Phase I/II study of dasatinib in combination with decitabine in patients with accelerated or blast phase chronic myeloid leukemia.

Szczegóły
Abstrakt

Tytuł:: Phase I/II study of dasatinib in combination with decitabine in patients with accelerated or blast phase chronic myeloid leukemia.
Autorzy:: Abaza Y; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Kantarjian H; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Alwash Y; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Borthakur G; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Champlin R; Department of Stem Cell Transplant, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Kadia T; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Garcia-Manero G; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Daver N; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Ravandi F; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Verstovsek S; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Burger J; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Estrov Z; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Ohanian M; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Lim M; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Pemmaraju N; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Jabbour E; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Cortes J; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.; Georgia Cancer Center, Augusta University, Augusta, Georgia.
Źródło:: American journal of hematology [Am J Hematol] 2020 Nov; Vol. 95 (11), pp. 1288-1295. Date of Electronic Publication: 2020 Aug 12.
Typ publikacji:: Clinical Trial, Phase I; Clinical Trial, Phase II; Journal Article; Randomized Controlled Trial; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
Język:: English
Imprint Name(s):: Publication: New York Ny : Wiley-Blackwell
Original Publication: New York, Liss.
MeSH Terms:: Blast Crisis*/blood
Blast Crisis*/drug therapy
Blast Crisis*/mortality
Leukemia, Myelogenous, Chronic, BCR-ABL Positive*/blood
Leukemia, Myelogenous, Chronic, BCR-ABL Positive*/drug therapy
Leukemia, Myelogenous, Chronic, BCR-ABL Positive*/mortality
Antineoplastic Combined Chemotherapy Protocols/*administration & dosage
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Dasatinib/administration & dosage ; Dasatinib/adverse effects ; Decitabine/administration & dosage ; Decitabine/adverse effects ; Disease-Free Survival ; Female ; Humans ; Leukemia, Myeloid, Acute/blood ; Leukemia, Myeloid, Acute/drug therapy ; Leukemia, Myeloid, Acute/mortality ; Male ; Middle Aged ; Survival Rate
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Grant Information:: CA016672 International University of Texas MD Anderson Cancer Center
Substance Nomenclature:: 776B62CQ27 (Decitabine)
RBZ1571X5H (Dasatinib)
Entry Date(s):: Date Created: 20200719 Date Completed: 20201229 Latest Revision: 20201229
Update Code:: 20240105
DOI:: 10.1002/ajh.25939
PMID:: 32681739
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Treatment of advanced-phase chronic myeloid leukemia (CML) remains unsatisfactory. Single-agent tyrosine kinase inhibitors have modest and short-lived activity in this setting. We conducted a phase I/II study to determine safety and efficacy of the combination of dasatinib and decitabine in patients with advanced CML. Two different dose schedules were investigated with a starting decitabine dose of either 10 mg/m 2 or 20 mg/m 2 daily for 10 days plus dasatinib 100 mg daily. The target dose level was decitabine 10 mg/m 2 or 20 mg/m 2 daily for 10 days plus dasatinib 140 mg daily. Thirty patients were enrolled, including seven with accelerated-phase CML, 19 with blast-phase CML, and four with Philadelphia-chromosome positive acute myeloid leukemia. No dose-limiting toxicity was observed at the starting dose level with either schedule. Grade ≥3 treatment emergent hematological adverse events were reported in 28 patients. Thirteen patients (48%) achieved a major hematologic response and six (22%) achieved a minor hematologic response, with 44% of these patients achieving a major cytogenetic response and 33% achieving a major molecular response. Median overall survival (OS) was 13.8 months, with significantly higher OS among patients who achieved a hematologic response compared to non-responders (not reached vs 4.65 months; P < .001). Decitabine plus dasatinib is a safe and active regimen in advanced CML. Further studies using this combination are warranted.
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