A Study of ASP2215 Versus Salvage Chemotherapy In Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML) With FMS-like Tyrosine Kinase 3 (FLT3) Mutation

NCT03182244 | Active Not Recruiting Phase 3 Results DMC FDA Drug

• 2 other identifiers: 2215-CL-0303CTR20170326
• Study Type: interventional
• Target: 276
• Locations: 5 countries
• Sites: 49

Brief Summary

The purpose of this study was to determine the clinical benefit of ASP2215 therapy in participants with FMS-like tyrosine kinase (FLT3) mutated AML who were refractory to or had relapse after first-line AML therapy as shown with overall survival (OS) compared to salvage chemotherapy. In addition, this study evaluated safety as well as determined the overall efficacy in event-free survival (EFS) and complete remission (CR) rate of ASP2215 compared to salvage chemotherapy.

Conditions

AML With FLT3 Mutation

Keywords

gilteritinib; Acute Myeloid Leukemia (AML); ASP2215

Outcome Measures

Primary Outcomes (1)

• Overall Survival (OS)

  OS was defined as the time from the date of randomization to the date of death due to any cause. Participants who were still alive or lost to follow up were censored at the time they were last known to be alive. Kaplan-Meier (KM) estimates was used for analysis.

  From the date of randomization up to the date of death (up to approximatley 74 months)

Secondary Outcomes (24)

• Event-Free Survival (EFS)

  From the date of randomization up to the date of documented relapse, treatment failure or death from any cause, off-treatment relapse and start of new AML therapy (up to approximately 74 months)

• Complete Remission (CR) Rate

  From the date of randomization up to approximately 74 months

• Duration of CR

  From date of achieving CR until date of confirmed relapse (maximum duration was 53.4 months )

• Duration of Composite Complete Remission (CRc)

  From date of achieving CRc until date of confirmed relapse (maximum duration was 60 months)

• Duration of CR/Complete Remission With Partial Hematologic Recovery (CRh)

  From date of achieving CR/CRh until date of confirmed relapse (maximum duration was 58.1 months)

Study Arms (2)

Gilteritinib

EXPERIMENTAL

Participants received 120 milligrams (mg) gilteritinib (3 tablets of 40 mg) orally, once a day in continuous 28-day cycles until treatment discontinuation criteria were met. Participants who met the treatment discontinuation criteria, entered the long-term follow-up period. Participants remained in the long-term follow-up period for up to 3 years from the participant's end of treatment visit or until discontinuation from the study.

Drug: Gilteritinib

Salvage chemotherapy

ACTIVE COMPARATOR

Participants received salvage chemotherapy in continuous 28-day cycles per institutional guidelines:LoDAC:20mg cytarabine twice daily SC/IV for 10 days. MEC:mitoxantrone 6 milligrams per square meter(mg/m\^2)/day IV for 5 days (days 1 to 5), etoposide 100mg/m\^2/day IV for 5 days (days 1 to 5), cytarabine 1000mg/m\^2/day IV for 5 days (days 1 to 5). FLAG: granulocyte colony-stimulating factor (G-CSF) 300 micrograms per square meter (μg/m\^2) per day SC/IV for 5 days (days 1 to 5), fludarabine 30mg/m\^2/day IV for 5 days (days 2 to 6), cytarabine 2000mg/m\^2/day IV for 5 days (days 2 to 6). Participants meeting treatment discontinuation criteria, entered long-term follow-up, for up to 3 years from end of treatment visit/until study discontinuation. Based on interim analysis outcome, at investigators discretion, treatment period participants had option to enter crossover extension to receive 120mg gilteritinib, orally, once daily in continuous 28-day cycles until treatment discontinuation.

Drug: Cytarabine; Drug: Mitoxantrone; Drug: Etoposide; Drug: G-CSF; Drug: Fludarabine

Interventions

Gilteritinib DRUG

Tablet administered orally once daily.

Also known as: ASP2215

Gilteritinib

Cytarabine DRUG

Once/twice daily Intravenously (IV)/subcutaneously (SC).

Salvage chemotherapy

Mitoxantrone DRUG

Once daily IV injection.

Salvage chemotherapy

Etoposide DRUG

Once daily IV injection.

Salvage chemotherapy

G-CSF DRUG

Once daily IV/SC injection.

Salvage chemotherapy

Fludarabine DRUG

Once daily IV injection.

Salvage chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant has a diagnosis of primary AML or AML secondary to myelodysplastic syndrome (MDS) according to World Health Organization (WHO) classification as determined by pathology review at the treating institution.
• Participant is refractory to or relapsed after first-line AML therapy (with or without HSCT)
• Refractory to first-line AML therapy is defined as:
• a. Participant did not achieve CR/CRi/CRp under initial therapy. A participant eligible for standard therapy must receive at least 1 cycle of an anthracycline containing induction block in standard dose for the selected induction regimen. A participant not eligible for standard therapy must have received at least 1 complete block of induction therapy seen as the optimum choice of therapy to induce remission for this participant.
• Untreated first hematologic relapse is defined as:
• Participant must have achieved a CR/CRi/CRp with first-line treatment and has hematologic relapse.
• Participant is positive for FLT3 mutation in bone marrow or whole blood as determined by the central lab. A participant with rapidly proliferative disease and unable to wait for the central lab results can be enrolled based on a local test performed after completion of the last interventional treatment. Participants can be enrolled from a local test result if the participants have any of the following FLT3 mutations: FLT3-internal tandem duplication (ITD), FLT3-tyrosine kinase domain (TKD)/D835 or FLT3-TKD/I836.
• Participant has an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
• Participant is eligible for preselected salvage chemotherapy.
• Participant must meet the following criteria as indicated on the clinical laboratory tests:
• Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x upper limit of normal (ULN)
• Serum total bilirubin (TBL) ≤ 1.5 x ULN
• Serum creatinine ≤ 1.5 x ULN or an estimated glomerular filtration rate of \> 50 mL/min as calculated by the Modification of Diet in Renal Disease equation.
• Participant is suitable for oral administration of study drug.
• Participant agrees not to participate in another interventional study while on treatment.

You may not qualify if:

• Participant was diagnosed as acute promyelocytic leukemia.
• Participant has BCR-ABL-positive leukemia (chronic myelogenous leukemia in blast crisis).
• Participant has AML secondary to prior chemotherapy for other neoplasms (except for MDS).
• Participant is in second or later hematologic relapse or has received salvage therapy for refractory disease.
• Participant has clinically active central nervous system leukemia..
• Participant has been diagnosed with another malignancy, unless disease-free for at least 5 years. Participants with treated nonmelanoma skin cancer, in situ carcinoma or cervical intraepithelial neoplasia, regardless of the disease-free duration, are eligible for this study if definitive treatment for the condition has been completed. Participants with organ-confined prostate cancer with no evidence of recurrent or progressive disease are eligible if hormonal therapy has been initiated or the malignancy has been surgically removed or treated with definitive radiotherapy.
• Participant has received prior treatment with ASP2215 or other FLT3 inhibitors (with the exception of sorafenib and midostaurin used in first-line therapy regimen as part of induction, consolidation and/or maintenance).
• Participant has clinically significant abnormality of coagulation profile, such as disseminated intravascular coagulation.
• Participant has had major surgery within 4 weeks prior to the first study dose.
• Participant has radiation therapy within 4 weeks prior to the first study dose.
• Participant has congestive heart failure New York Heart Association (NYHA) class 3 or 4 or participant with a history of congestive heart failure NYHA class 3 or 4 in the past, unless a screening echocardiogram (ECHO) performed within 1 month prior to study entry results in a left ventricular ejection fraction (LVEF) that is ≥ 45%.
• Participant with mean of triplicate Fridericia-corrected QT interval (QTcF) \> 450 ms at Screening based on central reading.
• Participant with Long QT Syndrome at Screening.
• Participant with hypokalemia and hypomagnesemia at Screening (defined as values below lower limit of normal \[LLN\]).
• Participant requires treatment with concomitant drugs that are strong inducers of CYP3A.

Sponsors & Collaborators

• Astellas Pharma Inc: lead

Study Sites (49)

Site CN103

Beijing, China

Location

Site CN108

Beijing, China

Location

Site CN109

Beijing, China

Location

Site CN110

Beijing, China

Location

Site CN131

Beijing, China

Location

Site CN116

Changchun, China

Location

Site CN120

Changsha, China

Location

Site CN119

Fuzhou, China

Location

Site CN102

Guangzhou, China

Location

Site CN114

Guangzhou, China

Location

Site CN121

Guangzhou, China

Location

Site CN130

Guiyang, China

Location

Site CN107

Hangzhou, China

Location

Site CN118

Hefei, China

Location

Site CN123

Huangpu Qu, China

Location

Site CN117

Jinan, China

Location

Site CN133

Lanzhou, China

Location

Site CN128

Nanjing, China

Location

Site CN106

Qingdao, China

Location

Site CN126

Shanghai, China

Location

Site CN129

Shanghai, China

Location

Site CN125

Shenyang, China

Location

Site CN101

Tianjin, China

Location

Site CN105

Wuhan, China

Location

Site CN122

Xi'an, China

Location

Site CN132

Zhangzhou, China

Location

Site CN113

Zhengzhou, China

Location

Site CN136

Zhengzhou, China

Location

Site MY306

Ampang, Malaysia

Location

Site MY305

George Town, Malaysia

Location

Site MY301

Johor Bahru, Malaysia

Location

Site MY304

Kota Kinabalu, Malaysia

Location

Site MY302

Kuala Lumpur, Malaysia

Location

Site MY303

Pulau Pinang, Malaysia

Location

Site RU506

Kemerovo, Russia

Location

Site RU504

Krasnoyarsk, Russia

Location

Site RU508

Moscow, Russia

Location

Site RU509

Moscow, Russia

Location

Site RU501

Saint Petersburg, Russia

Location

Site RU502

Saint Petersburg, Russia

Location

Site RU507

Saint Petersburg, Russia

Location

Site SG401

Singapore, Singapore

Location

Site SG402

Singapore, Singapore

Location

Site SG403

Singapore, Singapore

Location

Site TH203

Bangkok, Thailand

Location

Site TH205

Bangkok, Thailand

Location

Site TH204

Chiang Mai, Thailand

Location

Site TH201

Khon Kaen, Thailand

Location

Site TH202

Khon Kaen, Thailand

Location

Related Publications (1)

• Jiang B, Li J, Liu L, Du X, Jiang H, Hu J, Zeng X, Sakatani T, Kosako M, Deng Y, Girshova L, Bondarenko S, Lee LWL, Khuhapinant A, Martynova E, Hasabou N, Wang J. Gilteritinib versus salvage chemotherapy in predominantly Asian patients with relapsed/refractory FLT3-mutated acute myeloid leukemia: a regional analysis of COMMODORE in China, South-East Asia, and Russia. Ann Hematol. 2025 Mar;104(3):1563-1575. doi: 10.1007/s00277-025-06235-y. Epub 2025 Mar 10.

  PMID: 40063243 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

gilteritinib; Cytarabine; Mitoxantrone; Etoposide; Granulocyte Colony-Stimulating Factor; fludarabine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Anthraquinones; Anthrones; Anthracenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Quinones; Polycyclic Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Glucosides; Glycosides; Carbohydrates; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Results Point of Contact

• Title: Clinical Transparency
• Organization: Astellas Pharma Inc

astellas.resultsdisclosure@astellas.com

+81 3-3244-6500 Japanese only

Study Officials

• Medical Director

  Astellas Pharma Inc

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 8, 2017
• First Posted: June 9, 2017
• Study Start: October 25, 2017
• Primary Completion: December 25, 2023
• Study Completion (Estimated): March 31, 2027
• Last Updated: May 5, 2026
• Results First Posted: January 14, 2025

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.
• Access Criteria: Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.

Locations

TH (5); RU (7); SG (3); CN (28); MY (6)