A Study of ASP2215 in Combination With Induction and Consolidation Chemotherapy in Patients With Newly Diagnosed Acute Myeloid Leukemia.

NCT ID: NCT02310321

Last Updated: 2025-09-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 97 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-02-26
• Study Completion Date: 2024-07-09

Brief Summary

The purpose of phase 1 part in this study was to determine the maximum tolerated dose (MTD) and/or recommended expansion dose (RED) of ASP2215 concomitant with cytarabine/idarubicin as induction chemotherapy based on the status of the onset of dose-limiting toxicity (DLT) in newly diagnosed Acute Myeloid Leukemia (AML) subjects. Phase 1 part also evaluated safety and tolerability and characterized the pharmacokinetic (PK) parameters of ASP2215 concomitant with induction and consolidation chemotherapy as well as evaluated the PK parameters of cytarabine concomitant with ASP2215.

The purpose of phase 2 part was to evaluate efficacy of ASP2215 in combination with induction therapy. Phase 2 cohort also evaluated safety and characterized the PK parameters of ASP2215 in combination with induction and consolidation therapy followed by maintenance therapy in newly diagnosed FLT3-mutated AML subjects.

Detailed Description

This study was composed of Phase 1 part (the dose-evaluation part and the expansion part) and Phase 2 part.

In the dose-evaluation part of Phase 1 part, at least 3 subjects received ASP2215 at each dose (low, middle, and high) for determination of MTD and/or RED. Treatment of AML in Phase 1 part was composed of 3 periods of therapy: remission induction, consolidation, and maintenance. The decision of whether or not to proceed to the next dose was made based on the occurrence of DLT during Cycle 1 of the induction period.

In the expansion part of Phase 1 part, a maximum of 3 subjects received ASP2215 at RED that had been recommended in the dose-evaluation part and the safety was assessed based on the onset of DLTs during Cycle 1 of the induction and consolidation periods.

In Phase 2 part, Subjects received ASP2215 at the recommended dose established in Phase 1 part. The target population was limited to newly diagnosed FLT3-mutated AML.

Conditions

Acute Myeloid Leukemia; FLT3-mutated Acute Myeloid Leukemia

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Phase 1: Dose Evaluation (DEv)

Induction period: Participants received 120 milligrams (mg) gilteritinib (3 tablets of 40 mg) orally, once daily from day 4 to 17 combined with chemotherapy (idarubicin: 12 mg per square meters per day [mg/m^2/day] on days 1 to 3, cytarabine: 100 mg/m^2/day on days 1 to 7) via intravenous (IV) infusion; in cycles (C) 1 and 2 (1 cycle= 42 days).

Consolidation period: Participants received 120 mg gilteritinib (3 tablets of 40 mg) orally, once daily from day 1 to 14 combined with chemotherapy (cytarabine: 1500 mg/m^2, twice daily on days 1, 3, and 5) via IV infusion; in the consolidation period in C1 to 3 (1 cycle= 28 days).

Duration of infusion was determined by site clinical practice and local package insert in both induction and consolidation periods..

Maintenance period: Participants received 120 mg gilteritinib (3 tablets of 40 mg) orally, once daily from days 1 to 28 in the maintenance period in C1 to 26 or untill discontinuation criterion is met (1 cycle= 28 days).

Group Type: EXPERIMENTAL

Gilteritinib

Intervention Type: DRUG

Once-daily oral administration on 14 consecutive days in every cycle in each period.

Idarubicin

Intervention Type: DRUG

Induction period: Once-daily intravenous injection of 12 mg/m\^2 idarubicin on 3 consecutive days.

Cytarabine

Intervention Type: DRUG

Induction period: Once-daily intravenous injection of 100 mg/m^2 cytarabine on 7 consecutive days.

Consolidation period: Twice-daily intravenous injection of 1.5 g/m^2 cytarabine on Days 1, 3, and 5.

Phase 1: Dose Expansion (DEx)

Induction period: Participants received 120 mg gilteritinib (3 tablets of 40 mg) orally, once a day from days 4 to 17 in combination with chemotherapy (idarubicin: 12 mg/m^2/day on days 1 to 3, cytarabine: 100 mg/m^2/day on days 1 to 7) via IV infusion; in the induction period in C1 and 2 (1 cycle= 42 days).

Consolidation period: Participants received 120 mg gilteritinib (3 tablets of 40 mg) orally, once a day from days 1 to 14 in combination with chemotherapy (cytarabine: 1500 mg/m^2, twice daily on days 1, 3, and 5) via IV infusion; in the consolidation period in C1 to 3 (1 cycle= 28 days).

Duration of infusion was determined based on site clinical practice and the local package insert in both induction and consolidation periods.

Maintenance period: Participants received 120 mg gilteritinib (3 tablets of 40 mg) orally, once a day from days 1 to 28 in the maintenance period in C1 to 26 or a discontinuation criterion is met (1 cycle= 28 days).

Group Type: EXPERIMENTAL

Gilteritinib

Intervention Type: DRUG

Once-daily oral administration on 14 consecutive days in every cycle in each period.

Idarubicin

Intervention Type: DRUG

Induction period: Once-daily intravenous injection of 12 mg/m\^2 idarubicin on 3 consecutive days.

Cytarabine

Intervention Type: DRUG

Induction period: Once-daily intravenous injection of 100 mg/m^2 cytarabine on 7 consecutive days.

Consolidation period: Twice-daily intravenous injection of 1.5 g/m^2 cytarabine on Days 1, 3, and 5.

Phase 2: FLT3-mutated AML

Induction period: Participants received 120 mg gilteritinib (3 tablets of 40 mg) orally, once daily from days 8 until blood recovery combined with chemotherapy (idarubicin: 12 mg/m^2/day on days 1 to 3, cytarabine: 100 mg/m^2/day on days 1 to 7) via IV infusion; in C1 and 2. Each cycle was extended until blood recovery was observed.

Consolidation period: Participants received 120 mg gilteritinib (3 tablets of 40 mg) orally, once daily from days 1 until blood recovery combined with chemotherapy (cytarabine: 1500 mg/m^2, twice daily on days 1, 3, and 5) via IV infusion; in C1 to 3. Each cycle was extended until blood recovery was observed.

Duration of infusion was based on site clinical practice and the local package insert in both induction and consolidation periods.

Maintenance period: Participants received 120 mg gilteritinib (3 tablets of 40 mg) orally, once daily from days 1 to 28 in the maintenance period in C1 to 26 or a discontinuation criterion is met (1 cycle= 28 days).

Group Type: EXPERIMENTAL

Gilteritinib

Intervention Type: DRUG

Once-daily oral administration on 14 consecutive days in every cycle in each period.

Idarubicin

Intervention Type: DRUG

Induction period: Once-daily intravenous injection of 12 mg/m\^2 idarubicin on 3 consecutive days.

Cytarabine

Intervention Type: DRUG

Induction period: Once-daily intravenous injection of 100 mg/m^2 cytarabine on 7 consecutive days.

Consolidation period: Twice-daily intravenous injection of 1.5 g/m^2 cytarabine on Days 1, 3, and 5.

Interventions

Gilteritinib

Once-daily oral administration on 14 consecutive days in every cycle in each period.

Intervention Type: DRUG

Idarubicin

Induction period: Once-daily intravenous injection of 12 mg/m\^2 idarubicin on 3 consecutive days.

Intervention Type: DRUG

Cytarabine

Induction period: Once-daily intravenous injection of 100 mg/m^2 cytarabine on 7 consecutive days.

Consolidation period: Twice-daily intravenous injection of 1.5 g/m^2 cytarabine on Days 1, 3, and 5.

Intervention Type: DRUG

Other Intervention Names

Xospata; ASP2215

Eligibility Criteria

Inclusion Criteria

[Phase 1 part]

• Subject is defined as having previously untreated de novo AML according to the World Health Organization (WHO) criteria (2008) within 28 days prior to study enrollment.
• Subject has an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.
• Subject must meet all of the following criteria in the laboratory test at screening:

• Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels of ≤ 2.5 × institutional upper limit of normal (ULN)
• Total serum bilirubin level of ≤ 1.5 × institutional ULN
• Serum creatinine level of ≤ 1.5 × institutional ULN or an estimated glomerular filtration rate (eGFR) of > 50 mL/min
• Subject is suitable for oral administration of ASP2215.
• Female subject falls under the following:

• Of non-childbearing potential:
• ・Post-menopausal (defined as at least 1 year with no menses without a medical reason such as drug administration) at screening, or
• ・Documented surgically sterile or status post-hysterectomy (at least 1 month prior to screening)
• Of childbearing potential:
• ・Has a negative result for the pregnancy test at screening, and
• ・Agrees to use an appropriate contraception starting at screening and throughout the study period and for 60 days after the final study drug administration
• Female subject agrees not to breastfeed starting at screening and throughout the study period and for 60 days after the final study drug administration.
• Female subject agrees not to donate ova starting at screening and throughout the study period and for 60 days after the final study drug administration.
• Male subject and his female spouse/partner who is of childbearing potential agrees to use an appropriate contraception starting at screening and throughout the study period and for 120 days after the final study drug administration.
• Male subject agrees not to 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 study treatment.
• Subject can be admitted during the induction period.

[Phase 2 part]

• Subject has a diagnosis of previously-untreated de novo acute myeloid leukemia (AML) according to World Health Organization (WHO) classification (2017) documented within 28 days prior to enrollment.
• Subject is positive for FLT3-ITD and/or TKD mutation in bone marrow or whole blood as determined by the central lab. Registration by the local lab result is not acceptable.
• Subject has an ECOG performance status (PS) 0 to 1. Subject who has an ECOG PS 2 is eligible only if the primary disease related symptoms such as pneumonia and febrile neutropenia are the cause of PS score.
• Subject is suitable for oral administration of ASP2215.
• Female subject is not pregnant and at least 1 of the following conditions apply:

• Not a woman of childbearing potential (WOCBP)
• WOCBP who agrees to follow the contraceptive guidance from the time of informed consent through at least 180 days after final study treatment 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 and their female partners who are of childbearing potential must be using highly effective contraception per locally accepted standards in addition to a barrier method 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.
• Male subject with pregnant partner(s) must agree to remain abstinent or use a condom for the duration of the pregnancy throughout the study period and for 120 days after the final study treatment administration.
• Subject agrees not to participate in another interventional study while on treatment.
• Subject must meet the following criteria as indicated on the clinical laboratory tests:

• Serum creatinine ≤ 1.5 × institutional upper limit of normal (ULN), or if serum creatinine outside normal range, then glomerular filtration rate (GFR) > 50 mL/min/1.73m^2 as calculated with the 4-parameter Modification of Diet in Renal Disease (MDRD) equation.
• Serum total bilirubin ≤ 2.5 mg/dL (43 μmol/L), except for subjects with Gilbert's syndrome.
• Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 x ULN. If liver abnormality by the primary disease is suspected, subject may be pre-registered to initiate the chemotherapy. Prior to registration, AST/ALT values must meet the criteria to continue the study.
• Serum magnesium ≥ institutional lower limit of normal (LLN). Subject may pre-register without magnesium value, but subject must meet the criteria prior to the full registration on Day 8.
• Serum potassium ≥ institutional lower limit of normal (LLN).

Exclusion Criteria

[Phase 1 part]

• Subject was diagnosed with acute promyelocytic leukemia (APL).
• Subject has breakpoint cluster region-abelson (BCR-ABL)-positive leukemia (chronic myelogenous leukemia in blast crisis).
• Subject has active malignant tumors other than AML or myelodysplastic syndrome (MDS).
• Subject has received prior AML treatment except for the following:

• Urgent leukapheresis
• Hydroxyurea administration for emergency treatment of hyperleukocytosis (≤ 7 days)
• Administration of retinoic acid before the diagnosis to exclude APL (≤ 7 days)
• Supportive care using growth factors or cytokines
• Steroid administration to treat hypersensitivity or blood transfusion reactions
• Subject has clinically active central nervous system leukemia.
• Subject has disseminated intravascular coagulation (DIC).
• Subject has had major surgery within 28 days prior to the first study drug administration.
• Subject has had radiation therapy within 28 days prior to the first study drug administration.
• Subject has congestive heart failure of New York Heart Association (NYHA) class 3 or 4, or subject with a past history of congestive heart failure of NYHA class 3 or 4 and in whom echocardiogram (ECHO) or Multiple Gate Acquisition (MUGA) scan performed within 3 months prior to screening or at screening showed a left ventricular ejection fraction (LVEF) of < 45%.
• Subject has cardiac impairment or a clinically significant cardiac disease, including any one of the following:

• Complete left bundle branch block
• Obligate use of a cardiac pacemaker
• Long QT syndrome at Screening
• Prolongation of the QTc interval (> 450 ms) on electrocardiogram (ECG) at screening
• Right bundle branch block + left anterior hemiblock (bifascicular block)
• Angina pectoris within 3 months prior to study drug administration
• Acute myocardial infarction within 3 months prior to study drug administration
• Subject requires treatment with concomitant drugs that are strong inducers of cytochrome P450 (CYP)3A.
• Subject requires treatment with concomitant drugs that are strong inhibitors or inducers of P glycoprotein (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 5HT1 or 5HT2B receptors or sigma receptors, with the exception of drugs that are considered absolutely essential for treatment of the subject.
• Subject has an active uncontrollable infection.
• Subject is known to have human immunodeficiency virus (HIV) infection.
• Subject has active hepatitis B or C or other active hepatic disorders.
• Subject has any condition that, in the investigator's or sub-investigator's opinion, makes the subject unsuitable for study participation.
• Potassium and magnesium levels of below institutional lower limit of normal in the laboratory test at screening.

[Phase 2 part]

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

• Emergency leukapheresis
• Emergency treatment for hyperleukocytosis with hydroxyurea for ≤ 10 days
• Preemptive treatment with retinoic acid prior to exclusion of APL ≤ 7 days
• Growth factor or cytokine support
• Steroids for the treatment of hypersensitivity or transfusion reactions.
• Subject has QTcF interval > 450 ms (average of triplicate determinations based on central reading).
• Subject with long QT syndrome.
• Subject has clinically active central nervous system leukemia.
• Subject has had major surgery within 4 weeks prior to the first study dose.
• Subject has radiation therapy within 4 weeks prior to the first study dose.
• Subject has immediate life-threatening, severe complications of leukemia such as severe uncontrolled bleeding and/or severe disseminated intravascular coagulation
• Subject is known to have human immunodeficiency virus infection.
• Subject has active hepatitis B or C.
• Subject has an uncontrolled infection. An infection controlled with an approved or closely monitored antibiotic/antiviral/antifungal treatment is allowed.
• Subject has uncontrolled angina, severe uncontrolled ventricular arrhythmias, electrocardiographic evidence of acute ischemia, congestive heart failure New York Heart Association (NYHA) class 3 or 4 or subject has a history of congestive heart failure of NYHA class 3 or 4 and echocardiogram (ECHO) or Multiple Gate Acquisition (MUGA) scan performed within 3 months prior to screening or at screening showed a left ventricular ejection fraction (LVEF) of < 45%.
• Subject requires treatment with concomitant drugs that are strong inducers of cytochrome P450 (CYP) 3A.
• Subject requires treatment with concomitant drugs that target serotonin 5HT2B receptors or sigma nonspecific receptors, with the exception of drugs that are considered absolutely essential for treatment of the subject.
• Subject requires treatment with concomitant drugs that are strong inhibitors or inducers of P glycoprotein (P-gp) with the exception of drugs that are considered absolutely essential for the care of the subject.
• Subject has prior malignancies, except resected basal cell carcinoma or treated cervical carcinoma in situ. Cancer treated with curative intent ≥ 5 years previously will be allowed. Cancer treated with curative intent < 5 years previously will not be allowed.
• Subject has any condition which makes the subject unsuitable for study participation.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 69 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 JP81037

Anjo, Aichi-ken, Japan

Site JP00003

Nagoya, Aichi-ken, Japan

Site JP81003

Nagoya, Aichi-ken, Japan

Site JP81027

Nagoya, Aichi-ken, Japan

Site JP81038

Toyohashi, Aichi-ken, Japan

Site JP81010

Narita, Chiba, Japan

Site JP81039

Matsuyama, Ehime, Japan

Site JP81007

Yoshida-gun, Fukui, Japan

Site JP00002

Maebashi, Gunma, Japan

Site JP81001

Maebashi, Gunma, Japan

Site JP81026

Fukuyama, Hiroshima, Japan

Site JP81018

Ōtake, Hiroshima, Japan

Site JP81014

Sapporo, Hokkaido, Japan

Site JP81015

Sapporo, Hokkaido, Japan

Site JP81043

Himeji, Hyōgo, Japan

Site JP00007

Kobe, Hyōgo, Japan

Site JP81006

Kobe, Hyōgo, Japan

Site JP81036

Mito, Ibaraki, Japan

Site JP81023

Tsukuba, Ibaraki, Japan

Site JP81020

Kanazawa, Ishikawa-ken, Japan

Site JP81013

Isehara, Kanagawa, Japan

Site JP00006

Yokohama, Kanagawa, Japan

Site JP81005

Yokohama, Kanagawa, Japan

Site JP81024

Yokohama, Kanagawa, Japan

Site JP81035

Sendai, Miyagi, Japan

SIte JP81011

Ōmura, Nagasaki, Japan

Site JP81041

Tenri, Nara, Japan

Site JP81022

Shimono, Tochigi, Japan

Site JP81040

Bunkyo-ku, Tokyo, Japan

Site JP00005

Shinagawa-ku, Tokyo, Japan

Site JP81032

Shinagawa-ku, Tokyo, Japan

Site JP81029

Akita, , Japan

Site JP81008

Chiba, , Japan

Site JP00001

Fukuoka, , Japan

Site JP81004

Fukuoka, , Japan

Site JP81025

Fukuoka, , Japan

Site JP81031

Fukushima, , Japan

Site JP81030

Gifu, , Japan

Site JP81033

Kochi, , Japan

Site JP81028

Kumamoto, , Japan

Site JP81016

Kyoto, , Japan

Site JP81012

Nagasaki, , Japan

Site JP81009

Okayama, , Japan

Site JP81019

Osaka, , Japan

Site JP81021

Osaka, , Japan

Site KR82005

Busan, , South Korea

Site KR82002

Incheon, , South Korea

Site KR82001

Seoul, , South Korea

Site KR82003

Seoul, , South Korea

Site KR82004

Seoul, , South Korea

Site KR82006

Seoul, , South Korea

Site TW88604

Kaohsiung City, , Taiwan

Site TW88602

Taichung, , Taiwan

Site TW88601

Tainan City, , Taiwan

Site TW88603

Taoyuan District, , Taiwan

Countries

Japan; South Korea; Taiwan

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2215-CL-0104

Identifier Type: -

Identifier Source: org_study_id