2020
Mogamulizumab in Combination with Durvalumab or Tremelimumab in Patients with Advanced Solid Tumors: A Phase I Study
Zamarin D, Hamid O, Nayak-Kapoor A, Sahebjam S, Sznol M, Collaku A, Fox FE, Marshall MA, Hong DS. Mogamulizumab in Combination with Durvalumab or Tremelimumab in Patients with Advanced Solid Tumors: A Phase I Study. Clinical Cancer Research 2020, 26: 4531-4541. PMID: 32586937, PMCID: PMC8375360, DOI: 10.1158/1078-0432.ccr-20-0328.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic Agents, ImmunologicalAntineoplastic Combined Chemotherapy ProtocolsDose-Response Relationship, DrugFemaleHumansLymphocyte DepletionMaleMiddle AgedNeoplasm StagingPancreatic NeoplasmsReceptors, CCR4T-Lymphocytes, RegulatoryYoung AdultConceptsAdvanced solid tumorsDose escalationSolid tumorsCohort expansionEffector regulatory T cellsC chemokine receptor 4Phase IDose-expansion cohortsAdvanced pancreatic cancerObjective response rateMajority of patientsRegulatory T cellsChemokine receptor 4Potent antitumor efficacyMogamulizumab treatmentCheckpoint inhibitorsDose expansionExpansion cohortIntratumoral TregsPrimary endpointClinical responseEscalation studyBaseline degreePharmacodynamic profilePancreatic cancer
2007
A Phase I study of the novel ribonucleotide reductase inhibitor 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, Triapine®) in combination with the nucleoside analog fludarabine for patients with refractory acute leukemias and aggressive myeloproliferative disorders
Karp JE, Giles FJ, Gojo I, Morris L, Greer J, Johnson B, Thein M, Sznol M, Low J. A Phase I study of the novel ribonucleotide reductase inhibitor 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, Triapine®) in combination with the nucleoside analog fludarabine for patients with refractory acute leukemias and aggressive myeloproliferative disorders. Leukemia Research 2007, 32: 71-77. PMID: 17640728, PMCID: PMC2726775, DOI: 10.1016/j.leukres.2007.05.003.Peer-Reviewed Original ResearchConceptsAggressive myeloproliferative disorderDaily x 5Refractory acute leukemiaMyeloproliferative disordersAcute leukemiaRibonucleotide reductase inhibitorReductase inhibitorsDays of fludarabineRefractory myeloid malignanciesPhase I trialDrug-related toxicityNovel ribonucleotide reductase inhibitorNucleoside analog fludarabinePotent ribonucleotide reductase inhibitorPartial responseI trialMetabolic acidosisSchedule AFludarabineMyeloid malignanciesPatientsPhase ILeukemiaDisordersInhibitorsPhase I and pharmacokinetic study of Triapine®, a potent ribonucleotide reductase inhibitor, in adults with advanced hematologic malignancies
Gojo I, Tidwell ML, Greer J, Takebe N, Seiter K, Pochron MF, Johnson B, Sznol M, Karp JE. Phase I and pharmacokinetic study of Triapine®, a potent ribonucleotide reductase inhibitor, in adults with advanced hematologic malignancies. Leukemia Research 2007, 31: 1165-1173. PMID: 17324462, DOI: 10.1016/j.leukres.2007.01.004.Peer-Reviewed Original ResearchConceptsHematologic malignanciesDay 1White blood cell countPhase IAdvanced hematologic malignanciesBlood cell countPeak plasma concentrationPre-clinical modelsAnti-leukemia activityPotent ribonucleotide reductase inhibitorWarrants further investigationAdvanced leukemiaH infusionPlasma concentrationsDose levelsRibonucleotide reductase inhibitorCell countReductase inhibitorsPharmacokinetic studyMalignancyGrowth inhibitionFurther investigationPotent inhibitorAdultsDays
2006
Triapine and cytarabine is an active combination in patients with acute leukemia or myelodysplastic syndrome
Yee KW, Cortes J, Ferrajoli A, Garcia-Manero G, Verstovsek S, Wierda W, Thomas D, Faderl S, King I, O’Brien S, Jeha S, Andreeff M, Cahill A, Sznol M, Giles FJ. Triapine and cytarabine is an active combination in patients with acute leukemia or myelodysplastic syndrome. Leukemia Research 2006, 30: 813-822. PMID: 16478631, DOI: 10.1016/j.leukres.2005.12.013.Peer-Reviewed Original ResearchMeSH KeywordsAcute DiseaseAdolescentAdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsCytarabineDose-Response Relationship, DrugDrug Administration ScheduleDrug CombinationsFemaleHumansInjections, IntravenousLeukemia, MyeloidMaleMaximum Tolerated DoseMiddle AgedMyelodysplastic SyndromesPyridinesRecurrenceRisk FactorsThiosemicarbazonesTreatment OutcomeConceptsAra-C dose levelsDose levelsM2/dayAcute leukemiaSignificant anti-leukemia activityConsecutive daysPhase II regimenRefractory acute leukemiaHigh-risk MDSAnti-leukemia activityEvaluable patientsMyelodysplastic syndromeActive combinationPatientsPhase IIron chelatorsLeukemiaAraPotent inhibitorDaysTriapineRegimenCytarabineInfusionSyndrome
2005
Systemic Administration of an Attenuated, Tumor-Targeting Salmonella typhimurium to Dogs with Spontaneous Neoplasia: Phase I Evaluation
Thamm DH, Kurzman ID, King I, Li Z, Sznol M, Dubielzig RR, Vail DM, MacEwen EG. Systemic Administration of an Attenuated, Tumor-Targeting Salmonella typhimurium to Dogs with Spontaneous Neoplasia: Phase I Evaluation. Clinical Cancer Research 2005, 11: 4827-4834. PMID: 16000580, DOI: 10.1158/1078-0432.ccr-04-2510.Peer-Reviewed Original ResearchConceptsAntitumor responseTumor tissueAntitumor activityMajor antitumor responsesTumor-bearing dogsDose-limiting toxicityInherent antitumor activitySignificant antitumor activityRefractory feverDisease stabilizationEscalation trialFirst infusionShort-term toxicityIncisional biopsyClinicopathologic variablesSystemic administrationTumor targeting capacityMalignant tumorsAcute deathSpontaneous tumorsSpontaneous neoplasiaPowerful anticancer therapySalmonella typhimuriumVital signsPhase I
2004
A Phase I and Pharmacokinetic Study of VNP40101M, a Novel Sulfonylhydrazine Alkylating Agent, in Patients with Refractory Leukemia
Giles F, Thomas D, Garcia-Manero G, Faderl S, Cortes J, Verstovsek S, Ferrajoli A, Jeha S, Beran M, Koller C, Andreeff M, Cahill A, Clairmont C, Sznol M, Kantarjian H. A Phase I and Pharmacokinetic Study of VNP40101M, a Novel Sulfonylhydrazine Alkylating Agent, in Patients with Refractory Leukemia. Clinical Cancer Research 2004, 10: 2908-2917. PMID: 15131024, DOI: 10.1158/1078-0432.ccr-03-0738.Peer-Reviewed Original ResearchConceptsMaximum-tolerated doseAcute myeloid leukemiaMyelodysplastic syndromeVNP40101MExtramedullary toxicityMyeloid leukemiaDay 1Poor‐risk myelodysplastic syndromesAntileukemic activityPhase IMinimal extramedullary toxicitySignificant extramedullary toxicityFrequent adverse eventsPhase II doseInfusion-related toxicityPharmacokinetic studyCourse of treatmentSignificant antileukemic activityBroad antitumor activityNovel sulfonylhydrazineComplete remissionStarting doseAdverse eventsRefractory diseaseRefractory leukemia
2003
Phase I and pharmacodynamic study of Triapine®, a novel ribonucleotide reductase inhibitor, in patients with advanced leukemia
Giles FJ, Fracasso PM, Kantarjian HM, Cortes JE, Brown RA, Verstovsek S, Alvarado Y, Thomas DA, Faderl S, Garcia-Manero G, Wright LP, Samson T, Cahill A, Lambert P, Plunkett W, Sznol M, DiPersio JF, Gandhi V. Phase I and pharmacodynamic study of Triapine®, a novel ribonucleotide reductase inhibitor, in patients with advanced leukemia. Leukemia Research 2003, 27: 1077-1083. PMID: 12921943, DOI: 10.1016/s0145-2126(03)00118-8.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overDeoxyadenine NucleotidesDeoxyguanine NucleotidesDNADNA, NeoplasmEnzyme InhibitorsFemaleHumansInfusions, IntravenousLeukemia, LymphoidLeukemia, Myelogenous, Chronic, BCR-ABL PositiveLeukocyte CountMaleMiddle AgedPyridinesRibonucleotide ReductasesSafetyThiosemicarbazonesConceptsDose-limiting toxicityNovel ribonucleotide reductase inhibitorDay 1Ribonucleotide reductase inhibitorReductase inhibitorsWhite blood cell countPhase IContinuous intravenous infusionBlood cell countWarrants further studyObjective responseRefractory leukemiaStarting doseAdvanced leukemiaIntravenous infusionH infusionSecond infusionHematologic malignanciesPlasma concentrationsPharmacodynamic studiesPharmacodynamic dataPatientsSecond courseDay 8H beginningPhase I and pharmacokinetic study of triapine, a potent ribonucleotide reductase inhibitor, administered daily for five days in patients with advanced solid tumors.
Murren J, Modiano M, Clairmont C, Lambert P, Savaraj N, Doyle T, Sznol M. Phase I and pharmacokinetic study of triapine, a potent ribonucleotide reductase inhibitor, administered daily for five days in patients with advanced solid tumors. Clinical Cancer Research 2003, 9: 4092-100. PMID: 14519631.Peer-Reviewed Original ResearchConceptsDose-limiting toxicityAdverse eventsSafety profilePhase IGrade 3Week scheduleDrug-related adverse eventsGrade 2 adverse eventsGrade 1Common nonhematological toxicitiesGrade 4 leukopeniaSingle-patient cohortsAcceptable safety profileAdvanced solid tumorsDose-escalation phaseHepatic adverse eventsPhase II trialCohort of patientsCumulative urinary recoveryLinear pharmacokinetic behaviorPotent ribonucleotide reductase inhibitorNonhematological toxicitiesII trialMean eliminationStarting dose
2002
Phase I study of the intravenous administration of attenuated Salmonella typhimurium to patients with metastatic melanoma.
Toso JF, Gill VJ, Hwu P, Marincola FM, Restifo NP, Schwartzentruber DJ, Sherry RM, Topalian SL, Yang JC, Stock F, Freezer LJ, Morton KE, Seipp C, Haworth L, Mavroukakis S, White D, MacDonald S, Mao J, Sznol M, Rosenberg SA. Phase I study of the intravenous administration of attenuated Salmonella typhimurium to patients with metastatic melanoma. Journal Of Clinical Oncology 2002, 20: 142-52. PMID: 11773163, PMCID: PMC2064865, DOI: 10.1200/jco.2002.20.1.142.Peer-Reviewed Original ResearchConceptsDose-related toxicityMetastatic melanomaAntitumor effectsTumor colonizationMetastatic renal cell carcinomaTumor necrosis factor alphaPhase IPresent phase IMaximum-tolerated doseObjective tumor regressionIntravenous bolus infusionAttenuated Salmonella typhimuriumDose-related increaseElevated alkaline phosphataseNecrosis factor alphaRenal cell carcinomaSalmonella typhimuriumPersistent bacteremiaIL-12Proinflammatory cytokinesCell carcinomaIL-6Intravenous infusionBolus infusionTumor regression