pointT-cell lymphoma subtypesPrior systemic therapyStage IIB diseasePrimary end pointSecondary end pointsAcceptable safety profileHistone deacetylase inhibitor vorinostatPhase IIb trialT-cell lymphomaRecurrent mycosis fungoidesIIB disease