2014
Phase I/II Study of the Antibody-Drug Conjugate Glembatumumab Vedotin in Patients With Advanced Melanoma
Ott PA, Hamid O, Pavlick AC, Kluger H, Kim KB, Boasberg PD, Simantov R, Crowley E, Green JA, Hawthorne T, Davis TA, Sznol M, Hwu P. Phase I/II Study of the Antibody-Drug Conjugate Glembatumumab Vedotin in Patients With Advanced Melanoma. Journal Of Clinical Oncology 2014, 32: 3659-3666. PMID: 25267741, PMCID: PMC4879709, DOI: 10.1200/jco.2013.54.8115.Peer-Reviewed Original ResearchConceptsMaximum-tolerated doseObjective response rateGreater objective response rateGlembatumumab vedotinAdvanced melanomaGrade 3/4 treatment-related toxicitiesHuman immunoglobulin G2 monoclonal antibodyPhase I/II studyPhase II expansion cohortPromising objective response ratesEnd pointTreatment-related deathsPrimary end pointSecondary end pointsTreatment-related toxicityProgression-free survivalPhase II expansionMonomethyl auristatin E.Stable diseaseExpansion cohortII studyPartial responseDose escalationMore patientsFrequent dosing
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 leukemiaPhase I and Pharmacokinetic Study of the Ribonucleotide Reductase Inhibitor, 3-Aminopyridine-2-Carboxaldehyde Thiosemicarbazone, Administered by 96-Hour Intravenous Continuous Infusion
Wadler S, Makower D, Clairmont C, Lambert P, Fehn K, Sznol M. Phase I and Pharmacokinetic Study of the Ribonucleotide Reductase Inhibitor, 3-Aminopyridine-2-Carboxaldehyde Thiosemicarbazone, Administered by 96-Hour Intravenous Continuous Infusion. Journal Of Clinical Oncology 2004, 22: 1553-1563. PMID: 15117978, DOI: 10.1200/jco.2004.07.158.Peer-Reviewed Original ResearchConceptsDose-limiting toxicityIntravenous continuous infusionContinuous infusionPreclinical tumor model systemsPhase II dosesStabilization of diseaseHepatic adverse eventsMaximum-tolerated dosePhase II dosePhase II trialPhase I trialAccelerated titration designPharmacokinetic studySerum tumor markersSubstantial inter-patient variabilityAbnormal organ functionDetailed pharmacokinetic studiesTumor model systemsInter-patient variabilityStable diseaseII trialObjective responseAdverse eventsI trialAdvanced cancer
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