2023
Trial in Progress: An Open-Label Expansion Trial Evaluating the Safety, PK/PD, and Clinical Activity of Emavusertib (CA-4948) + Ibrutinib in R/R Primary CNS Lymphoma
Grommes C, Nowakowski G, Rosenthal A, Lunning M, Ramchandren R, Regales L, Fowle M, Lane M, Wang C, Omuro A, Leslie L, Soussain C, Dabrowska-Iwanicka A, Ferreri A, Tun H. Trial in Progress: An Open-Label Expansion Trial Evaluating the Safety, PK/PD, and Clinical Activity of Emavusertib (CA-4948) + Ibrutinib in R/R Primary CNS Lymphoma. Blood 2023, 142: 3143. DOI: 10.1182/blood-2023-190391.Peer-Reviewed Original ResearchPrimary central nervous system lymphomaInterleukin-1 receptor-associated kinase 4FMS-like tyrosine kinase 3Toll-like receptorsExpansion cohortPCNSL patientsDisease progressionRefractory primary central nervous system lymphomaDiagnosis of PCNSLCentral nervous system lymphomaPathogenesis of PCNSLSafety/tolerabilityOpen-label trialBlood-brain barrier penetrationPrimary CNS lymphomaSufficient blood-brain barrier penetrationNervous system lymphomaInitial clinical dataKey inclusion criteriaPotent oral inhibitorCentral nervous systemBrain barrier penetrationPK/PDTyrosine kinase 3Further preclinical studies
2018
Phase 1 study of pomalidomide and dexamethasone for relapsed/refractory primary CNS or vitreoretinal lymphoma
Tun HW, Johnston PB, DeAngelis LM, Atherton PJ, Pederson LD, Koenig PA, Reeder CB, Omuro AMP, Schiff D, O'Neill B, Pulido J, Jaeckle KA, Grommes C, Witzig TE. Phase 1 study of pomalidomide and dexamethasone for relapsed/refractory primary CNS or vitreoretinal lymphoma. Blood 2018, 132: 2240-2248. PMID: 30262659, PMCID: PMC6265643, DOI: 10.1182/blood-2018-02-835496.Peer-Reviewed Original ResearchConceptsPrimary central nervous system lymphomaOverall response ratePrimary vitreoretinal lymphomaProgression-free survivalRefractory primary central nervous system lymphomaComplete responsePartial responseVitreoretinal lymphomaGrade 3/4 hematologic toxicitiesGrade 3/4 nonhematologic toxicitiesMedian progression-free survivalCentral nervous system lymphomaDose escalation schedulePhase 1 studyNervous system lymphomaCombination of pomalidomideSignificant therapeutic activityMTD cohortNonhematologic toxicityHematologic toxicityRespiratory failureSystem lymphomaMTD determinationPrimary CNSSafety profile
2017
Phase I clinical trial on pomalidomide and dexamethasone in treating patients with relapsed/refractory primary central nervous system lymphoma (PCNSL) or primary vitreoretinal lymphoma (PVRL).
Tun H, Johnston P, Grommes C, Reeder C, Omuro A, Menke D, Copland J, DeAngelis L, Witzig T. Phase I clinical trial on pomalidomide and dexamethasone in treating patients with relapsed/refractory primary central nervous system lymphoma (PCNSL) or primary vitreoretinal lymphoma (PVRL). Journal Of Clinical Oncology 2017, 35: 7516-7516. DOI: 10.1200/jco.2017.35.15_suppl.7516.Peer-Reviewed Original ResearchPrimary central nervous system lymphomaOverall response rateRefractory primary central nervous system lymphomaPhase I clinical trialPrimary vitreoretinal lymphomaMTD cohortStable diseaseClinical trialsCentral nervous system lymphomaTherapeutic activityDiffuse large B-cell lymphomaLarge B-cell lymphomaDose level 3Grade 3/4 toxicitiesNovel immunomodulatory agentsNervous system lymphomaCycles of treatmentDose escalation levelsCSF/blood ratioB-cell lymphomaExcellent CNS penetrationPO weeklyPomalidomide treatmentPseudo progressionCNS lymphoma