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Acute Myeloid LeukemiaPhase 1/2NCT02310321

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

A Phase 1/2 study testing Gilteritinib, Idarubicin and Cytarabine in people with Acute Myeloid Leukemia and FLT3-mutated Acute Myeloid Leukemia, run by Astellas Pharma Inc at 55 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 to 69 years
What is being tested?
Gilteritinib, Idarubicin and Cytarabine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
97 participants
Where
55 sitesin 3 countries
Study dates
26 Feb 2015to 9 Jul 2024
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 69 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • [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
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  • 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).

Who cannot join

  • [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
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  • 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.

Trial locations and contacts

55 sites in 3 countries.

55 sites in 3 countries

Japan45 sites

  • Site JP81029

    Akita

  • Site JP81037

    Anjo, Aichi-ken

  • Site JP81040

    Bunkyo-ku, Tokyo

  • Site JP81008

    Chiba

  • Site JP00001

    Fukuoka

  • Site JP81004

    Fukuoka

  • Site JP81025

    Fukuoka

  • Site JP81031

    Fukushima

  • Site JP81026

    Fukuyama, Hiroshima

  • Site JP81030

    Gifu

  • Site JP81043

    Himeji, Hyōgo

  • Site JP81013

    Isehara, Kanagawa

  • Site JP81020

    Kanazawa, Ishikawa-ken

  • Site JP00007

    Kobe, Hyōgo

  • Site JP81006

    Kobe, Hyōgo

  • Site JP81033

    Kochi

  • Site JP81028

    Kumamoto

  • Site JP81016

    Kyoto

  • Site JP00002

    Maebashi, Gunma

  • Site JP81001

    Maebashi, Gunma

  • Site JP81039

    Matsuyama, Ehime

  • Site JP81036

    Mito, Ibaraki

  • Site JP81012

    Nagasaki

  • Site JP00003

    Nagoya, Aichi-ken

  • Site JP81003

    Nagoya, Aichi-ken

  • Site JP81027

    Nagoya, Aichi-ken

  • Site JP81010

    Narita, Chiba

  • Site JP81009

    Okayama

  • SIte JP81011

    Ōmura, Nagasaki

  • Site JP81019

    Osaka

  • Site JP81021

    Osaka

  • Site JP81018

    Ōtake, Hiroshima

  • Site JP81014

    Sapporo, Hokkaido

  • Site JP81015

    Sapporo, Hokkaido

  • Site JP81035

    Sendai, Miyagi

  • Site JP81022

    Shimono, Tochigi

  • Site JP00005

    Shinagawa-ku, Tokyo

  • Site JP81032

    Shinagawa-ku, Tokyo

  • Site JP81041

    Tenri, Nara

  • Site JP81038

    Toyohashi, Aichi-ken

  • Site JP81023

    Tsukuba, Ibaraki

  • Site JP00006

    Yokohama, Kanagawa

  • Site JP81005

    Yokohama, Kanagawa

  • Site JP81024

    Yokohama, Kanagawa

  • Site JP81007

    Yoshida-gun, Fukui

Other trials in Japan

South Korea6 sites

  • Site KR82005

    Busan

  • Site KR82002

    Incheon

  • Site KR82001

    Seoul

  • Site KR82003

    Seoul

  • Site KR82004

    Seoul

  • Site KR82006

    Seoul

Other trials in South Korea

Taiwan4 sites

  • Site TW88604

    Kaohsiung City

  • Site TW88602

    Taichung

  • Site TW88601

    Tainan

  • Site TW88603

    Taoyuan

Other trials in Taiwan

About this study

Official title: A Phase 1/2 Study of ASP2215 in Combination With Induction and Consolidation Chemotherapy in Patients With Newly Diagnosed Acute Myeloid Leukemia

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.

Read the 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.

Being tested
Gilteritinib, Idarubicin, Cytarabine
Keywords
Acute Myeloid Leukemia, Cytarabine, Idarubicin, ASP2215
Medical subject headings
Leukemia, Myeloid, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • GilteritinibDrug

    Also called Xospata, ASP2215

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

  • IdarubicinDrug

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

  • CytarabineDrug

    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.

Study groups in NCT02310321
Study groupRoleWhat they receive
Phase 1: Dose Evaluation (DEv)ExperimentalInduction 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).
Receives: Drug: Gilteritinib; Drug: Idarubicin; Drug: Cytarabine
Phase 1: Dose Expansion (DEx)ExperimentalInduction 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).
Receives: Drug: Gilteritinib; Drug: Idarubicin; Drug: Cytarabine
Phase 2: FLT3-mutated AMLExperimentalInduction 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).
Receives: Drug: Gilteritinib; Drug: Idarubicin; Drug: Cytarabine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Phase 1 Part: Maximum Tolerated Dose (MTD) of Gilteritinib

    The MTD was defined as the highest dose of gilteritinib at which the posterior mean of the DLT incidence during Cycle 1 of induction therapy was estimated to be closest to 33%.

    Measured: Day 1 up to the end of Induction period cycle 1 (up to 42 days)

  2. Phase 1 Part: Recommended Expansion Dose (RED) of Gilteritinib

    RED was the recommended dose used in Phase 2 of the study that was decided by the sponsor's responsible person by comprehensively assessing the data obtained from the study.

    Measured: Day 1 up to the end of Induction period cycle 1 (up to 42 days)

  3. Phase 1 Part: Number of Participants With Dose Limiting Toxicities (DLTs) of Gilteritinib

    DLTs were defined as:

    Any Grade ≥ 3 non-hematologic or extramedullary toxicity with the following exceptions:

    • Anorexia or fatigue
    • Grade 3 nausea and/or vomiting if participant did not require tube feeding or total parenteral nutrition, or diarrhea if the events did not require or prolong hospitalization that could be managed to grade ≤ 2 with standard antiemetic or antidiarrheal medications used at prescribed dose within 7 days of onset.
    • Grade 3 mucositis that resolved to Grade ≤ 2 within 7 days of onset, fever with neutropenia, with or without infection, infection
    • Grade 4 peripheral neutrophil count < 500/cubic millimeters (mm^3)
    • Platelet count < 20,000/mm^3 due to bone marrow hypoplasia
    • Grade ≥ 3 platelet count < 50,000/mm^3 accompanying bleeding
    • Grade 4 platelet count < 25,000/mm^3 requiring platelet transfusion

    DLT was assessed until cycle 1 of dose evaluation induction period and until cycle 1 of dose expansion consolidation period.

    Measured: Day 1 up to the end of Consolidation Cycle 1 (approximately up to 4 months)

  4. Phase 1 Part: Number of Participants With Treatment Emergent Adverse Events (TEAEs)

    An AE was defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE could therefore be any unfavorable \& unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. TEAE included both serious and non-serious AEs. TEAE for Phase 1 was defined as an AE observed after the date of first dose until 30 days after the last dose.

    Measured: From the date of first dose up to 30 days after the last dose ( maximum duration up to approximately 4.1 years)

  5. Phase 2 Part: Complete Remission (CR) Rate: Induction Period

    Percentage of participants with CR was reported. CR was defined as a morphologically leukemia-free state at the post-baseline visit, having a neutrophil count of ≥ 1,000/mm3 and platelet count of ≥ 100,000/mm3, bone marrow blasts < 5%. No evidence of Auer rods and no evidence of extramedullary leukemia. The blast counts in peripheral blood was ≤ 2%.

    Measured: From the date of first dose up to the start of Consolidation (approximately up to 4 months)

Secondary outcomes (21)

  1. Phase 1 Part: Maximum Concentration (Cmax) of Gilteritinib Concomitant With Induction and Consolidation Chemotherapy

    Cmax was derived from the PK samples collected. It was planned that standard deviation(SD) would only be calculated if there are more than 3 participants analyzed otherwise, SD was not calculated.

    Measured: Induction period: Pre-dose, 1, 2, 4, 6, 10, and 24 hours post-dose on Cycle 1 Day 4 Consolidation period: Pre-dose, 1, 2, 4, 6, 10, and 24 hours post-dose on Cycle 1 Day 1

  2. Phase 1 Part: Time to Attain Cmax (Tmax) of Gilteritinib Concomitant With Induction and Consolidation Chemotherapy

    Tmax was derived from the PK samples collected.

    Measured: Induction period: Pre-dose, 1, 2, 4, 6, 10, and 24 hours post-dose on Cycle 1 Day 4 Consolidation period: Pre-dose, 1, 2, 4, 6, 10, and 24 hours post-dose on Cycle 1 Day 1

  3. Phase 1 Part: Area Under Plasma Concentration-time Curve From Time 0 to 24 (AUC24) of Gilteritinib Concomitant With Induction and Consolidation Chemotherapy

    AUC24 was derived from the PK samples collected. It was planned that standard deviation(SD) would only be calculated if there are more than 3 participants analyzed otherwise, SD was not calculated.

    Measured: Induction period: Pre-dose, 1, 2, 4, 6, 10, and 24 hours post-dose on Cycle 1 Day 4 Consolidation period: Pre-dose, 1, 2, 4, 6, 10, and 24 hours post-dose on Cycle 1 Day 1

  4. Phase 1 Part: Area Under The Concentration-Time Curve From The Time Zero to The Last Measurable Concentration (AUClast) of Gilteritinib Concomitant With Induction and Consolidation Chemotherapy

    AUClast was derived from the PK samples collected. It was planned that standard deviation(SD) would only be calculated if there are more than 3 participants analyzed otherwise, SD was not calculated.

    Measured: Induction period: Pre-dose, 1, 2, 4, 6, 10, and 24 hours post-dose on Cycle 1 Day 4 Consolidation period: Pre-dose, 1, 2, 4, 6, 10, and 24 hours post-dose on Cycle 1 Day 1

  5. Phase 1 Part: Plasma Trough Concentration (Ctrough) of Gilteritinib Concomitant With Induction and Consolidation Chemotherapy

    Ctrough is the plasma concentration prior to drug administration. It was planned that standard deviation(SD) would only be calculated if there are more than 3 participants analyzed otherwise, SD was not calculated.

    Measured: Induction period: Pre-dose on Cycle 1 Day 8, 11, and 17 Consolidation period: Pre-dose on Cycle 1 Day 6 and 15

  6. Phase 1 Part: Plasma Trough Concentration of Cytarabine Concomitant With Gilteritinib With Induction and Consolidation Period

    Ctrough is the plasma concentration prior to drug administration. It was planned that standard deviation(SD) would only be calculated if there are more than 3 participants analyzed otherwise, SD was not calculated.

    Measured: Induction period: Predose on Cycle 1 Day 1, 3, and 8 Consolidation period: Predose on Cycle 1 Day 2 and 6

  7. Phase 2 Part: Plasma Trough Concentration of Gilteritinib Concomitant With Induction and Consolidation Chemotherapy

    Ctrough is the plasma concentration prior to drug administration.

    Measured: Induction period : Predose on Cycle 1 Day 15 and 21 Consolidation period: Predose on Cycle 1 Day 8 and 15

  8. Phase 2 Part: Overall Survival (OS)

    Overall survival (OS) was defined as the time from the date of first dose of day 1 to the date of death due to any cause. Participants still alive or lost to follow up was censored at the time they were last known to be alive. Kaplan-Meier (KM) estimate was used for analysis.

    Measured: From the date of first dose up to the date of death (maximum duration: approximately 4.4 years)

  9. Phase 2 Part: Event Free Survival (EFS)

    Event-free survival (EFS): time from date of first dose of study regimen until date of documented relapse, treatment failure or death from any cause, whichever occurred first. KM estimate was used for analysis. Relapse: reappearance of leukemic blasts in peripheral blood (>2%)/≥ 5% blasts in bone marrow aspirate (BMA)/reappearance of significant numbers of peripheral blasts and an increase in percentage of blasts in BMA to > 25%. Treatment failure: participants who failed to achieve composite complete remission (CRc) or who discontinued treatment due to "lack of efficacy" without previous response. CRc: rate of all complete \& incomplete remissions i.e. CR + CR with incomplete platelet recovery (CRp) + CR with incomplete hematological recover (CRi). CRp: met all CR criteria at post-baseline visit, except unrecovered platelet count (< 100,000/mm^3). CRi: met all CR criteria at post-baseline visit, except unrecovered neutrophil count (< 1,000/mm^3). CR: defined in outcome measure #5.

    Measured: From the date of first dose up to the date of documented relapse, treatment failure or death from any cause (maximum duration: approximately 4.4 years)

  10. Phase 2 Part: Relapse Free Survival (RFS)

    Relapse-free survival (RFS): time from date of achievement of first CRc until relapse or death from any cause. KM estimate was used for analysis.

    Relapse: reappearance of leukemic blasts in peripheral blood (>2%)/≥ 5% blasts in bone marrow aspirate (BMA)/reappearance of significant numbers of peripheral blasts and an increase in percentage of blasts in BMA to > 25%.

    CRc: rate of all complete \& incomplete remissions i.e. CR + CR with incomplete platelet recovery (CRp) + CR with incomplete hematological recover (CRi).

    CRp: met all CR criteria at post-baseline visit, except unrecovered platelet count (< 100,000/mm^3).

    CRi: met all CR criteria at post-baseline visit, except unrecovered neutrophil count (< 1,000/mm^3).

    CR: morphologically leukemia-free state at post-baseline visit, having neutrophil count of ≥ 1,000/mm^3 and platelet count of ≥ 100,000/mm^3, bone marrow blasts < 5%. No evidence of Auer rods \& extramedullary leukemia. Blast counts in peripheral blood was ≤ 2%.

    Measured: From the date of achievement of first CRc up to the date of documented relapse or death from any cause (maximum duration: approximately 3.9 years)

  11. Phase 2 Part: CR Rate After Consolidation and Maintenance Period

    Percentage of participants with CR was reported. CR was defined as a morphologically leukemia-free state at the post-baseline visit, having a neutrophil count of ≥ 1,000/mm^3 and platelet count of ≥ 100,000/mm^3, bone marrow blasts < 5%. No evidence of Auer rods and no evidence of extramedullary leukemia. The blast counts in peripheral blood was ≤ 2%. Derived response assessment after the consolidation period refers to the best response from the start of treatment in the induction period until the end of the consolidation period and for the maintenance period refers to the best response from the start of treatment in the induction period until the end of the maintenance period.

    Measured: CP: From date of first dose up to end of period (approximately 1.8 years), MP: From date of first dose up to the end of period (approximately 3.8 years)

  12. Phase 2 Part: CR Rate Without Minimal Residual Disease (MRD) After Each Treatment Therapy Period

    CR% without MRD reported. CR rate without MRD after each treatment therapy was defined similarly as CR rate after each treatment therapy. Responders achieve that the best response is CR and MRD status was negative. CR was defined as a morphologically leukemia-free state, having a neutrophil count of ≥ 1,000/mm^3 and platelet count of ≥ 100,000/mm^3, bone marrow blasts < 5%. No evidence of Auer rods and extramedullary leukemia. The blast counts in peripheral blood was ≤ 2%. Derived response assessment after the IP refers to the best response from the start of treatment in the IP until the end of the IP, after CP refers to the best response from the start of treatment in the IP until the end of the CP and for the MP refers to the best response from the start of treatment in the IP until the end of the MP.

    Measured: IP: From date of first dose up to end of period (approximately 1.4 years), CP: From date of first dose up to end of period (approximately 1.8 years), MP: From date of first dose up to the end of period (approximately 3.8 years)

  13. Phase 2 Part: CR With Partial Hematological Recovery (CRh) Rate After Each Treatment Therapy Period

    Percentage of participants with CRh was reported. CRh was defined as a condition at the post baseline visit, having bone marrow blasts < 5%, partial hematologic recovery neutrophil count≥ 500/mm^3 and platelet count ≥ 50,000/mm^3, no evidence of extramedullary leukemia and could be classified as CR. The blast counts in peripheral blood was ≤ 2%. Derived response assessment after the IP refers to the best response from the start of treatment in the IP until the end of the IP, after CP refers to the best response from the start of treatment in the IP until the end of the CP and for the MP refers to the best response from the start of treatment in the IP until the end of the MP.

    Measured: IP: From date of first dose up to end of period (approximately 1.4 years), CP: From date of first dose up to end of period (approximately 1.8 years), MP: From date of first dose up to the end of period (approximately 3.8 years)

  14. Phase 2 Part: Composite CR (CRc) Rate After Each Treatment Therapy Period

    Percentage of participants with CRc reported. CRc: rate of all complete \& incomplete remissions i.e. CR + CR with incomplete platelet recovery (CRp) + CR with incomplete hematological recovery (CRi). CRp: met all CR criteria, except unrecovered platelet count (< 100,000/mm^3). CRi: met all CR criteria, except unrecovered neutrophil count (< 1,000/mm^3). CR: morphologically leukemia-free state, having neutrophil count of ≥ 1,000/mm^3 and platelet count of ≥ 100,000/mm^3, bone marrow blasts < 5%. No evidence of Auer rods \& extramedullary leukemia. Blast counts in peripheral blood was ≤ 2%. Derived response assessment after the IP refers to the best response from the start of treatment in the IP until the end of the IP, after CP refers to the best response from the start of treatment in the IP until the end of the CP and for the MP refers to the best response from the start of treatment in the IP until the end of the MP.

    Measured: IP: From date of first dose up to end of period (approximately 1.4 years), CP: From date of first dose up to end of period (approximately 1.8 years), MP: From date of first dose up to the end of period (approximately 3.8 years)

  15. Phase 2 Part: CR/CRh Rate After Each Treatment Therapy Period

    Percentage of participants with CR/CRh was reported. CR was defined as a morphologically leukemia-free state at the post-baseline visit, having a neutrophil count of ≥ 1,000/mm^3 and platelet count of ≥ 100,000/mm^3, bone marrow blasts < 5%. No evidence of Auer rods and no evidence of extramedullary leukemia. The blast counts in peripheral blood was ≤ 2%. CRh was defined as a condition at the post baseline visit, having bone marrow blasts < 5%, partial hematologic recovery neutrophil count≥ 500/mm^3 and platelet count ≥ 50,000/mm^3, no evidence of extramedullary leukemia and could be classified as CR. The blast counts in peripheral blood was ≤ 2%. Derived response assessment after the IP refers to the best response from the start of treatment in the IP until the end of the IP, after CP refers to the best response from the start of treatment in the IP until the end of the CP and for the MP refers to the best response from the start of treatment in the IP until the end of the MP.

    Measured: IP: From date of first dose up to end of period (approximately 1.4 years), CP: From date of first dose up to end of period (approximately 1.8 years), MP: From date of first dose up to the end of period (approximately 3.8 years)

  16. Phase 2 Part: Duration of CR

    Duration of CR was defined as the time from the date of achieving first CR until the date of first documented relapse for participants who achieved CR. KM estimate was used for analysis.

    CR was defined as a morphologically leukemia-free state at the post-baseline visit, having a neutrophil count of ≥ 1,000/mm^3 and platelet count of ≥ 100,000/mm^3, bone marrow blasts < 5%. No evidence of Auer rods and no evidence of extramedullary leukemia. The blast counts in peripheral blood was ≤ 2%.

    Relapse: reappearance of leukemic blasts in peripheral blood (>2%)/≥ 5% blasts in BMA/reappearance of numbers of peripheral blasts and an increase in percentage of blasts in BMA to > 25%.

    Measured: From the date of achieving CR up to the date of documented relapse (maximum duration: approximately 2.6 years)

  17. Phase 2 Part: Duration of CR/CRh

    Duration of CR/CRh is defined as the time from the date of achieving first CR/CRh until the date of first documented relapse for participants who achieved CR/CRh. KM estimate was used for analysis. CR was defined as a morphologically leukemia-free state at the post-baseline visit, having a neutrophil count of ≥ 1,000/mm^3 and platelet count of ≥ 100,000/mm^3, bone marrow blasts < 5%. No evidence of Auer rods and no evidence of extramedullary leukemia. The blast counts in peripheral blood was ≤ 2%. CRh was defined as a condition at the post baseline visit, having bone marrow blasts < 5%, partial hematologic recovery neutrophil count≥ 500/mm^3 and platelet count ≥ 50,000/mm^3, no evidence of extramedullary leukemia and could be classified as CR. The blast counts in peripheral blood was ≤ 2%.

    Relapse: reappearance of leukemic blasts in peripheral blood (>2%)/≥ 5% blasts in BMA/reappearance of numbers of peripheral blasts and an increase in percentage of blasts in BMA to > 25%.

    Measured: From the date of achieving CR/CRh up to the date of documented relapse (maximum duration: approximately 2.6 years)

  18. Phase 2 Part: Duration of CRh

    Duration of CRh was defined as the time from date of achieving first CRh until date of first documented relapse for participants who achieved CRh. KM estimate was used for analysis. CRh was defined as a condition at the post baseline visit, having bone marrow blasts < 5%, partial hematologic recovery neutrophil count≥ 500/mm^3 and platelet count ≥ 50,000/mm^3, no evidence of extramedullary leukemia and could be classified as CR. The blast counts in peripheral blood was ≤ 2%.

    Relapse: reappearance of leukemic blasts in peripheral blood (>2%)/≥ 5% blasts in BMA/reappearance of numbers of peripheral blasts and an increase in percentage of blasts in BMA to > 25%.

    Measured: From the date of achieving CRh up to the date of documented relapse (maximum duration: approximately 2.6 years)

  19. Phase 2 Part: Duration of CRc

    Duration of CRc is defined as the time from the date of achieving first CRc until the date of first documented relapse for participants who achieved CRc. KM estimate was used for analysis. CRc: rate of all complete \& incomplete remissions i.e. CR + CR with incomplete platelet recovery (CRp) + CR with incomplete hematological recover (CRi). CRp: met all CR criteria at post-baseline visit, except unrecovered platelet count (< 100,000/mm^3). CRi: met all CR criteria at post-baseline visit, except unrecovered neutrophil count (< 1,000/mm^3). CR: morphologically leukemia-free state at post-baseline visit, having neutrophil count of ≥ 1,000/mm^3 and platelet count of ≥ 100,000/mm^3, bone marrow blasts < 5%. No evidence of Auer rods \& extramedullary leukemia. Blast counts in peripheral blood was ≤ 2%.

    Relapse: reappearance of leukemic blasts in peripheral blood (>2%)/≥ 5% blasts in BMA/reappearance of numbers of peripheral blasts and an increase in percentage of blasts in BMA to > 25%.

    Measured: From the date of achieving CRc up to the date of documented relapse (maximum duration: approximately 2.7 years)

  20. Phase 2 Part: Duration of Response (DoR)

    DoR: from first day of achieving CRc (CR+ CRp,+CRi)/partial remission (PR) to first day of relapse. KM estimate was used for analysis. CR: morphologically leukemia-free state at post-baseline visit, having neutrophil count of ≥ 1,000/mm^3 \& platelet count of ≥ 100,000/mm^3, bone marrow blasts < 5%. No evidence of Auer rods \& extramedullary leukemia. Peripheral blood blast counts was ≤ 2%. CRp: met all CR criteria at post-baseline visit, except unrecovered platelet count (< 100,000/mm^3). CRi: met all CR criteria at post-baseline visit, except unrecovered neutrophil count (< 1,000/mm^3). PR: condition with regeneration of normal hematopoietic cells in bone marrow, no detectable blasts, ≥ 50% decrease of blasts in BMA \& total bone marrow blasts of 5-25%. No evidence of extramedullary leukemia. Relapse: reappearance of leukemic blasts in peripheral blood (>2%)/≥ 5% blasts in BMA/reappearance of numbers of peripheral blasts and an increase in percentage of blasts in BMA to > 25%

    Measured: From the date of achieving CR, CRp, CRi/PR up to the date of documented relapse (maximum duration: approximately 2.7 years)

  21. Phase 2 Part: Number of Participants With Treatment Emergent Adverse Events (TEAEs)

    An AE was defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE could therefore be any unfavorable \& unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. TEAE for Phase 2 was defined as an AE observed after the date of first dose until 30 days after the last dose. TEAE included both serious and non-serious AEs.

    Measured: From the date of first dose up to 30 days after the last dose ( maximum duration up to approximately 4.4 years)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Dec 2014 (estimated)
  2. Study start26 Feb 2015
  3. Primary completion25 Aug 2021
  4. Study completion9 Jul 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
97 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02310321
Sponsor's protocol ID
2215-CL-0104
Status last verified
Aug 2025
First submitted
1 Dec 2014
Last updated
2 Sep 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as products terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.

Publications

  • Sawa M, Miyamoto T, Kim HJ, Hiramatsu Y, Cheong JW, Ikezoe T, Naoe T, Akashi K, Morita S, Kosako M, Shimura M, Terada W, Kadokura T, Hill J, Miyawaki S, Gill SC, Heinloth A, Hasabou N. A phase I/II study of gilteritinib in combination with chemotherapy in newly diagnosed patients with AML in Asia: final analysis. Ther Adv Hematol. 2026 Mar 11;17:20406207261419953. doi: 10.1177/20406207261419953. eCollection 2026.

    PubMed 41835842

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Gilteritinib, Idarubicin and Cytarabine in people with Acute Myeloid Leukemia and FLT3-mutated Acute Myeloid Leukemia, run by Astellas Pharma Inc at 55 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 41 inclusion and 57 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 55 sites in Japan, South Korea, Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 16 Oct 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase 1 Part: Maximum Tolerated Dose (MTD) of Gilteritinib (time frame: Day 1 up to the end of Induction period cycle 1 (up to 42 days)). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02310321, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Sep 2025.

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