A phase 3 randomized study of gilteritinib versus salvage chemotherapy in FLT3 mutation-positive subjects with relapsed or refractory acute myeloid...

Date 24 November 2018
Event ESMO Asia 2018 Congress
Session Poster display - Cocktail
Topics Leukaemia
Anticancer Agents
Personalised/Precision Medicine
Presenter Jianxing Wang
Citation Annals of Oncology (2018) 29 (suppl_9): ix87-ix93. 10.1093/annonc/mdy437
Authors J. Wang1, J. Li2, A. Tantiworawit3, S. Izuka4, S. Yamada4, J. Hill5, E. Shima Rich5, E. Bahceci5
  • 1Institute Of Hematology, Chinese Academy of Medical Sciences, 300000 - Tianjin/CN
  • 2Shanghai Jiao Tong University School Of Medicine, Ruijin Hospital, Shanghai/CN
  • 3Faculty Of Medicine, Maharaj Nakorn Chiang Mai Hospital, Chiang Mai/TH
  • 4Global Development, Astellas Pharma, Inc., Tokyo/JP
  • 5Global Development, Astellas Pharma, Inc., Northbrook/US

Abstract

Background

The highly potent, selective fms-like tyrosine kinase 3 (FLT3)/AXL inhibitor, gilteritinib (ASP2215), showed strong antileukemic activity at doses ≥80 mg/day in patients with FLT3 mutation-positive (FLT3Mut+) relapsed/refractory (R/R) acute myeloid leukemia (AML). This phase 3 trial was designed to compare the efficacy and safety of gilteritinib versus salvage chemotherapy in FLT3Mut+ subjects with R/R AML.

Trial design

This phase 3, open-label randomized multicenter trial (NCT03182244) will enroll approximately 320 adult subjects (aged ≥18 years; Eastern Cooperative Oncology Group [ECOG] performance status ≤2) with FLT3Mut+ R/R AML from ∼50 centers across China, Russia, Singapore, Thailand, and Malaysia. Subjects will be randomized (1:1) to receive 28-day cycles of once-daily oral gilteritinib (120 mg) or salvage chemotherapy. The salvage chemotherapy regimen will be selected by the investigator from the following predetermined options: LoDAC (intravenous [IV]/subcutaneous [SC] cytarabine 20 mg BID for 10 days), MEC (IV mitoxantrone 6 mg/m2/d plus IV etoposide 100 mg/m2/d plus IV cytarabine 1000 mg/m2/d, Days 1–5), or FLAG (granulocyte colony-stimulating factor SC/IV 300 μg/m2/d, Days 1–5; IV fludarabine 30 mg/m2/d, Days 2–6; IV cytarabine 2000 mg/m2/d, Days 2–6). Subjects receiving gilteritinib or LoDAC will continue treatment until a discontinuation criterion is met; those receiving MEC or FLAG will be assessed for response on or after Day 15 of Cycle 1 and will receive a second cycle of MEC/FLAG chemotherapy if bone marrow (BM) cellularity is ≥ 20% with ≥50% reduction in BM blasts. If BM cellularity is > 5% to < 20%, the decision to administer a second cycle of MEC/FLAG chemotherapy will be made by the investigator. The primary endpoint is overall survival; key secondary endpoints are event-free survival and complete remission rate. Safety endpoints include the incidence of adverse events, results from laboratory investigations and vital sign examinations, findings from electrocardiograms, and changes in ECOG performance status. A formal interim analysis is planned when approximately 50% of deaths have occurred.

Editorial acknowledgement

Writing and editorial assistance by Kalpana Vijayan, PhD (SuccinctChoice Medical Communications, Chicago, IL).

Clinical trial identification

NCT03182244.

Legal entity responsible for the study

Astellas Pharma, Inc.

Funding

Astellas Pharma, Inc.

Disclosure

S. Izuka, S. Yamada, E. Shima Rich, E. Bahceci: Employee: Astellas Pharma Inc. J. Hill: Employee: Astellas Pharma Inc.; Holds patents and stocks: Lagacept, LLC. All other authors have declared no conflicts of interest.