FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2910368428> ?p ?o ?g. }

• W2910368428 endingPage "893" @default.
• W2910368428 startingPage "893" @default.
• W2910368428 abstract "Abstract Introduction: First line therapy of AML has not changed significantly since the 1970s and still relies on cytarabine as its backbone. Older patients or patients with comorbidities have low tolerability to intensive cytarabine treatment due to increased morbidity and mortality related to its toxicity, such as cerebellar toxicity, bone marrow suppression, gastrointestinal toxicity and infections. Hence, currently available intensive cytarabine treatment is unjustified in this population due to its poor risk/benefit ratio, and therefore, older and unfit AML patients are usually treated with reduced intensity therapy with poor outcomes. BST-236 is a new compound of cytarabine covalently bound to asparagine. It acts as a pro-drug of cytarabine, enabling delivery of high cytarabine doses to leukemia cells with lower systemic exposure to the free drug and relative sparing of normal tissues. As such, BST-236 may serve as an ideal therapy for leukemia, particularly for delivering high doses of cytarabine to medically unfit or older adults. The aim of this Phase I/II study was to evaluate the safety and optimal dose of BST-236 in refractory/relapsed or newly-diagnosed acute leukemia patients unfit for standard induction therapy. Methods: Acute leukemia patients, either relapsed/refractory, or older or unfit newly-diagnosed, were enrolled to a prospective open label single arm study. The study included 6 dose-escalating cohorts of patients treated with 6 daily doses of BST-236 administered as a 1-hour intravenous infusion. Cohorts 1-4 enrolled patients age ≥18 years, dosed with 0.5 g/m2, 1.5 g/m2, 3 g/m2 or 4.5 g/m2, respectively, with a 50% dose reduction in each cohort for patients age &gt;50 years. Cohorts 5 and 6 enrolled patients ≥70 years of age, dosed with 4.5 g/m2 or 6 g/m2, respectively (Table 1). Results: Twenty-six (26) patients received at least 2 daily doses of BST-236, twenty-three (23) of them (14 males and 9 females) completed at least one 6-day treatment course, including 2 patients who received 2 courses. Out of the 23 patients who completed at least one treatment course, median age 77 (range 27-90), 6 had relapsed/refractory AML following standard chemotherapy, median age 64 years (range 27-81), 15 were newly-diagnosed AML patients unfit for standard chemotherapy, median age 78 years (range 70-89), including 11 patients (73%) with AML secondary to myelodysplastic disorder (MDS) or myeloproliferative neoplasms, median age 77 years (range 70-89), and 2 patients with de novo ALL, age 79 and 90. BST-236 treatment was well-tolerated and MTD was not reached in this study. Notably, the maximal dose of 6 g/m2/d BST-236 is the molar equivalent of 4 g/m2/d of cytarabine. Moreover, adverse events were mainly hematological on-target events, and no neurological events or &gt;grade 2 events such as mucositis, diarrhea, or alopecia were reported in any of the cohorts during treatment or within 30 days of follow up. Assessment of the outcome of cohort 6 is still ongoing and will be available in the coming weeks. The majority of the newly diagnosed AML patients in cohorts 1-5 responded to BST-236 (Figure 1). The overall response and Complete Remission (CR) rates, of the newly-diagnosed AML patients (de novo and secondary to MDS) was 71% and 43%, respectively. Follow up of the Overall Survival (OS) of these patients is still ongoing, and is currently 6.9 months (active) for all responders, 9.2 months (active) for CR patients, and 0.6 months for the non-responders (Figure 2). Notably, 67% of the responding patients had secondary AML, refractory to hypomethylating agents (HMA). No CR was reached in the 6 patients suffering from relapse or refractory AML, and their median OS was 2.3 months (Figure 2). Conclusions: This Phase I/II study demonstrates that BST-236, a cytarabine pro-drug, is able to safely deliver high-dose cytarabine to older and unfit patients (median age 78) with no significant typical cytarabine toxicities other than on-target hematological events. Moreover, the general wellbeing of the patients during and after administration, as noted by the treating physicians, was exceptionally improved compared to intensive therapy. The good safety profile, accompanied by the high response rates and significantly prolonged survival of the older and unfit newly-diagnosed population, most of them refractory to HMA, is highly encouraging. A phase II study is planned to confirm these results. Disclosures Zuckerman: BioSight Ltd.: Consultancy. Gengrinovitch: Biosight: Employment. Flaishon: BioSight: Employment. Ben Yakar: Biosight: Employment." @default.
• W2910368428 created "2019-01-25" @default.
• W2910368428 creator A5005482633 @default.
• W2910368428 creator A5011180142 @default.
• W2910368428 creator A5012003196 @default.
• W2910368428 creator A5019745896 @default.
• W2910368428 creator A5027722797 @default.
• W2910368428 creator A5040016022 @default.
• W2910368428 creator A5042528560 @default.
• W2910368428 creator A5044035119 @default.
• W2910368428 creator A5053047062 @default.
• W2910368428 creator A5053411706 @default.
• W2910368428 creator A5060645770 @default.
• W2910368428 creator A5065418651 @default.
• W2910368428 creator A5068847117 @default.
• W2910368428 creator A5082530021 @default.
• W2910368428 creator A5087250069 @default.
• W2910368428 date "2017-12-07" @default.
• W2910368428 modified "2023-10-14" @default.
• W2910368428 title "BST-236, a Novel Cytarabine Pro-Drug, Enables Safe and Effective Administration of High Dose Cytarabine to Older or Unfit Patients with Acute Leukemia. Results of a Phase I/II Study" @default.
• W2910368428 doi "https://doi.org/10.1182/blood.v130.suppl_1.893.893" @default.
• W2910368428 hasPublicationYear "2017" @default.
• W2910368428 type Work @default.
• W2910368428 sameAs 2910368428 @default.
• W2910368428 citedByCount "1" @default.
• W2910368428 countsByYear W29103684282019 @default.
• W2910368428 crossrefType "journal-article" @default.
• W2910368428 hasAuthorship W2910368428A5005482633 @default.
• W2910368428 hasAuthorship W2910368428A5011180142 @default.
• W2910368428 hasAuthorship W2910368428A5012003196 @default.
• W2910368428 hasAuthorship W2910368428A5019745896 @default.
• W2910368428 hasAuthorship W2910368428A5027722797 @default.
• W2910368428 hasAuthorship W2910368428A5040016022 @default.
• W2910368428 hasAuthorship W2910368428A5042528560 @default.
• W2910368428 hasAuthorship W2910368428A5044035119 @default.
• W2910368428 hasAuthorship W2910368428A5053047062 @default.
• W2910368428 hasAuthorship W2910368428A5053411706 @default.
• W2910368428 hasAuthorship W2910368428A5060645770 @default.
• W2910368428 hasAuthorship W2910368428A5065418651 @default.
• W2910368428 hasAuthorship W2910368428A5068847117 @default.
• W2910368428 hasAuthorship W2910368428A5082530021 @default.
• W2910368428 hasAuthorship W2910368428A5087250069 @default.
• W2910368428 hasBestOaLocation W29103684281 @default.
• W2910368428 hasConcept C121332964 @default.
• W2910368428 hasConcept C126322002 @default.
• W2910368428 hasConcept C141071460 @default.
• W2910368428 hasConcept C142424586 @default.
• W2910368428 hasConcept C197934379 @default.
• W2910368428 hasConcept C2776863199 @default.
• W2910368428 hasConcept C2778041864 @default.
• W2910368428 hasConcept C2778375690 @default.
• W2910368428 hasConcept C2778461978 @default.
• W2910368428 hasConcept C2908647359 @default.
• W2910368428 hasConcept C71924100 @default.
• W2910368428 hasConcept C87355193 @default.
• W2910368428 hasConcept C90924648 @default.
• W2910368428 hasConcept C99454951 @default.
• W2910368428 hasConceptScore W2910368428C121332964 @default.
• W2910368428 hasConceptScore W2910368428C126322002 @default.
• W2910368428 hasConceptScore W2910368428C141071460 @default.
• W2910368428 hasConceptScore W2910368428C142424586 @default.
• W2910368428 hasConceptScore W2910368428C197934379 @default.
• W2910368428 hasConceptScore W2910368428C2776863199 @default.
• W2910368428 hasConceptScore W2910368428C2778041864 @default.
• W2910368428 hasConceptScore W2910368428C2778375690 @default.
• W2910368428 hasConceptScore W2910368428C2778461978 @default.
• W2910368428 hasConceptScore W2910368428C2908647359 @default.
• W2910368428 hasConceptScore W2910368428C71924100 @default.
• W2910368428 hasConceptScore W2910368428C87355193 @default.
• W2910368428 hasConceptScore W2910368428C90924648 @default.
• W2910368428 hasConceptScore W2910368428C99454951 @default.
• W2910368428 hasIssue "Suppl_1" @default.
• W2910368428 hasLocation W29103684281 @default.
• W2910368428 hasOpenAccess W2910368428 @default.
• W2910368428 hasPrimaryLocation W29103684281 @default.
• W2910368428 hasRelatedWork W1966551433 @default.
• W2910368428 hasRelatedWork W2045930772 @default.
• W2910368428 hasRelatedWork W2062064479 @default.
• W2910368428 hasRelatedWork W2292898285 @default.
• W2910368428 hasRelatedWork W2349679547 @default.
• W2910368428 hasRelatedWork W2397764800 @default.
• W2910368428 hasRelatedWork W2402857688 @default.
• W2910368428 hasRelatedWork W2414743797 @default.
• W2910368428 hasRelatedWork W3030231345 @default.
• W2910368428 hasRelatedWork W3031323949 @default.
• W2910368428 hasVolume "130" @default.
• W2910368428 isParatext "false" @default.
• W2910368428 isRetracted "false" @default.
• W2910368428 magId "2910368428" @default.
• W2910368428 workType "article" @default.