ARO-021:  Crenolanib联合化疗用于新诊断AML的研究

  • Crenolanib联合诱导化疗治疗新诊断FLT3突变型AML患者的III期临床试验。
  • 该项研究在美国、欧洲的多个中心进行。
  • 该项研究旨在评估crenolanib(与Rydapt®相比)在此类患者中的安全性和有效性。

有关该研究的更多信息,请访问研究网站 https://clinicaltrials.gov/ct2/show/NCT03258931

ARO-013: Crenolanib联合化疗用于复发/难治性AML的研究

  • Crenolanib联合挽救化疗治疗难治/复发性FLT3突变型AML患者的III期临床试验。
  • 该项研究将在美国、欧洲和中国的多个中心进行。
  • 该项研究旨在评估crenolanib(与安慰剂相比)在这类患者中的安全性和有效性。

有关该研究的更多信息,请访问研究网站 https://clinicaltrials.gov/ct2/show/NCT03250338

什么是急性髓性白血病(AML)?

急性髓系白血病是一种高度增殖型血液肿瘤,其特点是骨髓中产生异常髓系原始细胞。AML是成人中最常见的白血病类型,若不及时治疗,疾病将快速进展。

FMS 样酪氨酸激酶3(FLT3)概述

FLT3(FMS样酪氨酸激酶3)突变是AML中最常见的基因突变之一,约占AML患者总数的25-37%。目前已发现多种FLT3突变,这些突变是AML预后不良的标志。传统化疗对携带FLT3突变的肿瘤细胞通常疗效不佳。研究表明在标准化疗疗程中加入FLT3抑制剂比单用化疗产生更持久的益处。

THERE ARE SEVERAL ATTRIBUTES THAT SET CRENOLANIB APART FROM OTHER THERAPEUTIC OPTIONS

  1. Crenolanib, whether delivered by itself or as part of a drug combination, has shown benefit in FLT3 mutant AML.
  2. Patients who progress after treatment with prior TKIs may still remain sensitive to crenolanib.
  3. Crenolanib has favorable pharmacokinetics and does not accumulate with repeated dosing.
  4. Crenolanib is a selective type I TKI that does not inhibit wild-type cKIT.

Recent Conference Presentations

  1. Collins R, Kantarjian HM, Levis MJ, et al. Clinical Activity Of Crenolanib In Patients With D835 Mutant FLT3-Positive Relapsed/Refractory Acute Myeloid Leukemia (AML). J Clin Oncol 2014; 32:5s (suppl; abstr 7027).
  2. Collins, R., et al., Full Doses of Crenolanib, a Type I FLT3 Inhibitor, Can be Safely Administered in AML Patients Post Allogeneic Stem Cell Transplant. Blood, 2015. 126(23): p. 4359-4359.
  3. Panetta, J.C., et al., Population Pharmacokinetics of Crenolanib, a Type I FLT3 Inhibitor, in Patients with Relapsed/Refractory AML. Blood, 2015. 126(23): p. 3695-3695.
  4. Zhang, H., et al., Exome Sequencing Informs Mechanisms of Clinical Resistance to the FLT3-D835 Inhibitor Crenolanib. Blood, 2015. 126(23): p. 2468-2468.
  5. Inaba, H., et al., Pilot Study of Combined Type I FLT3 Tyrosine Kinase Inhibitor, Crenolanib with Sorafenib in Pediatric Patients with Relapsed/Refractory FLT3+Ve AML. Blood, 2016. 128(22): p. 3937-3937.
  6. Iyer, S.P., et al., Safety Study of Salvage Chemotherapy High-Dose Ara-C/Mitoxantrone (HAM) and Type I FLT3-TKI Crenolanib in First Relapsed/Primary Refractory AML. Blood, 2016. 128(22): p. 3983-3983.
  7. Ohanian, M., et al., Efficacy of a Type I FLT3 Inhibitor, Crenolanib, with Idarubicin and High-Dose Ara-C in Multiply Relapsed/Refractory FLT3+ AML. Blood, 2016. 128(22): p. 2744-2744.
  8. Wang, E.S., et al., Crenolanib, a Type I FLT3 TKI, Can be Safely Combined with Cytarabine and Anthracycline Induction Chemotherapy and Results in High Response Rates in Patients with Newly Diagnosed FLT3 Mutant Acute Myeloid Leukemia (AML). Blood, 2016. 128(22): p. 1071-1071.
  9. Cortes JE, Kantarjian HM, Kadia TM, et al. Crenolanib Besylate, a Type I Pan-FLT3 Inhibitor, to Demonstrate Clinical Activity in Multiply Relapsed FLT3-ITD and D835 AML. J Clin Oncol 2016; 34 (suppl; abstr 7008).
  10. Stone RM, Collins R, Tallman MS, et al. Effect of Cytarabine/Anthracycline/Crenolanib Induction on Minimal Residual Disease (MRD) in Newly Diagnosed FLT3 Mutant AML. J Clin Oncol 2017; 35(15_suppl): 7016.
  11. Wang E, Stone R, Collins R, Agrawal T, Urity V, Tallman M. Variant FLT3 Mutations Can be Eridicated by Cytarabine/Anthracycline/Crenolanib Induction in Adult Patients with Newly Diagnosed FLT3 (ITD/TKD) Mutant AML.  Haematologica; 2017; 2017. p. 212.
  12. Tarlock K, Hylkema T, Pollard J, et al. Functional Assessment of Novel Diagnostic FLT3 Mutations and Inhibition by Kinase Inhibitors. Haematologica; 2017; 2017. p. 40-1.

Recent Peer-reviewed Publications

  1. Zimmerman EI, Turner DC, Buaboonnam J, et al. Crenolanib is Active Against Models of Drug-Resistant FLT3-ITD-Positive Acute Myeloid Leukemia. Blood 2013; 122(22): 3607-15.
  2. Fathi AT. Emergence of Crenolanib for FLT3-Mutant AML. Blood 2013; 122(22): 3547-8.
  3. Smith CC, Lasater EA, Lin KC, et al. Crenolanib is a Selective Type I Pan-FLT3 Inhibitor. Proc Natl Acad Sci U S A 2014; 111(14): 5319-24.
  4. Zhang W, Gao C, Konopleva M, et al. Reversal of Acquired Drug Resistance in FLT3-Mutated Acute Myeloid Leukemia Cells via Distinct Drug Combination Strategies. Clin Cancer Res 2014; 20(9): 2363-74.
  5. Galanis A, Ma H, Rajkhowa T, et al. Crenolanib is a Potent Inhibitor of FLT3 with Activity Against Resistance-Conferring Point Mutants. Blood 2014; 123(1): 94-100.
  6. Smith CC, Lin K, Stecula A, Sali A, Shah NP. FLT3 D835 Mutations Confer Differential Resistance to Type II FLT3 Inhibitors. Leukemia 2015; 29(12): 2390-2.