2009
Phase I study of bryostatin 1, a protein kinase C modulator, preceding cisplatin in patients with refractory non-hematologic tumors
Pavlick AC, Wu J, Roberts J, Rosenthal MA, Hamilton A, Wadler S, Farrell K, Carr M, Fry D, Murgo AJ, Oratz R, Hochster H, Liebes L, Muggia F. Phase I study of bryostatin 1, a protein kinase C modulator, preceding cisplatin in patients with refractory non-hematologic tumors. Cancer Chemotherapy And Pharmacology 2009, 64: 803. PMID: 19221754, PMCID: PMC3901370, DOI: 10.1007/s00280-009-0931-y.Peer-Reviewed Original ResearchConceptsPeripheral blood mononuclear cellsPhase INon-hematologic tumorsPhase II dosesPhase II doseDose-limiting toxicityResultsFifty-three patientsBlood mononuclear cellsNon-hematologic malignanciesBryostatin 1Cytotoxicity of cisplatinCisplatin 50PurposePreclinical dataObjective responseContinuous infusionMononuclear cellsTolerable dosesProtein kinase C modulatorsCisplatin effectComputerized tomographyPatientsConsistent inhibitionCisplatin cytotoxicityCisplatinMinimal toxicity
2006
Phase I Study of Bryostatin 1 and Fludarabine in Patients with Chronic Lymphocytic Leukemia and Indolent (Non-Hodgkin's) Lymphoma
Roberts JD, Smith MR, Feldman EJ, Cragg L, Millenson MM, Roboz GJ, Honeycutt C, Thune R, Padavic-Shaller K, Carter WH, Ramakrishnan V, Murgo AJ, Grant S. Phase I Study of Bryostatin 1 and Fludarabine in Patients with Chronic Lymphocytic Leukemia and Indolent (Non-Hodgkin's) Lymphoma. Clinical Cancer Research 2006, 12: 5809-5816. PMID: 17020988, DOI: 10.1158/1078-0432.ccr-05-2730.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsBryostatinsDose-Response Relationship, DrugDrug Administration ScheduleFemaleHumansLeukemia, Lymphocytic, Chronic, B-CellLymphoma, Non-HodgkinMacrolidesMaleMaximum Tolerated DoseMiddle AgedPrognosisSurvival RateVidarabineConceptsChronic lymphocytic leukemiaIndolent lymphomaLymphocytic leukemiaBryostatin 1Dose-limiting toxic eventsTreatment of CLLMonoclonal antibodiesPhase II dosePhase II dosesPhase II studyCD20 monoclonal antibodyII studyPersistent diseaseSuccessive patientsSingle doseContinuous infusionI studiesHematologic malignanciesPreclinical studiesTherapeutic effectFludarabinePatientsPrior treatmentLymphomaPhase I
2002
Phase I Study of Bryostatin-1 and Fludarabine in Patients with Chronic Lymphocytic Leukemia and Indolent Non-Hodgkin's Lymphoma
Roberts JD, Smith MR, Feldman EJ, Cragg L, Grant S. Phase I Study of Bryostatin-1 and Fludarabine in Patients with Chronic Lymphocytic Leukemia and Indolent Non-Hodgkin's Lymphoma. Clinical Lymphoma Myeloma & Leukemia 2002, 3: 184-188. PMID: 12521398, DOI: 10.3816/clm.2002.n.025.Peer-Reviewed Original ResearchPhase I trial and correlative laboratory studies of bryostatin 1 (NSC 339555) and high-dose 1-B-D-arabinofuranosylcytosine in patients with refractory acute leukemia.
Cragg LH, Andreeff M, Feldman E, Roberts J, Murgo A, Winning M, Tombes MB, Roboz G, Kramer L, Grant S. Phase I trial and correlative laboratory studies of bryostatin 1 (NSC 339555) and high-dose 1-B-D-arabinofuranosylcytosine in patients with refractory acute leukemia. Clinical Cancer Research 2002, 8: 2123-33. PMID: 12114412.Peer-Reviewed Original ResearchConceptsDose-limiting toxicityPhase I trialComplete remissionCorrelative laboratory studiesI trialAcute leukemiaSplit courseContinuous infusionVivo administrationBryostatin 1Ara-C dose levelsAutologous bone marrow transplantationMajor dose-limiting toxicityEx vivoRefractory acute leukemiaUnfavorable prognostic characteristicsHigh-risk featuresLeukemia-free survivalBone marrow transplantationCourse of therapyPKC activityTransfusion requirementsRefractory leukemiaRefractory/Latter patients
2001
Adoptive immunotherapy of cancer with pharmacologically activated lymph node lymphocytes: a pilot clinical trial
Bear H, Roberts J, Cornell D, Tombes M, Kyle B. Adoptive immunotherapy of cancer with pharmacologically activated lymph node lymphocytes: a pilot clinical trial. Cancer Immunology, Immunotherapy 2001, 50: 269-274. PMID: 11499810, PMCID: PMC11036846, DOI: 10.1007/s002620100199.Peer-Reviewed Original ResearchConceptsIL-2 infusionAdoptive immunotherapyClinical trialsInterleukin-2Low-dose interleukin-2Tumor-sensitized T cellsPhase I clinical trialLymph node cellsPilot clinical trialLymph node lymphocytesTarget cell numberCell numberNode lymphocytesNode cellsTumor regressionT cellsT lymphocytesUnexpected toxicitiesMurine modelAdditional trialsInfusionPhase ITrialsTechnical modificationsPatient cells
1998
Phase Ib trial of bryostatin 1 in patients with refractory malignancies.
Grant S, Roberts J, Poplin E, Tombes MB, Kyle B, Welch D, Carr M, Bear HD. Phase Ib trial of bryostatin 1 in patients with refractory malignancies. Clinical Cancer Research 1998, 4: 611-8. PMID: 9533528.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic AgentsBryostatinsCohort StudiesCytotoxicity, ImmunologicDrug Administration ScheduleFemaleHumansImmunophenotypingInfusions, IntravenousInterleukin-2LactonesLymphocyte ActivationLymphocytesLymphomaMacrolidesMaleMetabolic Clearance RateMiddle AgedNeoplasmsPatient SelectionPlatelet AggregationProtein Kinase CConceptsPhase Ib trialIb trialCohort 3Lymphokine-activated killer cell activityBryostatin 1Bryostatin-1 administrationObjective clinical responsesKiller cell activityLiver function testsSubset of patientsBryostatin 1 treatmentSignificant posttreatment increasePKC activitySplit courseClinical responseFirst doseLiver metastasesNonhematological malignanciesRefractory malignanciesFunction testsPatient cohortCohort 1Interleukin-2Immunophenotypic profileTransient elevation
1996
Bryostatin 1 activates splenic lymphocytes and induces sustained depletion of splenocyte protein kinase C activity in vivo after a single intravenous administration
Bear H, McFadden A, Kostuchenko P, Lipshy K, Hamad G, Turner A, Roberts J, Carr M, Carr S, Grant S. Bryostatin 1 activates splenic lymphocytes and induces sustained depletion of splenocyte protein kinase C activity in vivo after a single intravenous administration. Anti-Cancer Drugs 1996, 7: 299-306. PMID: 8792004, DOI: 10.1097/00001813-199605000-00010.Peer-Reviewed Original ResearchConceptsBryostatin 1Normal murine spleen cellsT-cell activation marker CD69PKC activityActivation marker CD69Single bolus injectionEarly lymphocyte activationSingle intravenous administrationAnti-tumor effectsNormal host tissuesCell surface phenotypeProtein kinase CMurine spleen cellsPlasma levels resultsRegulate protein kinase CAnti-cancer agentsControl miceMarked splenomegalyBolus injectionIntravenous administrationC57BI/6 miceSpleen cellsSplenocyte proliferationSplenic lymphocytesSurface phenotype