scholarly journals Clinical profile of gilteritinib in Japanese patients with relapsed/refractory acute myeloid leukemia: An open-label phase 1 study

2018 ◽  
Vol 109 (10) ◽  
pp. 3235-3244 ◽  
Author(s):  
Kensuke Usuki ◽  
Toru Sakura ◽  
Yukio Kobayashi ◽  
Toshihiro Miyamoto ◽  
Hiroatsu Iida ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Phase 1 ◽  
Japanese Patients ◽  
Clinical Profile ◽  
Open Label ◽  
Phase 1 Study ◽  
Open Label Phase ◽  
Refractory Acute Myeloid Leukemia ◽  
Acute Myeloid

scholarly journals Phase 1b study of the MDM2 inhibitor AMG 232 with or without trametinib in relapsed/refractory acute myeloid leukemia

2019 ◽  
Vol 3 (13) ◽  
pp. 1939-1949 ◽  
Author(s):  
Harry P. Erba ◽  
Pamela S. Becker ◽  
Paul J. Shami ◽  
Michael R. Grunwald ◽  
Donna L. Flesher ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Target Genes ◽  
Phase 1 ◽  
Maximum Tolerated Dose ◽  
Clinical Activity ◽  
Open Label ◽  
Refractory Acute Myeloid Leukemia ◽  
Higher Doses ◽  
Acute Myeloid

AbstractThis open-label, phase 1 study evaluated the safety, pharmacokinetics, and maximum tolerated dose of AMG 232, an investigational oral, selective mouse double minute 2 homolog inhibitor in relapsed/refractory acute myeloid leukemia (AML). AMG 232 was administered orally once daily for 7 days every 2 weeks (7 on/off) at 60, 120, 240, 360, 480, or 960 mg as monotherapy (arm 1) or at 60 mg with trametinib 2 mg (arm 2). Dose-limiting toxicities (DLTs), adverse events (AEs), pharmacokinetics, clinical and pharmacodynamic response, and expression of p53 target genes were assessed. All 36 patients received AMG 232. No DLTs occurred in arm 1, and 360 mg was the highest test dose; dose escalation was halted due to gastrointestinal AEs at higher doses. One of ten patients in arm 2 had a DLT (grade 3 fatigue); 60 mg was the highest dose tested with trametinib. Common treatment-related AEs (any grade) included nausea (58%), diarrhea (56%), vomiting (33%), and decreased appetite (25%). AMG 232 exhibited linear pharmacokinetics unaffected by coadministration with trametinib. Serum macrophage inhibitor cytokine-1 and bone marrow expression of BAX, PUMA, P21, and MDM2 increased during treatment. Of 30 evaluable patients, 1 achieved complete remission, 4 had morphologic leukemia-free state, and 1 had partial remission. Four of 13 (31%) TP53-wild-type patients and 0 of 3 (0%) TP53-mutant patients were responders. AMG 232 was associated with gastrointestinal AEs at higher doses but had acceptable pharmacokinetics, on-target effects, and promising clinical activity warranting further investigation in patients with relapsed/refractory AML. This trial was registered at www.clinicaltrials.gov as #NCT02016729.

Phase 1 study of CWP232291 in relapsed/refractory acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS).

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. 7044-7044 ◽  
Author(s):  
Jorge E. Cortes ◽  
Stefan Faderl ◽  
John Pagel ◽  
Chul Won Jung ◽  
Sung-Soo Yoon ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myelodysplastic Syndrome ◽  
Myeloid Leukemia ◽  
Phase 1 ◽  
Phase 1 Study ◽  
Refractory Acute Myeloid Leukemia ◽  
Acute Myeloid
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