A phase I trial of selinexor plus FLAG-Ida for the treatment of refractory/relapsed adult acute myeloid leukemia patients.
Adult
Antineoplastic Combined Chemotherapy Protocols
/ administration & dosage
Cytarabine
/ administration & dosage
Granulocyte Colony-Stimulating Factor
/ administration & dosage
Humans
Hydrazines
/ administration & dosage
Idarubicin
/ administration & dosage
Leukemia, Myeloid, Acute
/ drug therapy
Male
Maximum Tolerated Dose
Middle Aged
Neoplasm Recurrence, Local
/ drug therapy
Treatment Outcome
Triazoles
/ administration & dosage
Vidarabine
/ administration & dosage
AML
FLAG-Ida
KPT-330
Relapsed/refractory
Selinexor
XPO1
Journal
Annals of hematology
ISSN: 1432-0584
Titre abrégé: Ann Hematol
Pays: Germany
ID NLM: 9107334
Informations de publication
Date de publication:
Jun 2021
Jun 2021
Historique:
received:
12
03
2021
accepted:
19
04
2021
pubmed:
30
4
2021
medline:
27
5
2021
entrez:
29
4
2021
Statut:
ppublish
Résumé
Prognosis for relapsed or refractory (R/R) acute myeloid leukemia (AML) despite salvage therapy is dismal. This phase I dose-escalation trial assessed the safety and preliminary clinical activity of selinexor, an oral exportin-1 (XPO1) inhibitor, in combination with FLAG-Ida in younger R/R AML patients. The aim was to find the recommended phase 2 dose (RP2D) and maximum tolerated dose (MTD). Fourteen patients were included, and selinexor dosage was 60 mg (3 patients), 80 mg (3 patients), and 100 mg (7 patients) weekly. No dose-limiting toxicities were reported. Grade ≥3 non-hematologic adverse events (AEs) occurred in 78.6% of patients. Two patients were non MTD evaluable due to early death, and overall, 3 out of 14 patients (21.4%) had fatal AEs. Five out of 12 (42%) response and MTD evaluable patients achieved a complete remission (CR; n=4) or CR with incomplete hematologic recovery (CRi, n=1), and 4 patients (33%) subsequently underwent allogeneic transplantation. The median overall survival (OS) and event-free survival (EFS) were 6.0 (range 0.9-19.3) and 1.1 months (range 0.7-19.3), respectively. Using selinexor 100 mg/weekly, CR/CRi rate of 66.7%, OS 13.6 months (range, 1.6-19.3), and EFS 10.6 months (range, 0.9-19.3). At last follow-up, 3 patients were alive. Selinexor 100 mg/weekly with FLAG-Ida combination in R/R AML showed acceptable tolerability and efficacy, establishing the RP2D of this regimen in future clinical trials. ClinicalTrials.gov Identifier: NCT03661515.
Identifiants
pubmed: 33914097
doi: 10.1007/s00277-021-04542-8
pii: 10.1007/s00277-021-04542-8
doi:
Substances chimiques
Hydrazines
0
Triazoles
0
Cytarabine
04079A1RDZ
Granulocyte Colony-Stimulating Factor
143011-72-7
selinexor
31TZ62FO8F
Vidarabine
FA2DM6879K
Idarubicin
ZRP63D75JW
Banques de données
ClinicalTrials.gov
['NCT03661515']
Types de publication
Clinical Trial, Phase I
Journal Article
Multicenter Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
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