A Study of ASP2215 (Gilteritinib) by Itself, ASP2215 Combined With Azacitidine or Azacitidine by Itself to Treat Adult Patients Who Have Recently Been Diagnosed With Acute Myeloid Leukemia With a FLT3 Gene Mutation and Who Cannot Receive Standard Chemotherapy

NCT ID: NCT02752035

Last Updated: 2025-09-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 183 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-08-01
• Study Completion Date: 2024-12-18

Brief Summary

This was a clinical study for adult participants who were recently diagnosed with acute myeloid leukemia or AML. AML is a type of cancer. It is when bone marrow makes white blood cells that are not normal. These are called leukemia cells. Some participants with AML have a mutation, or change, in the FLT3 gene. This gene helps leukemia cells make a protein called FLT3. This protein causes the leukemia cells to grow faster.

For participants with AML who could not receive standard chemotherapy, azacitidine (also known as Vidaza®) was a current standard of care treatment option in the United States. This clinical study tested an experimental medicine called ASP2215, also known as gilteritinib. Gilteritinib worked by stopping the leukemia cells from making the FLT3 protein. This helped stop the leukemia cells from growing faster.

This study compared two different treatments. Participants were assigned to one of these two groups by chance: a medicine called azacitidine, also known as Vidaza®, or an experimental medicine gilteritinib in combination with azacitidine. There was a twice as much chance to receive both medicines combined than azacitidine alone. The clinical study may help show which treatment helps patients live longer.

Detailed Description

Participants considered an adult according to local regulation at the time of obtaining informed consent participated in the study.

Safety Cohort Prior to initiation of the randomized trial, 15 participants were enrolled to evaluate the safety and tolerability of ASP2215 given with azacitidine therapy in the study population.

Randomized Trial Approximately 250 participants were randomized in a 2:1 ratio to receive ASP2215 plus azacitidine (Arm AC) or azacitidine only (Arm C). Participants entered the screening period up to 14 days prior to the start of treatment. Participants administered treatment over 28-day cycles.

Earlier protocol versions included a 1:1:1 randomization ratio to receive Arm A: ASP2215, Arm AC: ASP2215 + azacitidine or Arm C: azacitidine. Participants previously randomized to Arm A continued following treatment and assessments as outlined in the protocol.

Conditions

Acute Myeloid Leukemia (AML); Acute Myeloid Leukemia With FMS-like Tyrosine Kinase (FLT3) Mutation

Study Design

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

Study Groups

Safety Cohort: Gilteritinib + Azacitidine (AZA)

Participants received 80 mg (2 tablets of 40 mg) of gilteritinib orally once daily for continuous 28-day cycles and 75 mg/m\^2 of AZA daily via subcutaneous injection or intravenous infusion for 7 days of each 28-day treatment cycle. Depending on the safety cohort data ,the decision to initiate the randomized trial at the targeted dose was made. After the end of treatment period, participants were followed up for 30- day follow up period. Participants were allowed to enter the long-term follow-up period of up to 3 years for collection of subsequent AML treatment, EQ-5D-5L, remission status and survival (cause of death and date of death). Participants in long-term follow-up who were no longer receiving treatment were followed every 3 months for survival until the implementation of the final protocol version 13.0, at which time they were discontinued from the study, as further survival data were no longer needed.

Group Type: EXPERIMENTAL

gilteritinib

Intervention Type: DRUG

Tablet, oral

azacitidine

Intervention Type: DRUG

Subcutaneous injection or intravenous infusion

Randomized Cohort: Gilteritinib + AZA

Participants received 120 mg(3 tablets of 40 mg)of gilteritinib orally once daily for continuous 28-day cycles in combination with 75mg/m\^2 of AZA daily via subcutaneous injection or IV infusion for 7days of each 28-day treatment cycle until the participant no longer received clinical benefit from therapy in the opinion of the investigator,unacceptable toxicity occurred,or the participant met another treatment discontinuation criterion.After the end of treatment period,participants were followed up for 30-day follow up period.Participants were allowed to enter the long-term follow-up period of up to 3 years for collection of subsequent AML treatment,EQ-5D-5L,remission status and survival (cause and date of death).Participants in long-term follow-up who were no longer receiving treatment were followed every 3months for survival until the implementation of the final protocol version 13.0, at which time they were discontinued from the study,as further survival data were no longer needed.

Group Type: EXPERIMENTAL

gilteritinib

Intervention Type: DRUG

Tablet, oral

Randomized Cohort: AZA

Participants received 75 mg/m\^2 of AZA daily via subcutaneous injection or intravenous infusion for 7 days of each 28-day treatment cycle until the participant no longer received clinical benefit from therapy in the opinion of the investigator, unacceptable toxicity occurred or the participant met another treatment discontinuation criterion. After the end of treatment period, participants were followed up for 30- day follow up period. Participants were allowed to enter the long-term follow-up period of up to 3 years for collection of subsequent AML treatment, EQ-5D-5L, remission status and survival (cause of death and date of death). Participants in long-term follow-up who were no longer receiving treatment were followed every 3 months for survival until the implementation of the final protocol version 13.0, at which time they were discontinued from the study, as further survival data were no longer needed.

Group Type: EXPERIMENTAL

gilteritinib

Intervention Type: DRUG

Tablet, oral

azacitidine

Intervention Type: DRUG

Subcutaneous injection or intravenous infusion

Randomized Cohort: Gilteritinib

Participants received 120 mg (3 tablets of 40 mg) of gilteritinib orally once daily for continuous 28-day cycles until the participant no longer received clinical benefit from therapy in the opinion of the investigator, unacceptable toxicity occurred or the participant met another treatment discontinuation criterion. However, randomization to this arm was removed in protocol version 7.0. Participants previously randomized to this arm continued following treatment and assessments as outlined in the protocol.

Group Type: ACTIVE_COMPARATOR

azacitidine

Intervention Type: DRUG

Subcutaneous injection or intravenous infusion

Interventions

gilteritinib

Tablet, oral

Intervention Type: DRUG

azacitidine

Subcutaneous injection or intravenous infusion

Intervention Type: DRUG

Other Intervention Names

ASP2215

Eligibility Criteria

Inclusion Criteria

• Subject is considered an adult according to local regulation at the time of obtaining informed consent.
• Subject has a diagnosis of previously-untreated AML according to World Health Organization (WHO) classification [Swerdlow et al, 2008] as determined by pathology review at the treating institution.
• Subject is positive for FLT3 mutation (internal tandem duplication [ITD] or tyrosine kinase domain [TKD] [D835/I836] mutation) (or for Korea only: ITD alone or ITD with concurrent TKD activating mutation) in bone marrow or whole blood as determined by central laboratory. Note: Only requirement of FLT3 mutation assessment by central laboratory is only applicable to the randomization portion of the study.
• Subject is ineligible for intensive induction chemotherapy by meeting at least 1 of the following criteria:

• Subject is ≥ 65 years of age and ineligible for intensive induction chemotherapy.
• Subject is ≥ 18 to 64 years of age and has any of the following comorbidities: [Ex-US Only]: Congestive heart failure (New York Heart Association {NYHA} class ≤ 3) or ejection fraction (Ef) ≤ 50%; [US Only]: Severe cardiac disorder e.g. congestive heart failure (New York Heart Association [NYHA] class ≤ 3) requiring treatment, ejection fraction ≤ 50%, or chronic stable angina; [Ex-US Only]: Creatinine > 2 mg/dL (177 µmol/L), dialysis or prior renal transplant; [US Only]: Creatinine clearance < 45 mL/min; ECOG performance status ≥ 2;
• [Ex-US Only]: Known pulmonary disease with decreased diffusion capacity of lung for carbon monoxide (DLCO) and/or requiring oxygen ≤ 2 liters per minute; [US Only] Severe pulmonary disorder (e.g., diffusion capacity of lung for carbon monoxide [DLCO] ≤ 65% or forced expiratory volume in the first second [FEV1] ≤ 65%); Prior or current malignancy that does not require concurrent treatment; Subject has received a cumulative anthracycline dose above 400 mg/m2 of doxorubicin (or cumulative maximum dose of another anthracycline). Any other comorbidity incompatible with intensive chemotherapy must be reviewed and approved by the Medical Monitor during screening and before randomization.
• Subject must meet the following criteria as indicated on the clinical laboratory tests:

• Serum AST and ALT ≤ 3.0 x Institutional upper limit of normal (ULN)
• Serum total bilirubin ≤ 1.5 x Institutional ULN
• Serum potassium ≥ Institutional lower limit of normal (LLN)
• Serum magnesium ≥ Institutional LLN Repletion of potassium and magnesium levels during the screening period is allowed.
• Subject is suitable for oral administration of study drug.
• Female subject is eligible to participate if female subject is not pregnant and at least one of the following conditions applies:

• Not a woman of childbearing potential (WOCBP); OR
• WOCBP agrees to follow the contraceptive guidance starting at screening and continue throughout the study period, and for at least 180 days after the final study drug administration.
• Female subject must agree not to breastfeed starting at screening and throughout the study period, and for 60 days after the final study drug administration.
• Female subject must not donate ova starting at screening and throughout the study period, and for 180 days after the final study drug administration.
• Male subject with female partners of childbearing potential must agree to use contraception as detailed in Contraception Requirements, starting at screening and continue throughout the study period, and for 120 days after the final study drug administration.
• Male subject must not donate sperm starting at screening and throughout the study period and for 120 days after the final study drug administration.
• Subject agrees not to participate in another interventional study while on treatment.

Exclusion Criteria

• Subject was diagnosed as acute promyelocytic leukemia (APL).
• Subject has BCR-ABL-positive leukemia (chronic myelogenous leukemia in blast crisis).
• Subject has received previous therapy for AML, with the exception of the following:

• Emergency leukapheresis
• Hydroxyurea
• Preemptive treatment with retinoic acid prior to exclusion of APL ≤ 7 days
• Growth factor or cytokine support
• Steroids
• Subject has clinically active central nervous system leukemia.
• Subject has been diagnosed with another malignancy that requires concurrent treatment (with the exception of hormone therapy limited to those therapies that prevent recurrence and/or spread of cancer) or hepatic malignancy regardless of need for treatment.
• Subject requires treatment with concomitant drugs that are strong inducers of cytochrome P450 CYP3A/P-glycoprotein (P-gp).
• Subject 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 subject.
• Subject requires treatment with concomitant drugs that target serotonin 5-hydroxytryptamine receptor 2B (5HT2BR) or sigma nonspecific receptor with the exception of drugs that are considered absolutely essential for the care of the subject.
• Subject has congestive heart failure classified as New York Heart Association Class IV.
• Subject with mean Fridericia-corrected QT interval (QTcF) > 480 ms at screening based on central reading.
• Subject with a history of Long QT Syndrome at screening.
• [Ex-US Only]: Subject has known pulmonary function tests with diffusion capacity of lung for carbon monoxide (DLCO) ≤ 50%, forced expiratory volume in the first second (FEV1) ≤ 60%, dyspnea at rest or requiring oxygen or any pleural neoplasm (Transient use of supplemental oxygen is allowed.)
• Subject has active hepatitis B or C or other active hepatic disorder.

• Subjects with positive hepatitis B surface antigen (HBsAg) or detectable hepatitis B DNA are not eligible.
• Subjects with negative HBsAg, positive hepatitis B core antibody and negative hepatitis B surface antibody will be eligible if hepatitis B DNA is undetectable.
• Subjects with antibodies to hepatitis C virus will be eligible if hepatitis C RNA is undetectable
• Subject has any condition which makes the subject unsuitable for study participation, including any contraindications of azacitidine.
• Subject has a known or suspected hypersensitivity to ASP2215, azacitidine or any components of the formulations used.
• [US Only]: Subject is ≥ 65 to 74 years of age, suitable for and willing to receive intensive induction chemotherapy.

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

Sponsors

Astellas Pharma Global Development, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Astellas Pharma Global Development, Inc.

Locations

UCLA David Geffen School of Medicine

Los Angeles, California, United States

University of California, Irvine Medical Center

Orange, California, United States

Robert H. Lurie Comprehensive Cancer Center

Chicago, Illinois, United States

Rush University Medical Center

Chicago, Illinois, United States

St. Louis University Cancer Center - Hematology/Oncology

St Louis, Missouri, United States

Hackensack University Medical Center - John Theurer Cancer Center

Hackensack, New Jersey, United States

Hematology-Oncology Associates of Northern NJ

Morristown, New Jersey, United States

Roswell Park Cancer Institute

Buffalo, New York, United States

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Weill Cornell Medical College-New York Presbyterian Hospital

New York, New York, United States

GHS Cancer Institute

Greenville, South Carolina, United States

LDS Hospital

Salt Lake City, Utah, United States

Site AU61004

Liverpool, New South Wales, Australia

Site AU61008

Adelaide, South Australia, Australia

Site AU61007

Geelong, Victoria, Australia

Site BE32007

Brussels, Brussels Capital, Belgium

Site BE32003

Brussels, Bruxelles-Capitale, Region de, Belgium

Site BE32006

Ghent, , Belgium

Site CA15009

Edmonton, Alberta, Canada

Site CA15011

Toronto, Ontario, Canada

Site CA15002

Toronto, Ontario, Canada

Site CA15006

Montreal, Quebec, Canada

Site FR33003

Nîmes, Gard, France

Site FR33002

Pessac, Gironde, France

Site FR33015

Rouen, Haute-Normandie, France

Site FR33019

Montpellier, Herault, France

Site FR33018

Rennes, Ille-et-Vilaine, France

Site FR33001

Nantes, Loire-Atlantique, France

Site FR33023

Valenciennes, Nord, France

Site FR33013

Pierre-Bénite, Rhone, France

Site FR33017

Le Mans, Sarthe, France

Site FR33012

Poitiers, Vienne, France

Site FR33009

Angers, , France

Site FR33020

Bayonne, , France

Site FR33004

Lille, , France

Site FR33006

Lille, , France

Site DE49002

Tübingen, Baden-Wurttemberg, Germany

Site DE49007

München, Bavaria, Germany

Site DE49005

Frankfurt am Main, Hesse, Germany

Site DE49012

Braunschweig, Lower Saxony, Germany

Site DE49004

Hanover, Lower Saxony, Germany

Site DE49015

Rostock, Mecklenburg-Vorpommern, Germany

Site DE49009

Halle, Saxony-Anhalt, Germany

Site DE49003

Berlin, , Germany

Site DE49011

Stuttgart, , Germany

Site IT39009

Ancona, , Italy

Site IT39015

Bologna, , Italy

Site IT39012

Florence, , Italy

Site IT39004

Milan, , Italy

Site IT39007

Monza, , Italy

Site IT39001

Napoli, , Italy

Site IT39014

Novara, , Italy

Site IT39006

Palermo, , Italy

Site IT39005

Pavia, , Italy

Site IT39011

San Giovanni Rotondo, , Italy

Site JP81018

Anjo, Aichi-ken, Japan

Site JP81007

Nagoya, Aichi-ken, Japan

Site JP81027

Matsuyama, Ehime, Japan

Site JP81021

Fukuyama, Hiroshima, Japan

Site JP81031

Sapporo, Hokkaido, Japan

Site JP81033

Sapporo, Hokkaido, Japan

Site JP81015

Kobe, Hyōgo, Japan

Site JP81034

Hitachi, Ibaraki, Japan

Site JP81023

Kanazawa, Ishikawa-ken, Japan

Site JP81001

Isehara, Kanagawa, Japan

Site JP81032

Yokohama, Kanagawa, Japan

Site JP81012

Sendai, Miyagi, Japan

Site JP81011

Kurashiki, Okayama-ken, Japan

Site JP81029

Shibuya-ku, Tokyo, Japan

Site JP81014

Shinagawa-ku, Tokyo, Japan

Site JP81035

Chiba, , Japan

Site JP81008

Fukuoka, , Japan

Site JP81024

Gifu, , Japan

Site JP81005

Kumamoto, , Japan

Site JP81016

Kyoto, , Japan

Site JP81004

Nagasaki, , Japan

Site JP81017

Nagasaki, , Japan

Site JP81030

Osaka, , Japan

Site JP81036

Osaka, , Japan

Site JP81026

Tokushima, , Japan

Site JP81019

Toyama, , Japan

Site PL48003

Lublin, Lublin Voivodeship, Poland

Site PL48004

Warsaw, Masovian Voivodeship, Poland

Site PL48002

Opole, Opole Voivodeship, Poland

Site PL48001

Olsztyn, Warmian-Masurian Voivodeship, Poland

Site KR82003

Namdong, Incheon Gwang'yeogsiv, South Korea

Site KR82013

Seoul, Seoul Teugbyeolsi, South Korea

Site KR82006

Seoul, Seoul Teugbyeolsi, South Korea

Site KR82002

Seoul, Seoul Teugbyeolsi, South Korea

Site KR82001

Ulsan, Ulsan Gwang'yeogsi, South Korea

Site KR82014

Busan, , South Korea

Site KR82010

Hwasun-gun, , South Korea

Site KR82015

Seongnam-si, , South Korea

Site KR82012

Seoul, , South Korea

Site ES34007

Palma de Mallorca, Balearic Islands, Spain

Site ES34003

Oviedo, Principality of Asturias, Spain

Site ES34008

Barcelona, , Spain

Site ES34004

Barcelona, , Spain

Site ES34010

Barcelona, , Spain

Site ES34009

Barcelona, , Spain

Site ES34002

Cáceres, , Spain

Site ES34013

Madrid, , Spain

Site ES34005

Valencia, , Spain

Site TW88604

Kaohsiung City, , Taiwan

Site TW88605

Kwei Shan Hsiang, , Taiwan

Site TW88602

Tainan City, , Taiwan

Site TW88609

Tainan City, , Taiwan

Site TW88601

Taipei, , Taiwan

Site TW88608

Taipei, , Taiwan

Site TW88610

Taipei, , Taiwan

Site GB44007

Sheffield, , United Kingdom

Countries

United States; Australia; Belgium; Canada; France; Germany; Italy; Japan; Poland; South Korea; Spain; Taiwan; United Kingdom

References

Wang ES, Montesinos P, Minden MD, Lee JH, Heuser M, Naoe T, Chou WC, Laribi K, Esteve J, Altman JK, Havelange V, Watson AM, Gambacorti-Passerini C, Patkowska E, Liu S, Wu R, Philipose N, Hill JE, Gill SC, Rich ES, Tiu RV. Phase 3 trial of gilteritinib plus azacitidine vs azacitidine for newly diagnosed FLT3mut+ AML ineligible for intensive chemotherapy. Blood. 2022 Oct 27;140(17):1845-1857. doi: 10.1182/blood.2021014586.

Reference Type: DERIVED

PMID: 35917453 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2015-001790-41

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2215-CL-0201

Identifier Type: -

Identifier Source: org_study_id