Results of a phase 1 study of quizartinib as maintenance therapy in subjects with acute myeloid leukemia in remission following allogeneic hematopoietic stem cell transplant
| Autor: | Brenda M. Sandmaier, Denise Trone, Guy Gammon, Betul Oran, Samer K. Khaled, Olga Frankfurt |
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| Rok vydání: | 2017 |
| Předmět: |
Adult
medicine.medical_specialty Maximum Tolerated Dose Neutropenia Gastroenterology Maintenance Chemotherapy 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Maintenance therapy Quizartinib Dihydrochloride Recurrence Internal medicine hemic and lymphatic diseases Medicine Humans Transplantation Homologous Benzothiazoles Research Articles Quizartinib Leukopenia business.industry Phenylurea Compounds Remission Induction Hematopoietic Stem Cell Transplantation Hematology medicine.disease Surgery Transplantation Leukemia Myeloid Acute Tolerability chemistry fms-Like Tyrosine Kinase 3 030220 oncology & carcinogenesis Eye disorder medicine.symptom business 030215 immunology Research Article |
| Zdroj: | American Journal of Hematology |
| ISSN: | 1096-8652 |
| Popis: | FLT3-ITD–mutated acute myeloid leukemia (AML) has very high risk of relapse and is associated with poor outcome following allogeneic hematopoietic-cell transplant (allo-HCT). This two-part, phase 1, multicenter, open-label, sequential-group, dose-escalation study aimed to determine dose-limiting toxicities (DLTs), maximum tolerated dose (MTD), and safety/tolerability of quizartinib, a selective and highly potent FLT3 inhibitor, when administered as maintenance therapy after allo-HCT. Thirteen subjects with documented FLT3-ITD–mutated AML in morphological remission following allo-HCT received one of two quizartinib dihydrochloride dose levels (DL): 40 mg/d (DL1; n=7) and 60 mg/d (DL2; n=6), administered orally in 28-day cycles for up to 24 cycles. Median age of participants was 43 years. All subjects received human leukocyte antigen (HLA)-matched allo-HCT. One subject treated at DL1 and 1 treated at DL2 had DLTs that required drug interruption (grade 3 gastric hemorrhage and grade 3 anemia, respectively). Ten subjects (77%) received quizartinib for >1 year; 5 (38%) completed 24 cycles. Four subjects (31%) discontinued quizartinib due to adverse events. One subject (8%) experienced relapse during cycle 1 and discontinued treatment. Most common (≥20%) grade 3/4 adverse events were neutropenia (23%), anemia (15%), leukopenia (15%), lymphopenia (15%), and eye disorders (15%). This study demonstrated acceptable tolerability and early evidence of reduced relapse rate following allo-HCT with quizartinib maintenance compared to historical cohorts. No MTD was identified, but 60 mg daily was selected as highest dose for continuous daily administration based on randomized comparison of daily 30 and 60 mg doses in relapsed/refractory AML. This article is protected by copyright. All rights reserved. |
| Databáze: | OpenAIRE |
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