A randomized phase 2 trial of nintedanib and low-dose cytarabine in elderly patients with acute myeloid leukemia ineligible for intensive chemotherapy

被引:0
作者
Andrew F. Berdel
Raphael Koch
Joachim Gerss
Marcus Hentrich
Rudolf Peceny
Tobias Bartscht
Björn Steffen
Marina Bischoff
Karsten Spiekermann
Linus Angenendt
Jan-Henrik Mikesch
Tobias Kewitz
Trude Butterfass-Bahloul
Hubert Serve
Georg Lenz
Wolfgang E. Berdel
Utz Krug
Christoph Schliemann
机构
[1] University Hospital Münster,Department of Medicine A
[2] University of Münster,Institute of Biostatistics and Clinical Research
[3] Red Cross Hospital,Department of Hematology and Oncology
[4] Hematology and Stem Cell Transplantation,Department of Oncology
[5] University Hospital Lübeck,Department of Medicine I
[6] University Hospital Frankfurt,Department of Medicine II
[7] Klinikum Idar-Oberstein,Department of Hematology and Oncology
[8] University Hospital Munich,Department of Medicine III
[9] Ludwig-Maximilians-University,Centre for Clinical Trials
[10] University of Münster,Department of Medicine
[11] III,undefined
[12] Hospital Leverkusen,undefined
来源
Annals of Hematology | 2023年 / 102卷
关键词
Acute myeloid leukemia; Nintedanib; Low-dose cytarabine; Angiogenesis;
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学科分类号
摘要
We investigated the safety and efficacy of nintedanib added to low-dose cytarabine (LDAC) in a phase 1/2 study in patients 60 years or older with newly diagnosed or relapsed/refractory (r/r) AML ineligible for intensive chemotherapy. The results of the dose-finding phase 1 part have been previously published. Patients were randomized 1:1 to LDAC plus nintedanib or LDAC plus placebo stratified by AML status (newly diagnosed vs r/r). LDAC was applied subcutaneously at 20 mg twice daily on days 1 to 10. Nintedanib/placebo was orally administered twice daily on days 1 to 28 in 28-day cycles. The primary endpoint was overall survival (OS). Between 05/2017 and 09/2019, 31 patients were randomized and 30 were treated, before the study was terminated prematurely due to slow recruitment. Median (range) age of patients was 76 (60–84) years. Twenty-two patients (73%) had r/r AML. Median OS in patients treated with LDAC and nintedanib was 3.4 months, compared with 3.6 months in those treated in the placebo arm, with a HR adjusted for AML status of 1.19 (corresponding confirmatory adjusted 95% CI, 0.55–2.56; univariate log-rank P = 0.96). In the 22 patients with r/r AML, median OS was 3.0 months in the nintedanib and 3.6 months in the placebo arm (P = 0.36). One patient in the nintedanib and two patients in the placebo arm achieved a CR and entered maintenance treatment. Nintedanib showed no superior therapeutic activity over placebo when added to LDAC in elderly AML patients considered unfit for intensive chemotherapy. The trial was registered at clinicaltrials.gov NCT01488344.
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页码:63 / 72
页数:9
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