0000000000164163

AUTHOR

Thomas J. Kipps

showing 6 related works from this author

Associations of ofatumumab exposure and treatment outcomes in patients with untreated CLL receiving chemoimmunotherapy

2016

Relationships between patient characteristics, ofatumumab pharmacokinetics, and treatment outcomes were investigated in this phase 2 trial of ofatumumab plus fludarabine and cyclophosphamide (FC) in untreated chronic lymphocytic leukemia. Patients were randomized 1:1 to receive 500 or 1000 mg ofatumumab (Cycle 1; 300 mg) plus FC every 4 weeks for six cycles. Median C(max) and C(trough) values were similar at Cycle 1 regardless of the ultimate clinical outcome. At later doses, these values were higher for patients with complete response (CR) than for other patients. Higher C(max) and C(trough) values at Cycles 3 and 6 were significantly associated with an increased likelihood of CR, whereas …

OncologyMaleCancer ResearchLymphomaDrug ResistanceMedizinKaplan-Meier EstimatePharmacologychemistry.chemical_compound0302 clinical medicineAntineoplastic Agents ImmunologicalRecurrencehemic and lymphatic diseasesAntineoplastic Combined Chemotherapy Protocols80 and overChronicNeoplasm MetastasisLenalidomideCancerAged 80 and overUnivariate analysisLeukemiaRemission InductionAntibodies MonoclonalHematologyphase IIMiddle AgedLymphocyticThalidomideFludarabineClinical trialTreatment OutcomeOncologyTolerability6.1 Pharmaceuticals030220 oncology & carcinogenesisRetreatmentMathematikRituximabFemalePatient SafetyRefractory Chronic Lymphocytic LeukemiaUntreated Chronic Lymphocytic Leukemiamedicine.drugAdultmedicine.medical_specialtyCyclophosphamidelenalidomideClinical Trials and Supportive ActivitiesClinical SciencesImmunologyCmaxAntineoplastic AgentsNeutropeniaOfatumumabAntibodies Monoclonal HumanizedDrug Administration ScheduleArticle03 medical and health sciencesRare DiseasesClinical ResearchChemoimmunotherapyInternal medicinemedicineImmunologic FactorsAnimalsHumansIn patientAdverse effectLenalidomideAgedNeoplasm StagingChromosome Aberrationsbusiness.industryB-CellEvaluation of treatments and therapeutic interventionsmedicine.diseaseHaresLeukemia Lymphocytic Chronic B-CellDiscontinuationClinical trialchemistryDrug Resistance NeoplasmNeoplasmbusinessCLL030215 immunology
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Ofatumumab Combined With Fludarabine and Cyclophosphamide (O-FC) Shows High Activity in Patients With Previously Untreated Chronic Lymphocytic Leukem…

2010

Abstract 207 Introduction: Chemoimmunotherapy regimens have become the treatment standard for patients with CLL. Ofatumumab is a human monoclonal antibody that targets a unique small-loop epitope on CD20 and elicits rapid and efficient in vitro complement-dependent cytotoxicity, as well as antibody-dependent cellular cytotoxicity. Recent studies demonstrated single-agent ofatumumab activity, with high overall response rates (ORR) in patients with refractory CLL. We conducted an international, randomized, parallel group, Phase II trial with two doses of ofatumumab combined with fludarabine and cyclophosphamide (FC) in previously untreated patients with CLL to evaluate the efficacy and tolera…

Cancer Researchmedicine.medical_specialtybusiness.industryMedizinHematologyNeutropeniamedicine.diseaseOfatumumabFludarabineRegimenchemistry.chemical_compoundOncologyTolerabilitychemistryChemoimmunotherapyInternal medicineImmunologymedicineRituximabbusinessFebrile neutropeniamedicine.drugClinical Lymphoma Myeloma and Leukemia
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Correlations Between Ofatumumab Exposure and Treatment Outcomes for patients with Chronic Lymphocytic Leukemia (CLL) Treated with Frontline Ofatumuma…

2011

Abstract Abstract 1793 Introduction: Results: Seven pts (4 male) with a medianLittle is known about the pharmacokinetics (PK) and pharmacodynamics of CD20 monoclonal antibody (mAb) with chemotherapy in patients (pts) with CLL. Ofatumumab (O) is a human mAb targeting a membrane-proximal small-loop epitope on CD20 and mediates efficient complement-dependent cytotoxicity and antibody-dependent cell-mediated cytotoxicity. Safety and efficacy of O at 2 dose levels in combination with fludarabine and cyclophosphamide (FC) were evaluated in previously untreated pts with CLL. Relationship between O PK, baseline characteristics, and clinical outcomes were studied. Pts and Methods: Pts with active CL…

Oncologymedicine.medical_specialtyCyclophosphamidebusiness.industryImmunologyCmaxCell BiologyHematologymedicine.diseaseOfatumumabBiochemistryFludarabinechemistry.chemical_compoundCminchemistryChemoimmunotherapyPharmacodynamicsInternal medicineImmunologymedicinebusinessProgressive diseasemedicine.drug
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The down-regulation of miR-125b in chronic lymphocytic leukemias leads to metabolic adaptation of cells to a transformed state

2012

AbstractMiR-125b-1 maps at 11q24, a chromosomal region close to the epicenter of 11q23 deletions in chronic lymphocytic leukemias (CLLs). Our results establish that both aggressive and indolent CLL patients show reduced expression of miR-125b. Overexpression of miR-125b in CLL-derived cell lines resulted in the repression of many transcripts encoding enzymes implicated in cell metabolism. Metabolomics analyses showed that miR-125b overexpression modulated glucose, glutathione, lipid, and glycerolipid metabolism. Changes on the same metabolic pathways also were observed in CLLs. We furthermore analyzed the expression of some of miR-125b–target transcripts that are potentially involved in the…

Blotting WesternImmunologyBiologyReal-Time Polymerase Chain ReactionBiochemistryNODownregulation and upregulationmicroRNABiomarkers TumorHumansMetabolomicsRNA MessengerPsychological repressionCells CulturedCell ProliferationOligonucleotide Array Sequence AnalysisRegulation of gene expressionB-LymphocytesLymphoid NeoplasiaReverse Transcriptase Polymerase Chain ReactionCell growthGene Expression ProfilingCell BiologyHematologyLeukemia Lymphocytic Chronic B-CellMolecular biologyGene Expression Regulation NeoplasticGene expression profilingMicroRNAsMetabolic pathwayCell Transformation NeoplasticChromosomal regionCancer researchBlood
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Quaking and miR-155 interactions in inflammation and leukemogenesis.

2015

Quaking (QKI) is a tumor-suppressor gene encoding a conserved RNA-binding protein, whose expression is downregulated in several solid tumors. Here we report that QKI plays an important role in the immune response and suppression of leukemogenesis. We show that the expression of Qki is reduced in lipopolysaccharide (LPS)-challenged macrophages, suggesting that Qki is a key regulator of LPS signaling pathway. Furthermore, LPS-induced downregulation of Qki expression is miR-155-dependent. Qki overexpression impairs LPS-induced phosphorylation of JNK and particularly p38 MAPKs, in addition to increasing the production of anti-inflammatory cytokine IL-10. In contrast, Qki ablation decreases Fas …

LipopolysaccharidesTime Factorsmedicine.medical_treatmentmedicine.disease_causeTransgenicMiceInnatePhosphorylationChronicB-LymphocytesLeukemiaRNA-Binding ProteinsU937 CellsLymphocyticCell biologyCytokineOncologyPhosphorylationCytokinesCLL; Glioblastoma; Inflammation; MiR-155; QKI; Animals; Apoptosis Regulatory Proteins; B-Lymphocytes; Case-Control Studies; Cytokines; Humans; Immunity Innate; Inflammation; Leukemia Lymphocytic Chronic B-Cell; Lipopolysaccharides; Macrophages; Mice; Mice Transgenic; MicroRNAs; Mitogen-Activated Protein Kinases; Phosphorylation; RAW 264.7 Cells; RNA-Binding Proteins; Signal Transduction; Time Factors; Transfection; U937 Cells; OncologySignal transductionMitogen-Activated Protein KinasesSignal Transductionp38 mitogen-activated protein kinasesOncology and CarcinogenesisMice TransgenicTransfectionNOmiR-155miR-155Downregulation and upregulationmicroRNAmedicineAnimalsHumansInflammationQKIbusiness.industryMacrophagesB-CellImmunityglioblastomaLeukemia Lymphocytic Chronic B-CellImmunity InnateMicroRNAsRAW 264.7 CellsCase-Control StudiesImmunologyCarcinogenesisbusinessApoptosis Regulatory ProteinsCLLPriority Research Paper
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Chemoimmunotherapy with O-FC in previously untreated patients with chronic lymphocytic leukemia

2011

We conducted an international phase 2 trial to evaluate 2 dose levels of ofatumumab, a human CD20 mAb, combined with fludarabine and cyclophosphamide (O-FC) as frontline therapy for chronic lymphocytic leukemia (CLL). Patients with active CLL were randomized to ofatumumab 500 mg (n = 31) or 1000 mg (n = 30) day 1, with fludarabine 25 mg/m2 and cyclophosphamide 250 mg/m2 days 2-4, course 1; days 1-3, courses 2-6; every 4 weeks for 6 courses. The first ofatumumab dose was 300 mg for both cohorts. The median age was 56 years; 13% of patients had a 17p deletion; 64% had β2-microglobulin > 3.5 mg/L. Based on the 1996 National Cancer Institute Working Group (NCI-WG) guidelines, the complete respo…

Malemedicine.medical_specialtyCyclophosphamideClinical Trials and ObservationsChronic lymphocytic leukemiaImmunologyMedizinNeutropeniaOfatumumabAntibodies Monoclonal HumanizedBiochemistryGastroenterologychemistry.chemical_compoundChemoimmunotherapyInternal medicineAntineoplastic Combined Chemotherapy ProtocolsmedicineHumansCyclophosphamideCD20Chlorambucilbiologybusiness.industryAntibodies MonoclonalCell BiologyHematologyMiddle Agedmedicine.diseaseCombined Modality TherapyLeukemia Lymphocytic Chronic B-CellNeoadjuvant TherapySurgeryFludarabineTreatment Outcomechemistrybiology.proteinFemaleImmunotherapybusinessVidarabinemedicine.drug
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