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

NCT ID: NCT03182244

Last Updated: 2025-10-27

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 276 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-10-25
• Study Completion Date: 2026-03-31

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.

Detailed Description

Participants considered an adult according to local regulations at the time of signing informed consent were randomized in a 1:1 ratio and received ASP2215 or salvage chemotherapy. Participants entered the screening period up to 14 days prior to the start of treatment. Prior to randomization, the investigator preselected a salvage chemotherapy regimen for each participant; options included low-dose cytarabine (LoDAC), mitoxantrone, etoposide and intermediate-dose cytarabine (MEC) or fludarabine, high-dose cytarabine and granulocyte colony-stimulating factor (FLAG). The randomization was stratified by response to first-line therapy and preselected salvage chemotherapy. Participants were administered treatment over continuous 28-day cycles.

Among the participants, approximately 20 Chinese participants who were randomized into the ASP2215 arm were allocated to the pharmacokinetic (PK) cohort. Participants in the PK cohort were requested to be hospitalized from the date of randomization (Day 1) to at least the completion of all the assessments planned on Day 2. All participants in the PK cohort underwent blood sampling for PK measurement of ASP2215. Participants in PK cohort were administered the study drug in the same manner and underwent the same efficacy and safety assessments as other participants except for blood sampling for additional PK measurements.

Conditions

AML With FLT3 Mutation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Gilteritinib

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.

Group Type: EXPERIMENTAL

Gilteritinib

Intervention Type: DRUG

Tablet administered orally once daily.

Salvage chemotherapy

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.

Group Type: ACTIVE_COMPARATOR

Cytarabine

Intervention Type: DRUG

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

Mitoxantrone

Intervention Type: DRUG

Once daily IV injection.

Etoposide

Intervention Type: DRUG

Once daily IV injection.

G-CSF

Intervention Type: DRUG

Once daily IV/SC injection.

Fludarabine

Intervention Type: DRUG

Once daily IV injection.

Interventions

Gilteritinib

Tablet administered orally once daily.

Intervention Type: DRUG

Cytarabine

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

Intervention Type: DRUG

Mitoxantrone

Once daily IV injection.

Intervention Type: DRUG

Etoposide

Once daily IV injection.

Intervention Type: DRUG

G-CSF

Once daily IV/SC injection.

Intervention Type: DRUG

Fludarabine

Once daily IV injection.

Intervention Type: DRUG

Other Intervention Names

ASP2215

Eligibility Criteria

Inclusion Criteria

• 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:

1. 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.

• Participant has received study treatment of either LoDAC, MEC or FLAG and has no response or progressive disease.
• Participant have not received other antileukemic therapy after EOT (hydroxyurea is allowed for the control of peripheral leukemic blasts in participants with leukocytosis).
• Participant agrees not to participate in another interventional study while on treatment.

Exclusion Criteria

• 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.
• Participant requires treatment with concomitant drugs that are strong inhibitors or inducers of P-gp with the exception of drugs that are considered absolutely essential for the care of the participant.
• Participant requires treatment with concomitant drugs that target serotonin 5-hydroxytryptamine receptor 1 (5HT1R) or 5-hydroxytryptamine receptor 2B (5HT2BR) receptors or sigma nonspecific receptor with the exception of drugs that are considered absolutely essential for the care of the participant.
• Participant has an active uncontrolled infection.
• Participant is known to have human immunodeficiency virus infection.
• Participant has active hepatitis B or C or other active hepatic disorder.
• Participant has any condition which makes the participant unsuitable for study participation.
• Participant has active clinically significant (graft-versus-host disease) GVHD or is on treatment with systemic corticosteroids for GVHD.
• Participant has an FLT3 mutation other than the following: FLT3-ITD, FLT3-TKD/D835 or FLT3-TKD/I836.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Astellas Pharma Inc

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Astellas Pharma Inc

Locations

Site CN103

Beijing, , China

Site CN108

Beijing, , China

Site CN109

Beijing, , China

Site CN110

Beijing, , China

Site CN131

Beijing, , China

Site CN116

Changchun, , China

Site CN120

Changsha, , China

Site CN119

Fuzhou, , China

Site CN102

Guangzhou, , China

Site CN114

Guangzhou, , China

Site CN121

Guangzhou, , China

Site CN130

Guiyang, , China

Site CN107

Hangzhou, , China

Site CN118

Hefei, , China

Site CN123

Huangpu Qu, , China

Site CN117

Jinan, , China

Site CN133

Lanzhou, , China

Site CN128

Nanjing, , China

Site CN106

Qingdao, , China

Site CN126

Shanghai, , China

Site CN129

Shanghai, , China

Site CN125

Shenyang, , China

Site CN101

Tianjin, , China

Site CN105

Wuhan, , China

Site CN122

Xi'an, , China

Site CN132

Zhangzhou, , China

Site CN113

Zhengzhou, , China

Site CN136

Zhengzhou, , China

Site MY306

Ampang, , Malaysia

Site MY305

George Town, , Malaysia

Site MY301

Johor Bahru, , Malaysia

Site MY304

Kota Kinabalu, , Malaysia

Site MY302

Kuala Lumpur, , Malaysia

Site MY303

Pulau Pinang, , Malaysia

Site RU506

Kemerovo, , Russia

Site RU504

Krasnoyarsk, , Russia

Site RU508

Moscow, , Russia

Site RU509

Moscow, , Russia

Site RU501

Saint Petersburg, , Russia

Site RU502

Saint Petersburg, , Russia

Site RU507

Saint Petersburg, , Russia

Site SG401

Singapore, , Singapore

Site SG402

Singapore, , Singapore

Site SG403

Singapore, , Singapore

Site TH203

Bangkok, , Thailand

Site TH205

Bangkok, , Thailand

Site TH204

Chiang Mai, , Thailand

Site TH201

Khon Kaen, , Thailand

Site TH202

Khon Kaen, , Thailand

Countries

China; Malaysia; Russia; Singapore; Thailand

References

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.

Reference Type: DERIVED

PMID: 40063243 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

CTR20170326

Identifier Type: REGISTRY

Identifier Source: secondary_id

2215-CL-0303

Identifier Type: -

Identifier Source: org_study_id