FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2317505970> ?p ?o ?g. }

• W2317505970 endingPage "631" @default.
• W2317505970 startingPage "622" @default.
• W2317505970 abstract "Treatment options for patients with relapsed or refractory lymphoma and multiple myeloma are limited. CUDC-907 is an oral, first-in-class, small molecule that is designed to inhibit both histone deacetylase (HDAC) and PI3K enzymes, which are members of common oncogenic pathways in haematological malignancies. We aimed to assess overall safety and preliminary activity in this dose-escalation study of CUDC-907 monotherapy in patients with relapsed or refractory lymphoma and multiple myeloma.This open-label, first-in-man, phase 1 trial recruited adult patients (aged ≥18 years) with lymphoma or multiple myeloma who were refractory to or had relapsed after two or more previous regimens, from four US cancer centres. CUDC-907 was orally administered in a standard 3 + 3 dose-escalation design at four different dosing schedules, to which participants were sequentially assigned as follows: once daily, intermittently (twice or three times weekly; simultaneous enrolment), and daily for 5 days followed by a 2-day break (5/2), in 21-day cycles. Dosing started at 30 mg for the once-daily schedule and 60 mg for other schedules, escalating in 30 mg increments. Patients continued to receive CUDC-907 until disease progression or until other treatment discontinuation criteria were met. The primary objective was to determine the maximum tolerated dose (MTD) and recommended phase 2 dose, assessed in patients who received at least 66% of cycle 1 doses without modification and those who had a dose-limiting toxicity (DLT) in cycle 1 irrespective of dose modification. We assessed safety in all patients who received at least one dose of study drug. This ongoing trial is registered at ClinicalTrials.gov, number NCT01742988.Between Jan 23, 2013, and July 27, 2015, we enrolled 44 patients, of whom ten were sequentially assigned to CUDC-907 once-daily (MTD 60 mg), 12 to twice-weekly (MTD 150 mg), 15 to three-times-weekly (MTD 150 mg), and seven to the 5/2 dosing schedule (MTD 60 mg). 37 (84%) patients had discontinued study drug as a result of progressive disease or clinical signs of progressive disease at the data cutoff. Four DLTs occurred in three of 40 DLT-evaluable patients (diarrhoea and hyperglycaemia in one patient on 60 mg once daily, hyperglycaemia in one patient on 150 mg twice weekly, and diarrhoea in one patient on 150 mg three times weekly); no DLTs were reported in patients on the 5/2 schedule. Grade 3 or worse adverse events occurred in 19 (43%) of 44 patients, the most common of which were thrombocytopenia (in nine [20%] of 44 patients), neutropenia (three [7%]), and hyperglycaemia (three [7%]). 11 (25%) of 44 patients had serious adverse events, three of which were regarded as treatment related (epistaxis and the DLTs of diarrhoea and hyperglycaemia). Adverse events led to dose reductions in six (14%) patients and treatment discontinuation in seven (16%). Five (14%) of 37 response-evaluable patients achieved an objective response (two complete responses and three partial responses). All five responses occurred in the subgroup of patients with diffuse large B-cell lymphoma (DLBCL; n=9), and three occurred in those with transformed follicular lymphoma DLBCL (n=5). 21 (57%) of 37 response-evaluable patients had stable disease, including those with DLBCL, Hodgkin's lymphoma, and multiple myeloma. On the basis of these findings, we selected CUDC-907 60 mg on the 5/2 dosing schedule as the recommended phase 2 dose.The safety and tolerability profile of CUDC-907 and the promising preliminary evidence of response support continued development of CUDC-907 at the 60 mg 5/2 dosing schedule, alone and in combination with other therapies. A dose-expansion trial of this dose in patients with refractory and relapsed DLBCL in particular, is ongoing.Curis, Inc, and the Leukemia and Lymphoma Society." @default.
• W2317505970 created "2016-06-24" @default.
• W2317505970 creator A5005555673 @default.
• W2317505970 creator A5005718112 @default.
• W2317505970 creator A5005922094 @default.
• W2317505970 creator A5011559739 @default.
• W2317505970 creator A5021657948 @default.
• W2317505970 creator A5030806657 @default.
• W2317505970 creator A5037677450 @default.
• W2317505970 creator A5037784199 @default.
• W2317505970 creator A5050961257 @default.
• W2317505970 creator A5054094192 @default.
• W2317505970 creator A5064752432 @default.
• W2317505970 creator A5065054247 @default.
• W2317505970 creator A5068152076 @default.
• W2317505970 creator A5069721801 @default.
• W2317505970 creator A5080636708 @default.
• W2317505970 date "2016-05-01" @default.
• W2317505970 modified "2023-10-10" @default.
• W2317505970 title "Safety, tolerability, and preliminary activity of CUDC-907, a first-in-class, oral, dual inhibitor of HDAC and PI3K, in patients with relapsed or refractory lymphoma or multiple myeloma: an open-label, dose-escalation, phase 1 trial" @default.
• W2317505970 cites W2002106466 @default.
• W2317505970 cites W2014941193 @default.
• W2317505970 cites W2033218397 @default.
• W2317505970 cites W2044436186 @default.
• W2317505970 cites W2056641238 @default.
• W2317505970 cites W2062843952 @default.
• W2317505970 cites W2071361048 @default.
• W2317505970 cites W2107661677 @default.
• W2317505970 cites W2115593774 @default.
• W2317505970 cites W2133201432 @default.
• W2317505970 cites W2141920998 @default.
• W2317505970 cites W2143204311 @default.
• W2317505970 cites W2150099906 @default.
• W2317505970 cites W2150587745 @default.
• W2317505970 cites W2156928849 @default.
• W2317505970 cites W2172003817 @default.
• W2317505970 cites W2266142448 @default.
• W2317505970 cites W2553899159 @default.
• W2317505970 cites W2557113503 @default.
• W2317505970 cites W2562959513 @default.
• W2317505970 cites W2601229823 @default.
• W2317505970 cites W2601555696 @default.
• W2317505970 cites W2979839758 @default.
• W2317505970 cites W2332179735 @default.
• W2317505970 doi "https://doi.org/10.1016/s1470-2045(15)00584-7" @default.
• W2317505970 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5494693" @default.
• W2317505970 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/27049457" @default.
• W2317505970 hasPublicationYear "2016" @default.
• W2317505970 type Work @default.
• W2317505970 sameAs 2317505970 @default.
• W2317505970 citedByCount "137" @default.
• W2317505970 countsByYear W23175059702016 @default.
• W2317505970 countsByYear W23175059702017 @default.
• W2317505970 countsByYear W23175059702018 @default.
• W2317505970 countsByYear W23175059702019 @default.
• W2317505970 countsByYear W23175059702020 @default.
• W2317505970 countsByYear W23175059702021 @default.
• W2317505970 countsByYear W23175059702022 @default.
• W2317505970 countsByYear W23175059702023 @default.
• W2317505970 crossrefType "journal-article" @default.
• W2317505970 hasAuthorship W2317505970A5005555673 @default.
• W2317505970 hasAuthorship W2317505970A5005718112 @default.
• W2317505970 hasAuthorship W2317505970A5005922094 @default.
• W2317505970 hasAuthorship W2317505970A5011559739 @default.
• W2317505970 hasAuthorship W2317505970A5021657948 @default.
• W2317505970 hasAuthorship W2317505970A5030806657 @default.
• W2317505970 hasAuthorship W2317505970A5037677450 @default.
• W2317505970 hasAuthorship W2317505970A5037784199 @default.
• W2317505970 hasAuthorship W2317505970A5050961257 @default.
• W2317505970 hasAuthorship W2317505970A5054094192 @default.
• W2317505970 hasAuthorship W2317505970A5064752432 @default.
• W2317505970 hasAuthorship W2317505970A5065054247 @default.
• W2317505970 hasAuthorship W2317505970A5068152076 @default.
• W2317505970 hasAuthorship W2317505970A5069721801 @default.
• W2317505970 hasAuthorship W2317505970A5080636708 @default.
• W2317505970 hasBestOaLocation W23175059702 @default.
• W2317505970 hasConcept C121332964 @default.
• W2317505970 hasConcept C126322002 @default.
• W2317505970 hasConcept C142424586 @default.
• W2317505970 hasConcept C143998085 @default.
• W2317505970 hasConcept C197934379 @default.
• W2317505970 hasConcept C2776063141 @default.
• W2317505970 hasConcept C2776364478 @default.
• W2317505970 hasConcept C2777288759 @default.
• W2317505970 hasConcept C2778375690 @default.
• W2317505970 hasConcept C2778715236 @default.
• W2317505970 hasConcept C2779338263 @default.
• W2317505970 hasConcept C71924100 @default.
• W2317505970 hasConcept C87355193 @default.
• W2317505970 hasConcept C98274493 @default.
• W2317505970 hasConceptScore W2317505970C121332964 @default.
• W2317505970 hasConceptScore W2317505970C126322002 @default.
• W2317505970 hasConceptScore W2317505970C142424586 @default.
• W2317505970 hasConceptScore W2317505970C143998085 @default.
• W2317505970 hasConceptScore W2317505970C197934379 @default.
• W2317505970 hasConceptScore W2317505970C2776063141 @default.
• W2317505970 hasConceptScore W2317505970C2776364478 @default.
• W2317505970 hasConceptScore W2317505970C2777288759 @default.

• next