2024
Safety and activity of CTX130, a CD70-targeted allogeneic CRISPR-Cas9-engineered CAR T-cell therapy, in patients with relapsed or refractory T-cell malignancies (COBALT-LYM): a single-arm, open-label, phase 1, dose-escalation study
Iyer S, Sica R, Ho P, Prica A, Zain J, Foss F, Hu B, Beitinjaneh A, Weng W, Kim Y, Khodadoust M, Huen A, Williams L, Ma A, Huang E, Ganpule A, Nagar S, Sripakdeevong P, Cullingford E, Karnik S, Dequeant M, Patel J, He X, Li Z, He Q, Mendonez J, Keegan A, Horwitz S. Safety and activity of CTX130, a CD70-targeted allogeneic CRISPR-Cas9-engineered CAR T-cell therapy, in patients with relapsed or refractory T-cell malignancies (COBALT-LYM): a single-arm, open-label, phase 1, dose-escalation study. The Lancet Oncology 2024 PMID: 39617017, DOI: 10.1016/s1470-2045(24)00508-4.Peer-Reviewed Original ResearchT-cell lymphomaPeripheral T-cell lymphomaCutaneous T-cell lymphomaRefractory T-cell lymphomaEastern Cooperative Oncology GroupChimeric antigen receptorCytokine release syndromeCAR+ T cellsSerious adverse eventsAdverse eventsT cellsOpen-labelRefractory peripheral T-cell lymphomaAllogeneic chimeric antigen receptorHealthy donor T cellsRefractory T-cell malignanciesCAR-T cell therapyMedian patient follow-upIncidence of adverse eventsDonor T cellsObjective response rateSystemic therapy linesDose-limiting toxicityT-cell therapyDose-escalation studyReal World Data on Efficacy and Safety of EPOCH in T-Cell Lymphoma
Straining R, Foss F, Schiffer M, Amin K, Agarwal S, Isufi I, Huntington S, Kothari S, Seropian S, Girardi M, Sethi T. Real World Data on Efficacy and Safety of EPOCH in T-Cell Lymphoma. Clinical Lymphoma Myeloma & Leukemia 2024 PMID: 39368885, DOI: 10.1016/j.clml.2024.09.005.Peer-Reviewed Original ResearchT-cell lymphomaHeterogeneous group of lymphoid malignanciesGroup of lymphoid malignanciesPeripheral T-cell lymphomaAggressive T-cell lymphomaCutaneous T-cell lymphomaT cellsResponse rateR/R settingComplete responseLymphoid malignanciesPoor outcomeAnaplastic large cell lymphomaFrontline treatment regimensLarge cell lymphomaCombination of prednisoneHeterogeneous groupCell lymphomaChemotherapy optionsCaucasian patientsFirst-linePositive patientsTreatment regimensGrade 3LymphomaPhase 2 trial of the farnesyltransferase inhibitor tipifarnib for relapsed/refractory peripheral T-cell lymphoma
Witzig T, Sokol L, Kim W, de la Cruz Vicente F, García-Sancho A, Advani R, Vidal J, de Oña Navarrete R, Marin-Niebla A, Izquierdo A, Terol M, Domingo-Domenech E, Saunders A, Bendris N, Mackey J, Leoni M, Foss F. Phase 2 trial of the farnesyltransferase inhibitor tipifarnib for relapsed/refractory peripheral T-cell lymphoma. Blood Advances 2024, 8: 4581-4592. PMID: 38991123, PMCID: PMC11401221, DOI: 10.1182/bloodadvances.2024012806.Peer-Reviewed Original ResearchRelapsed/refractory peripheral T-cell lymphomaAngioimmunoblastic T-cell lymphomaPeripheral T-cell lymphomaT-cell lymphomaProgression-free survivalDuration of responseAdverse eventsAngioimmunoblastic T-cell lymphoma patientsMedian duration of responseMedian progression-free survivalSafety of tipifarnibHematologic adverse eventsMedian overall survivalTreatment-related deathsBiomarkers of responsePhase 2 trialSixty-five patientsFarnesyltransferase inhibitor tipifarnibNon-responder groupTumor mutational profileSingle-arm trialPTCL-NOSOpen-labelOverall survivalPrimary endpoint
2023
Valemetostat for Relapsed or Refractory Peripheral T-Cell Lymphomas: Primary Results from a Phase 1 Trial
Jacobsen E, Maruyama D, Porcu P, Tobinai K, Allen P, Ishitsuka K, Tsukasaki K, Kusumoto S, Foss F, Yamauchi N, Morishima S, Imaizumi Y, Izutsu K, Feldman T, Kawamata T, Kakurai Y, Yamauchi H, Biserna N, Inoue A, Tsutsumi S, Horwitz S. Valemetostat for Relapsed or Refractory Peripheral T-Cell Lymphomas: Primary Results from a Phase 1 Trial. Blood 2023, 142: 303. DOI: 10.1182/blood-2023-172512.Peer-Reviewed Original ResearchPeripheral T-cell lymphomaAdult T-cell leukemia/lymphomaT-cell non-Hodgkin lymphomaObjective response rateDuration of responseProgression-free survivalT-cell lymphomaMedian DORATLL groupPTCL groupData cutoffAdverse eventsClinical activityResponse rateRefractory peripheral T-cell lymphomaMedian progression-free survivalAngioimmunoblastic T-cell lymphomaT-cell leukemia/lymphomaDose-expansion cohortsDose-expansion phaseMedian prior therapiesPreliminary efficacy assessmentComplete response rateDose-escalation phasePhase 2 trial
2022
Age, Albumin, and LDH Predict Outcome of Patients with Limited Stage Peripheral T Cell Lymphoma: A Prognostic Model Developed on 244 Cases Enrolled in the T Cell Project 1 By the International T Cell Project Network
Hapgood G, Civallero M, Stepanishyna Y, Vose J, Cabrera M, Advani R, Pileri S, Manni M, Horwitz S, Foss F, Hitz F, Radford J, Dlouhy I, Chiattone C, Kim W, Skrypets T, Nagler A, Trotman J, Luminari S, Federico M. Age, Albumin, and LDH Predict Outcome of Patients with Limited Stage Peripheral T Cell Lymphoma: A Prognostic Model Developed on 244 Cases Enrolled in the T Cell Project 1 By the International T Cell Project Network. Blood 2022, 140: 1476-1478. DOI: 10.1182/blood-2022-158883.Peer-Reviewed Original ResearchComparative efficacy and tolerability of novel agents vs chemotherapy in relapsed and refractory T-cell lymphomas: a meta-analysis
Shafagati N, Koh M, Boussi L, Park H, Stuver R, Bain P, Foss FM, Shen C, Jain S. Comparative efficacy and tolerability of novel agents vs chemotherapy in relapsed and refractory T-cell lymphomas: a meta-analysis. Blood Advances 2022, 6: 4740-4762. PMID: 35816645, PMCID: PMC9631658, DOI: 10.1182/bloodadvances.2022007425.Peer-Reviewed Original ResearchConceptsPeripheral T-cell lymphomaOverall response rateR Peripheral T Cell LymphomaCombination chemotherapyT-cell lymphomaSingle agentComparative efficacyRefractory T-cell lymphomaPhase ISingle-agent strategyPhase II trialPlatinum-based regimensPhase III trialsPhase I trialOptimal treatment strategyNovel single agentsRandom-effects modelSignificant subgroup differencesII trialIII trialsI trialHistological subtypesTreatment paradigmClinical trialsDrug classesS217: PRELIMINARY ANALYSIS OF THE PHASE II STUDY USING TOLINAPANT (ASTX660) MONOTHERAPY IN 98 PERIPHERAL T‐CELL LYMPHOMA AND 51 CUTANEOUS T‐CELL LYMPHOMA SUBJECTS WITH RELAPSED REFRACTORY DISEASE.
Michot J, Mehta A, Samaniego F, Bachy E, Zinzani P, Prica A, Colins G, Ribrag V, Wagner‐Johnston N, El‐Sharkawi D, O'Connor O, Wilcox R, Wang L, Wilson L, Sims M, Taylor J, Keer H, Foss F. S217: PRELIMINARY ANALYSIS OF THE PHASE II STUDY USING TOLINAPANT (ASTX660) MONOTHERAPY IN 98 PERIPHERAL T‐CELL LYMPHOMA AND 51 CUTANEOUS T‐CELL LYMPHOMA SUBJECTS WITH RELAPSED REFRACTORY DISEASE. HemaSphere 2022, 6: 118-119. DOI: 10.1097/01.hs9.0000843760.14993.43.Peer-Reviewed Original ResearchPeripheral Blood Involvement at Staging in Patients With Aggressive Peripheral T-Cell Lymphoma
Avery J, Chandhok N, Rainey C, Torres R, Huntington S, Isufi I, Seropian S, Xu ML, Foss F. Peripheral Blood Involvement at Staging in Patients With Aggressive Peripheral T-Cell Lymphoma. Clinical Lymphoma Myeloma & Leukemia 2022, 22: 680-689. PMID: 35568635, DOI: 10.1016/j.clml.2022.04.019.Peer-Reviewed Original ResearchConceptsPeripheral T-cell lymphomaT-cell lymphomaBone marrow involvementBlood involvementFlow cytometryMarrow involvementNodal subtypesAggressive peripheral T-cell lymphomaNodal T-cell lymphomasNegative flow cytometryPeripheral blood involvementPositive flow cytometryMalignant T cellsMalignant tumor cellsMedian PFSTime ofdiagnosisOverall survivalLymph nodesPoor outcomeDisease stagePeripheral bloodT cellsPrognostic measuresRare subgroupLymphomaT-Cell Lymphomas, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology.
Horwitz SM, Ansell S, Ai WZ, Barnes J, Barta SK, Brammer J, Clemens MW, Dogan A, Foss F, Ghione P, Goodman AM, Guitart J, Halwani A, Haverkos BM, Hoppe RT, Jacobsen E, Jagadeesh D, Jones A, Kallam A, Kim YH, Kumar K, Mehta-Shah N, Olsen EA, Rajguru SA, Rozati S, Said J, Shaver A, Shea L, Shinohara MM, Sokol L, Torres-Cabala C, Wilcox R, Wu P, Zain J, Dwyer M, Sundar H. T-Cell Lymphomas, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology. Journal Of The National Comprehensive Cancer Network 2022, 20: 285-308. PMID: 35276674, DOI: 10.6004/jnccn.2022.0015.Peer-Reviewed Original ResearchConceptsPeripheral T-cell lymphomaT-cell lymphomaAnaplastic large cell lymphomaLarge cell lymphomaAnaplastic lymphoma kinaseCell lymphomaLymphoma kinaseTreatment of PTCLNCCN Clinical Practice GuidelinesAngioimmunoblastic T-cell lymphomaClinical practice guidelinesNon-Hodgkin lymphomaMature T cellsNCCN guidelinesLymphoproliferative disordersCommon subtypePractice guidelinesT cellsLymphomaHeterogeneous groupGuidelinesSubtypesDiagnosisOncologySafety considerations with the current treatments for peripheral T-cell lymphoma
Sethi T, Montanari F, Foss F. Safety considerations with the current treatments for peripheral T-cell lymphoma. Expert Opinion On Drug Safety 2022, 21: 653-660. PMID: 35129014, DOI: 10.1080/14740338.2022.2036120.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsPeripheral T-cell lymphomaT-cell lymphomaCombination chemotherapyTreatment regimensAnthracycline-based combination chemotherapyNK-T cell lymphomaB-cell non-Hodgkin lymphomaSingle-agent chemotherapyAvailable treatment regimensNon-Hodgkin lymphomaT cell subtypesSelection of agentsRelapsed settingAgent chemotherapyNatural killerFrontline treatmentPoor prognosisDisease groupUnique immunobiologyCurrent treatmentCell lymphomaCell disordersSide effectsLymphomaCertain complications
2021
Comparative Analysis of Mature T-Cell and NK/T-Cell Lymphomas in Patients with and without HIV: Results from the NA-Accord and Complete Cohorts
Koh M, Merrill M, Koh M, Stuver R, Alonso C, Foss F, Mayor A, Gill M, Epeldegui M, Cachay E, Thorne J, Silverberg M, Horberg M, Atlhoff K, Nijhawan A, McGinnis K, Rabkin C, Napravnik S, Shen C, Jain S. Comparative Analysis of Mature T-Cell and NK/T-Cell Lymphomas in Patients with and without HIV: Results from the NA-Accord and Complete Cohorts. Blood 2021, 138: 1380. DOI: 10.1182/blood-2021-147837.Peer-Reviewed Original ResearchNK/T-cell lymphomaT-cell lymphomaB-cell lymphomaNA-ACCORDViral loadBurkitt's lymphomaLymphoma diagnosisCurrent antiretroviral therapy eraWorse median overall survivalPeripheral T-cell lymphomaAnaplastic large cell lymphomaLarge B-cell lymphomaAntiretroviral therapy eraBaseline clinical characteristicsMedian overall survivalMulticenter cohort studyOutcomes of patientsSpeakers bureauChronic kidney diseasePrimary CNS lymphomaYear of diagnosisCommon histological subtypeMature T-cell lymphomasSurvival of patientsLarge observational cohortEPOCH Is a Safe and Effective Treatment Option for Aggressive T-Cell Lymphomas
Sethi T, Gerstein R, Schiffer M, Amin K, Agarwal S, Foss F. EPOCH Is a Safe and Effective Treatment Option for Aggressive T-Cell Lymphomas. Blood 2021, 138: 4547. DOI: 10.1182/blood-2021-151238.Peer-Reviewed Original ResearchAggressive T-cell lymphomaCutaneous T-cell lymphomaT-cell lymphomaAnaplastic large cell lymphomaSubcutaneous panniculitis-like T-cell lymphomaAngioimmunoblastic T-cell lymphomaAdult T-cell leukemia/lymphomaProgression-free survivalOverall response rateNon-Hodgkin lymphomaResponse rateR settingOverall survivalCR rateAdverse effectsPanniculitis-like T-cell lymphomaGrade 3 adverse effectsGrade 4 adverse effectsMedian progression-free survivalAllogeneic stem cell transplantPeripheral T-cell lymphomaT-cell leukemia/lymphomaYale-New Haven HospitalFirst lineEfficacy of etoposideA Global Phase 2 Study of Valemetostat Tosylate (Valemetostat) in Patients with Relapsed or Refractory (R/R) Peripheral T-Cell Lymphoma (PTCL), Including R/R Adult T-Cell Leukemia/Lymphoma (ATL) - Valentine-PTCL01
Foss F, Porcu P, Horwitz S, Izutsu K, Ishitsuka K, Kato K, Jin J, Du Y, Inoue A. A Global Phase 2 Study of Valemetostat Tosylate (Valemetostat) in Patients with Relapsed or Refractory (R/R) Peripheral T-Cell Lymphoma (PTCL), Including R/R Adult T-Cell Leukemia/Lymphoma (ATL) - Valentine-PTCL01. Blood 2021, 138: 2533. DOI: 10.1182/blood-2021-144676.Peer-Reviewed Original ResearchR Peripheral T Cell LymphomaTreatment-emergent adverse eventsPeripheral T-cell lymphomaALK-positive anaplastic large cell lymphomaT-cell lymphomaNon-Hodgkin lymphomaPhase 2 studyOverall response rateKyowa Hakko KirinPersonal feesCohort 1Current equity holderDaiichi SankyoResponse rateSeattle GeneticsOno PharmaceuticalCohort 2Computed tomographyMonomorphic epitheliotropic intestinal T-cell lymphomaActive central nervous system (CNS) involvementADC therapeuticsSerious treatment-emergent adverse eventsRefractory peripheral T-cell lymphomaNodal peripheral T-cell lymphomaAllogeneic hematopoietic cell transplantFinal Results from a Phase 2 Study of Tipifarnib in Subjects with Relapsed or Refractory Peripheral T-Cell Lymphoma
Witzig T, Sokol L, Kim W, de la Cruz Vicente F, Caballero D, Advani R, de Oña R, Niebla A, Terol M, Eva D, Bendris N, Ahsan J, Leoni M, Foss F. Final Results from a Phase 2 Study of Tipifarnib in Subjects with Relapsed or Refractory Peripheral T-Cell Lymphoma. Blood 2021, 138: 621. DOI: 10.1182/blood-2021-147279.Peer-Reviewed Original ResearchAngioimmunoblastic T-cell lymphomaProgression-free survivalOverall response rateT-cell lymphomaOverall survivalPeripheral T-cell lymphomaT-cell non-Hodgkin lymphomaOpen-label trialPhase 2 studyNegative prognostic factorDuration of responsePotential predictive biomarkersNon-Hodgkin lymphomaT-cell homingProgression of diseasePTCL patientsRefractory PTCLUnacceptable toxicityAdult patientsPrognostic factorsPredictive biomarkersLugano classificationCXCL12 expressionReceptor CXCR4New therapiesBelinostat in combination with standard cyclophosphamide, doxorubicin, vincristine and prednisone as first-line treatment for patients with newly diagnosed peripheral T-cell lymphoma
Johnston PB, Cashen AF, Nikolinakos PG, Beaven AW, Barta SK, Bhat G, Hasal SJ, De Vos S, Oki Y, Deng C, Foss FM. Belinostat in combination with standard cyclophosphamide, doxorubicin, vincristine and prednisone as first-line treatment for patients with newly diagnosed peripheral T-cell lymphoma. Experimental Hematology & Oncology 2021, 10: 15. PMID: 33602316, PMCID: PMC7893947, DOI: 10.1186/s40164-021-00203-8.Peer-Reviewed Original ResearchPeripheral T-cell lymphomaOverall response rateT-cell lymphomaAdverse eventsDay 1Untreated peripheral T-cell lymphomaRefractory peripheral T-cell lymphomaMedian relative dose intensityPatient experienced DLTSafety/tolerabilityRelative dose intensityResultsTwenty-three patientsSerious adverse eventsFirst-line treatmentHistone deacetylase inhibitorsExperienced DLTsFebrile neutropeniaStandard CHOPStandard cyclophosphamideDose intensityAdditional patientsMTD doseCHOP combinationPK parametersSame dose
2020
Weekly Dosing Schedule of Brentuximab Vedotin in Mycosis Fungoides/Sezary Syndrome and Aggressive T Cell Lymphomas
Lee M, Schiffer M, Isufi I, Huntington S, Xu M, Seropian S, Gowda L, Kothari S, Girardi M, Foss F. Weekly Dosing Schedule of Brentuximab Vedotin in Mycosis Fungoides/Sezary Syndrome and Aggressive T Cell Lymphomas. Blood 2020, 136: 21-22. DOI: 10.1182/blood-2020-139790.Peer-Reviewed Original ResearchT-cell lymphomaAggressive T-cell lymphomaWeekly dosing scheduleMycosis fungoides/Sezary syndromeMF/SSWeekly dosingCell lymphomaDosing schedulesBrentuximab vedotinSezary syndromeGamma-delta T-cell lymphomaWeekly scheduleNK-T cell lymphomaAngioimmunoblastic T-cell lymphomaPeripheral T-cell lymphomaAnaplastic large cell lymphomaCancer response rateIncidence of neuropathyWeekly x 3Prospective clinical trialsStem cell transplantAdult T-cell leukemiaLarge cell lymphomaT-cell leukemiaDose weekly
2019
Outcomes for Relapsed and Refractory Peripheral T-Cell Lymphoma Patients after Front-Line Therapy from the COMPLETE Registry
Lansigan F, Horwitz SM, Pinter-Brown LC, Rosen ST, Pro B, Hsi ED, Federico M, Gisselbrecht C, Schwartz M, Bellm LA, Acosta M, Shustov AR, Advani RH, Feldman T, Lechowicz MJ, Smith SM, Tulpule A, Craig MD, Greer JP, Kahl BS, Leach JW, Morganstein N, Casulo C, Park SI, Foss FM. Outcomes for Relapsed and Refractory Peripheral T-Cell Lymphoma Patients after Front-Line Therapy from the COMPLETE Registry. Acta Haematologica 2019, 143: 40-50. PMID: 31315113, DOI: 10.1159/000500666.Peer-Reviewed Original ResearchConceptsPeripheral T-cell lymphomaFront-line therapyComplete responseRelapsed diseaseT-cell lymphomaRefractory patientsInitial treatmentPrimary refractoryOverall survivalPeripheral T-cell lymphoma patientsResponse/stable diseaseT-cell lymphoma patientsAggressive T-cell lymphomaSingle-agent regimensDays of enrollmentObjective response ratePrimary refractory diseaseSecond-line settingSecond-line therapyActive single agentProspective outcome dataSingle-agent therapyLonger overall survivalUnmet medical needGood responseEffect of leucovorin administration on mucositis and skin reactions in patients with peripheral T-cell lymphoma or cutaneous T-cell lymphoma treated with pralatrexate*
Foss FM, Parker TL, Girardi M, Li A. Effect of leucovorin administration on mucositis and skin reactions in patients with peripheral T-cell lymphoma or cutaneous T-cell lymphoma treated with pralatrexate*. Leukemia & Lymphoma 2019, 60: 2927-2930. PMID: 31119966, DOI: 10.1080/10428194.2019.1612061.Peer-Reviewed Original ResearchConceptsPeripheral T-cell lymphomaCutaneous T-cell lymphomaT-cell lymphomaIncidence of mucositisAddition of leucovorinSkin reactionsLeucovorin administrationMucositis incidenceMucositis occurrenceDisease stabilizationAdverse eventsClinical responseCTCL patientsPoor prognosisLeucovorinMucositisPatientsResponse rateLymphomaPralatrexateIncidenceEfficacyPrognosisDosingAdministrationSingle agents vs combination chemotherapy in relapsed and refractory peripheral T‐cell lymphoma: Results from the comprehensive oncology measures for peripheral T‐cell lymphoma treatment (COMPLETE) registry
Stuver RN, Khan N, Schwartz M, Acosta M, Federico M, Gisselbrecht C, Horwitz SM, Lansigan F, Pinter‐Brown L, Pro B, Shustov AR, Foss FM, Jain S. Single agents vs combination chemotherapy in relapsed and refractory peripheral T‐cell lymphoma: Results from the comprehensive oncology measures for peripheral T‐cell lymphoma treatment (COMPLETE) registry. American Journal Of Hematology 2019, 94: 641-649. PMID: 30896890, PMCID: PMC7928240, DOI: 10.1002/ajh.25463.Peer-Reviewed Original ResearchConceptsPeripheral T-cell lymphomaRefractory peripheral T-cell lymphomaComprehensive Oncology MeasuresT-cell lymphomaCombination chemotherapyFirst retreatmentSingle agentCombination therapyR diseaseTreatment RegistryEligibility criteriaR Peripheral T Cell LymphomaHematopoietic stem cell transplantationPrior systemic therapyComplete response rateMedian overall survivalProgression-free survivalStem cell transplantationPrimary endpointAdverse eventsOverall survivalSystemic therapyMore patientsRandomized trialsGrade 3Randomized Phase III Study of Alisertib or Investigator’s Choice (Selected Single Agent) in Patients With Relapsed or Refractory Peripheral T-Cell Lymphoma
O’Connor O, Özcan M, Jacobsen ED, Roncero JM, Trotman J, Demeter J, Masszi T, Pereira J, Ramchandren R, Beaven A, Caballero D, Horwitz SM, Lennard A, Turgut M, Hamerschlak N, d’Amore F, Foss F, Kim WS, Leonard JP, Zinzani PL, Chiattone CS, Hsi ED, Trümper L, Liu H, Sheldon-Waniga E, Ullmann CD, Venkatakrishnan K, Leonard EJ, Shustov AR, . Randomized Phase III Study of Alisertib or Investigator’s Choice (Selected Single Agent) in Patients With Relapsed or Refractory Peripheral T-Cell Lymphoma. Journal Of Clinical Oncology 2019, 37: 613-623. PMID: 30707661, PMCID: PMC6494247, DOI: 10.1200/jco.18.00899.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic AgentsAurora Kinase AAzepinesDisease ProgressionDisease-Free SurvivalDrug Resistance, NeoplasmEarly Termination of Clinical TrialsFemaleHumansLymphoma, T-Cell, PeripheralMaleMiddle AgedProtein Kinase InhibitorsPyrimidinesRecurrenceTime FactorsYoung AdultConceptsPeripheral T-cell lymphomaRefractory peripheral T-cell lymphomaProgression-free survivalOverall response rateT-cell lymphomaComparator armInvestigational Aurora A kinase inhibitorResponse rateMedian progression-free survivalTwo-year overall survivalRandomized phase III studyRandomized phase III trialIndependent data monitoring committeeEfficacy of alisertibMore prior therapiesSingle-agent comparatorCommon adverse eventsPhase III studyPhase III trialsIndependent central reviewData monitoring committeeDrug discontinuationIntravenous romidepsinOral alisertibPrior therapy