A phase 1b study of glasdegib + azacitidine in patients with untreated acute myeloid leukemia and higher-risk myelodysplastic syndromes.
Acute myeloid leukemia
Chronic myelomonocytic syndromes
Clinical trials
Glasdegib
Myelodysplastic syndromes
Journal
Annals of hematology
ISSN: 1432-0584
Titre abrégé: Ann Hematol
Pays: Germany
ID NLM: 9107334
Informations de publication
Date de publication:
Aug 2022
Aug 2022
Historique:
received:
12
01
2022
accepted:
20
04
2022
pubmed:
1
5
2022
medline:
16
7
2022
entrez:
30
4
2022
Statut:
ppublish
Résumé
This phase 1b study evaluated glasdegib (100 mg once daily) + azacitidine in adults with newly diagnosed acute myeloid leukemia (AML), higher-risk myelodysplastic syndromes (MDS), or chronic myelomonocytic leukemia (CMML) who were ineligible for intensive chemotherapy. Of 72 patients enrolled, 12 were in a lead-in safety cohort (LIC) and 60 were in the AML and MDS (including CMML) expansion cohorts. In the LIC, the safety profile of glasdegib + azacitidine was determined to be consistent with those of glasdegib or azacitidine alone, with no evidence of drug-drug interaction. In the expansion cohort, the most frequently (≥ 10%) reported non-hematologic Grade ≥ 3 treatment-emergent adverse events were decreased appetite, electrocardiogram QT prolongation, and hypertension in the AML cohort and sepsis, diarrhea, hypotension, pneumonia, and hyperglycemia in the MDS cohort. Overall response rates in the AML and MDS cohorts were 30.0% and 33.3%, respectively; 47.4% and 46.7% of patients who were transfusion dependent at baseline achieved independence. Median overall survival (95% confidence interval) was 9.2 (6.2-14.0) months and 15.8 (9.3-21.9) months, respectively, and response was associated with molecular mutation clearance. Glasdegib + azacitidine in patients with newly diagnosed AML or MDS demonstrated an acceptable safety profile and preliminary evidence of clinical benefits.Trial registration: ClinicalTrials.gov NCT02367456.
Identifiants
pubmed: 35488900
doi: 10.1007/s00277-022-04853-4
pii: 10.1007/s00277-022-04853-4
doi:
Substances chimiques
Benzimidazoles
0
Phenylurea Compounds
0
glasdegib
K673DMO5H9
Azacitidine
M801H13NRU
Banques de données
ClinicalTrials.gov
['NCT02367456']
Types de publication
Clinical Trial, Phase I
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1689-1701Subventions
Organisme : Medical Research Council
ID : MC_UU_00016/11
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00029/8
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_U137961146
Pays : United Kingdom
Organisme : Medical Research Council
ID : G1000729
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_19049
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/L008963/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12009/11
Pays : United Kingdom
Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
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