2016
A 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 criteria
2013
Phase 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 Bortezomib (PS-341; NSC 681239) and Alvocidib (Flavopiridol; NSC 649890) in Patients with Recurrent or Refractory Indolent B-Cell Neoplasms - Update of the “Bolus” Infusion Schedule of Alvocidib.
Holkova B, Perkins E, Bose P, Sullivan D, Baz R, Tombes M, Shrader E, Ramakrishnan V, Wan W, Sankala H, Kmieciak M, Roberts J, Grant S. Phase I Trial of Bortezomib (PS-341; NSC 681239) and Alvocidib (Flavopiridol; NSC 649890) in Patients with Recurrent or Refractory Indolent B-Cell Neoplasms - Update of the “Bolus” Infusion Schedule of Alvocidib. Blood 2012, 120: 2959. DOI: 10.1182/blood.v120.21.2959.2959.Peer-Reviewed Original ResearchAdverse eventsInfusion scheduleMultiple myelomaI trialDose levelsAbsolute neutrophil count decreaseGrade 2 adverse eventsCTCAE version 4Grade 5 eventsIndolent B-cell neoplasmsNeutrophil count decreasePrior systemic therapyPhase II studyECOG performance scoreRefractory multiple myelomaTreatment of recurrentTumor lysis syndromePhase I trialSchedule of administrationCombination of bortezomibIndolent B-cellExpression of pJNKB-cell neoplasmsNF-κB DNA bindingMcl-1
2008
Phase I Trial of Bortezomib (NSC 681239) and Flavopiridol (NSC 649890) in Patients with Recurrent or Refractory Indolent B-Cell Neoplasms.
Grant S, Sullivan D, Roodman D, Stuart R, Perkins E, Kolla S, Ramakrishnan V, Wright J, Colevas A, Tombes M, Roberts J. Phase I Trial of Bortezomib (NSC 681239) and Flavopiridol (NSC 649890) in Patients with Recurrent or Refractory Indolent B-Cell Neoplasms. Blood 2008, 112: 1573. DOI: 10.1182/blood.v112.11.1573.1573.Peer-Reviewed Original ResearchB-cell neoplasmsDose levelsBolus scheduleI trialMinor responseNF-kappaB nuclear localizationIndolent B-cell neoplasmsPhase II evaluationPhase I trialPhospho-JNKCorrelative laboratory studiesNF-kappaB DNA bindingChronic lymphocytic leukemiaB-cell malignanciesBone marrow CD138Mcl-1Evaluable patientsStable diseaseEligible patientsPostural hypotensionHerpes zosterPartial responseRefractory diseaseStandard therapySystemic therapyPhase I Trial of Vorinostat (SAHA) in Combination with Alvocidib (Flavopiridol) in Patients with Relapsed, Refractory or (Selected) Poor Prognosis Acute Leukemia or Refractory Anemia with Excess Blasts-2 (RAEB-2)
Grant S, Kolla S, Sirulnik L, Shapiro G, Supko J, Cooper B, Perkins E, Ramakrishnan V, Espinoza-Delgado I, Tombes M, Roberts J. Phase I Trial of Vorinostat (SAHA) in Combination with Alvocidib (Flavopiridol) in Patients with Relapsed, Refractory or (Selected) Poor Prognosis Acute Leukemia or Refractory Anemia with Excess Blasts-2 (RAEB-2). Blood 2008, 112: 2986. DOI: 10.1182/blood.v112.11.2986.2986.Peer-Reviewed Original ResearchAcute leukemiaDose levelsStandard therapyI trialDay 1Grade 4 non-hematologic toxicityPoor-prognosis acute leukemiaDe novo acute leukemiaExcess blasts-2High-risk AMLNon-hematologic toxicitiesRemission induction failurePoor risk factorsImatinib-Refractory Chronic Myeloid LeukemiaPhase I trialPhase II evaluationAML/MDSCorrelative laboratory studiesNovo acute leukemiaChronic myeloid leukemiaHDAC inhibitor vorinostatCDK inhibitor flavopiridolAbsence of leukemiaPost-treatment effectsBolus schedule
2005
Phase I Study of Flavopiridol in Combination with Imatinib Mesylate (STI571, Gleevec) in Bcr/Abl+ Hematological Malignancies.
Grant S, Karp J, Koc O, Cooper B, Luger S, Figg W, Egorin M, Druker B, Jacobberger J, Ramakrishnan V, Perkins E, Colevas A, Roberts J. Phase I Study of Flavopiridol in Combination with Imatinib Mesylate (STI571, Gleevec) in Bcr/Abl+ Hematological Malignancies. Blood 2005, 106: 1102. DOI: 10.1182/blood.v106.11.1102.1102.Peer-Reviewed Original ResearchComplete hematological remissionAcute lymphocytic leukemiaBCR/Dose levelsHematological remissionStratum 2Dose level 3Dose level 4Weekly x 3Phase II doseStratum 1Phase II trialDaily oral dosingLeukemia cellsPhase I trialRecent preclinical studiesLeukemic cell deathBCR/ABL kinasePost-treatment effectsEligible patientsBlast percentageCyclin-dependent kinase inhibitorFrequent toxicitiesII trialObjective responsePhase I Trial of Bortezomib (NSC 681239) and Flavopiridol (NSC 649890) in Patients with Recurrent or Refractory Indolent B-Cell Neoplasms.
Grant S, Sullivan D, Roodman D, Stuart R, Perkins E, Ramakrishnan V, Wright J, Colevas A, Roberts J. Phase I Trial of Bortezomib (NSC 681239) and Flavopiridol (NSC 649890) in Patients with Recurrent or Refractory Indolent B-Cell Neoplasms. Blood 2005, 106: 3338. DOI: 10.1182/blood.v106.11.3338.3338.Peer-Reviewed Original ResearchI trialDose levelsPre-existing peripheral neuropathyIndolent B-cell lymphomaNF-kappaB nuclear localizationIndolent B-cell neoplasmsCase of exacerbationPhase I trialPhase II evaluationPhospho-JNKCorrelative laboratory studiesNF-kappaB DNA bindingB-cell lymphomaB-cell malignanciesBone marrow CD138B-cell neoplasmsMcl-1Eligible patientsStable diseaseHerpes zosterPartial responseRefractory diseaseStandard therapySystemic therapyComplete response
2000
Phase I study of AG2034, a targeted GARFT inhibitor, administered once every 3 weeks
Roberts J, Shibata S, Spicer D, McLeod H, Tombes M, Kyle B, Carroll M, Sheedy B, Collier M, Pithavala Y, Paradiso L, Clendeninn N. Phase I study of AG2034, a targeted GARFT inhibitor, administered once every 3 weeks. Cancer Chemotherapy And Pharmacology 2000, 45: 423-427. PMID: 10803927, DOI: 10.1007/s002800051012.Peer-Reviewed Original ResearchConceptsDose-limiting toxicityPhase II doseCumulative toxicityAdvanced malignanciesIntravenous bolusAUC0-24Pharmacodynamic factorsFolate supplementationPlasma concentrationsIntermediate dosePharmacokinetic analysisDose levelsELISA assaysDosePhase IAG2034Progressive increaseGARFT inhibitorToxicityWeeksInhibitorsMucositisThrombocytopeniaDiarrheaHyperbilirubinemia
1991
A phase i clinical trial of didemnin B
Stewart J, Low J, Roberts J, Blow A. A phase i clinical trial of didemnin B. Cancer 1991, 68: 2550-2554. PMID: 1933801, DOI: 10.1002/1097-0142(19911215)68:12<2550::aid-cncr2820681203>3.0.co;2-q.Peer-Reviewed Original ResearchConceptsM2/dDrug-induced liver dysfunctionPhase I clinical trialPhase II doseHepatic enzyme levelsDose-limiting toxicityComplete tumor responseCastor oil vehicleMurine B16 melanomaDidemnin BBolus scheduleClinical bleedingLiver dysfunctionAdvanced cancerAnaphylactic symptomsTumor responseClinical trialsDrug infusionL1210 growthOil vehicleM5076 sarcomaB16 melanomaDose levelsSporadic elevationsToxicologic tests
1990
Phase I trial of intraperitoneal recombinant interleukin-2/lymphokine-activated killer cells in patients with ovarian cancer.
Stewart JA, Belinson JL, Moore AL, Dorighi JA, Grant BW, Haugh LD, Roberts JD, Albertini RJ, Branda RF. Phase I trial of intraperitoneal recombinant interleukin-2/lymphokine-activated killer cells in patients with ovarian cancer. Cancer Research 1990, 50: 6302-10. PMID: 2205379.Peer-Reviewed Original ResearchConceptsLymphokine-activated killer cellsRecombinant interleukin-2LAK activityIL-2Killer cellsDose levelsMononuclear cellsUnits/m2 body surface areaIntraperitoneal recombinant interleukin-2M2 body surface areaLAK/ILOvarian cancer refractorySerum IL-2Less IL-2Dose-limiting toxicityPhase I trialIL-2 levelsAdditional IL-2IL-2-dependent cell lineBody surface areaSignificant weight gainMononuclear cell collectionPeripheral blood cellsHighest dose levelCancer refractory
1988
Phase I clinical and pharmacokinetic study of trimetrexate using a daily x5 schedule.
Stewart JA, McCormack JJ, Tong W, Low JB, Roberts JD, Blow A, Whitfield LR, Haugh LD, Grove WR, Lopez AJ. Phase I clinical and pharmacokinetic study of trimetrexate using a daily x5 schedule. Cancer Research 1988, 48: 5029-35. PMID: 2970294.Peer-Reviewed Original ResearchConceptsWhite blood cellsM2/dGood performance status patientsMedian white blood cellPhase IDaily x5 schedulePhase II trialPharmacokinetic studyColon 26 tumorMurine i.Nonhematological toxicitiesPlatelet nadirsPrior therapyII trialStarting doseStatus patientsDose escalationTerminal eliminationDose administeredPlatelet toxicityDaily dosesSchedule dependencyPharmacokinetic analysisB16 melanomaDose levels