دورية أكاديمية
Phase 1-2a multicenter dose-escalation study of ezatiostat hydrochloride liposomes for injection (Telintra, TLK199), a novel glutathione analog prodrug in patients with myelodysplastic syndrome
| العنوان: | Phase 1-2a multicenter dose-escalation study of ezatiostat hydrochloride liposomes for injection (Telintra, TLK199), a novel glutathione analog prodrug in patients with myelodysplastic syndrome |
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| المؤلفون: | Raza, Azra, Galili, Naomi, Callander, Natalie, Ochoa, Leonel, Piro, Lawrence, Emanuel, Peter, Williams, Stephanie, Burris, Howard, Faderl, Stefan, Estrov, Zeev, Curtin, Peter, Larson, Richard A., Keck, James G., Jones, Marsha, Meng, Lisa, Brown, Gail L. |
| المساهمون: | Internal Medicine |
| المصدر: | Journal of hematology and oncology ; 2 ; 20 |
| سنة النشر: | 2022 |
| المجموعة: | University of Massachusetts, Medical School: eScholarship@UMMS |
| مصطلحات موضوعية: | Life Sciences, Medicine and Health Sciences |
| الوصف: | BACKGROUND: Ezatiostat hydrochloride liposomes for injection, a glutathione S-transferase P1-1 inhibitor, was evaluated in myelodysplastic syndrome (MDS). The objectives were to determine the safety, pharmacokinetics, and hematologic improvement (HI) rate. Phase 1-2a testing of ezatiostat for the treatment of MDS was conducted in a multidose-escalation, multicenter study. Phase 1 patients received ezatiostat at 5 dose levels (50, 100, 200, 400 and 600 mg/m2) intravenously (IV) on days 1 to 5 of a 14-day cycle until MDS progression or unacceptable toxicity. In phase 2, ezatiostat was administered on 2 dose schedules: 600 mg/m2 IV on days 1 to 5 or days 1 to 3 of a 21-day treatment cycle. RESULTS: 54 patients with histologically confirmed MDS were enrolled. The most common adverse events were grade 1 or 2, respectively, chills (11%, 9%), back pain (15%, 2%), flushing (19%, 0%), nausea (15%, 0%), bone pain (6%, 6%), fatigue (0%, 13%), extremity pain (7%, 4%), dyspnea (9%, 4%), and diarrhea (7%, 4%) related to acute infusional hypersensitivity reactions. The concentration of the primary active metabolites increased proportionate to ezatiostat dosage. Trilineage responses were observed in 4 of 16 patients (25%) with trilineage cytopenia. Hematologic Improvement-Erythroid (HI-E) was observed in 9 of 38 patients (24%), HI-Neutrophil in 11 of 26 patients (42%) and HI-Platelet in 12 of 24 patients (50%). These responses were accompanied by improvement in clinical symptoms and reductions in transfusion requirements. Improvement in bone marrow maturation and cellularity was also observed. CONCLUSION: Phase 2 studies of ezatiostat hydrochloride liposomes for injection in MDS are supported by the tolerability and HI responses observed. An oral formulation of ezatiostat hydrochloride tablets is also in phase 2 clinical development. TRIAL REGISTRATION: Clinicaltrials.gov: NCT00035867. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | Link to Article in PubMed; J Hematol Oncol. 2009 May 13;2:20. Link to article on publisher's site; 1756-8722 (Linking); http://hdl.handle.net/20.500.14038/39358Test; https://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=3156&context=oapubs&unstamped=1Test; https://escholarship.umassmed.edu/oapubs/2157Test; 1257934; oapubs/2157 |
| DOI: | 10.1186/1756-8722-2-20 |
| الإتاحة: | https://doi.org/10.1186/1756-8722-2-20Test https://doi.org/20.500.14038/39358Test https://hdl.handle.net/20.500.14038/39358Test https://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=3156&context=oapubs&unstamped=1Test https://escholarship.umassmed.edu/oapubs/2157Test |
| حقوق: | © 2009 Raza et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0Test), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
| رقم الانضمام: | edsbas.DD87310B |
| قاعدة البيانات: | BASE |
| DOI: | 10.1186/1756-8722-2-20 |
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