2020
Phase 1 study of belinostat (PXD-101) and bortezomib (Velcade, PS-341) in patients with relapsed or refractory acute leukemia and myelodysplastic syndrome
Holkova B, Shafer D, Yazbeck V, Dave S, Bose P, Tombes MB, Shrader E, Wan W, Bandyopadhyay D, Weir C, Collins EB, Garnett A, Kmieciak M, Roberts JD, Garcia-Manero G, Grant S. Phase 1 study of belinostat (PXD-101) and bortezomib (Velcade, PS-341) in patients with relapsed or refractory acute leukemia and myelodysplastic syndrome. Leukemia & Lymphoma 2020, 62: 1187-1194. PMID: 33356689, PMCID: PMC8106643, DOI: 10.1080/10428194.2020.1861270.Peer-Reviewed Original ResearchConceptsStable diseaseAcute leukemiaDay 1Phase 1 dose-escalation studyRefractory acute leukemiaDose-escalation studyPhase 1 studyWhole-exome sequencingComplete pathologicKaryotypic responseAdult patientsQTc prolongationFirst patientMyelodysplastic syndromeTreatment strategiesBlast crisisPatientsExceptional responseKaryotypic aberrationsBelinostatGood responseBortezomibAMLLeukemiaFurther investigation
2012
Phase I Trial of Belinostat and Bortezomib in Patients with Relapsed or Refractory Acute Leukemia, Myelodysplastic Syndrome, or Chronic Myelogenous Leukemia in Blast Crisis - One Year Update
Holkova B, Bose P, Tombes M, Shrader E, Wan W, Weir-Wiggins C, Stoddert E, Sankala H, Kmieciak M, Roberts J, Garcia-Manero G, Grant S. Phase I Trial of Belinostat and Bortezomib in Patients with Relapsed or Refractory Acute Leukemia, Myelodysplastic Syndrome, or Chronic Myelogenous Leukemia in Blast Crisis - One Year Update. Blood 2012, 120: 3588. DOI: 10.1182/blood.v120.21.3588.3588.Peer-Reviewed Original ResearchHematopoietic stem cell transplantationStem cell transplantationAcute myeloid leukemiaRefractory acute leukemiaDose level 5Myelodysplastic syndromeStable diseaseCycles of treatmentPartial responseComplete responseAcute leukemiaChronic myelogenous leukemiaCML-BCAdverse eventsI trialMyelogenous leukemiaDay 1Allogeneic hematopoietic stem cell transplantationIncomplete blood count recoveryTreatment-related adverse eventsPrimary acute myeloid leukemiaAcute leukemia refractoryBlood count recoveryDose level 4Second partial response
2011
Phase I Trial of Belinostat and Bortezomib in Patients with Relapsed or Refractory Acute Leukemia, Myelodysplastic Syndrome, or Chronic Myelogenous Leukemia in Blast Crisis
Holkova B, Tombes M, Shrader E, Cooke S, Wan W, Sankala H, Kmieciak M, Roberts J, Garcia-Manero G, Grant S. Phase I Trial of Belinostat and Bortezomib in Patients with Relapsed or Refractory Acute Leukemia, Myelodysplastic Syndrome, or Chronic Myelogenous Leukemia in Blast Crisis. Blood 2011, 118: 2598. DOI: 10.1182/blood.v118.21.2598.2598.Peer-Reviewed Original ResearchRefractory acute leukemiaMyelodysplastic syndromeAcute leukemiaChronic myelogenous leukemiaMyelogenous leukemiaI trialCML-BCBlast crisisDay 1ECOG performance score 0Hematopoietic stem cell transplantationPerformance score 0Phase II dosesRecent preclinical findingsPeripheral sensory neuropathySerious adverse eventsMinute intravenous infusionPhase I trialPhase II evaluationPrimary acute myelogenous leukemiaSchedule of administrationStem cell transplantationBiphenotypic acute leukemiaCombination of bortezomibAcute myelogenous leukemia
2002
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.
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