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

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ClinicalTrials.gov Identifier: NCT02310321
Recruitment Status : Active, not recruiting
First Posted : December 8, 2014
Last Update Posted : November 27, 2018
Sponsor:
Information provided by (Responsible Party):
Astellas Pharma Inc

Brief Summary:
The purpose of this study is 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). Safety and tolerability of ASP2215 will also be evaluated. This study will also characterize the pharmacokinetic (PK) parameters of ASP2215 concomitant with induction and consolidation chemotherapy as well as evaluate the PK parameters of cytarabine concomitant with ASP2215.

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia Drug: gilteritinib Drug: Idarubicin Drug: Cytarabine Phase 1

Detailed Description:

This study is composed of the dose-evaluation part and the expansion part.

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

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


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 13 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Study of ASP2215 - A Phase 1 Study of ASP2215 in Combination With Induction and Consolidation Chemotherapy in Patients With Newly Diagnosed Acute Myeloid Leukemia
Actual Study Start Date : February 26, 2015
Estimated Primary Completion Date : April 2019
Estimated Study Completion Date : April 2020


Arm Intervention/treatment
Experimental: A2215 Dose Evaluation Part
In the dose-evaluation part, subjects will receive ASP2215 at assigned single dose for determination of MTD and/or RED. Treatment of AML in this study is composed of 3 periods of therapy: remission induction, consolidation, and maintenance. The decision of whether or not to proceed to the next dose will be made based on the occurrence of DLT during Cycle 1 of the induction period.
Drug: gilteritinib
Once-daily repeated oral administration in every period
Other Name: ASP2215

Drug: Idarubicin
Induction period: Once-daily intravenous injection of 12 mg/m2 idarubicin on 3 consecutive days.

Drug: Cytarabine
Induction period: Once-daily intravenous injection of 100 mg/m2 cytarabine on 7 consecutive days. Consolidation period: Twice-daily intravenous injection of 1.5 g/m2 cytarabine at 12-hour intervals on Days 1, 3, and 5.

Experimental: A2215 Dose Expansion Part
In the expansion part, subjects will receive ASP2215 at RED that has been determined in the dose-evaluation part, and the safety will be assessed based on the onset of DLTs during Cycle 1 of the induction and consolidation periods.
Drug: gilteritinib
Once-daily repeated oral administration in every period
Other Name: ASP2215

Drug: Idarubicin
Induction period: Once-daily intravenous injection of 12 mg/m2 idarubicin on 3 consecutive days.

Drug: Cytarabine
Induction period: Once-daily intravenous injection of 100 mg/m2 cytarabine on 7 consecutive days. Consolidation period: Twice-daily intravenous injection of 1.5 g/m2 cytarabine at 12-hour intervals on Days 1, 3, and 5.




Primary Outcome Measures :
  1. Safety assessed by development of DLT, AEs, laboratory parameters, vital signs, body weight, 12-lead ECG, including QT assessment and ophthalmology [ Time Frame: Up to 28 days after the last administration of ASP2215 ]
    Dose-Limiting Toxicity (DLT), Adverse Event (AE), Electrocardiogram (ECG), QT interval (QT)


Secondary Outcome Measures :
  1. Pharmacokinetics of plasma ASP2215: Cmax [ Time Frame: Days 4, 5, 8, 11, 17 and 28 for induction period, Days 1, 2 ,6 and 15 for consolidation period and discontinuation or the end of Cycle 26 for Maintenance period ]
    Maximum concentration (Cmax)

  2. Pharmacokinetics of plasma ASP2215: tmax [ Time Frame: Days 4, 5, 8, 11, 17 and 28 for induction period, Days 1, 2 ,6 and 15 for consolidation period and discontinuation or the end of Cycle 26 for Maintenance period ]
    Time to attain Cmax (tmax)

  3. Pharmacokinetics of plasma ASP2215: AUC24 [ Time Frame: Days 4, 5, 8, 11, 17 and 28 for induction period, Days 1, 2 ,6 and 15 for consolidation period and discontinuation or the end of Cycle 26 for Maintenance period ]
    Area under plasma concentration-time curve from time 0 to 24 (AUC24)

  4. Pharmacokinetics of plasma ASP2215: CL/F [ Time Frame: Days 4, 5, 8, 11, 17 and 28 f for induction period, Days 1, 2 ,6 and 15 for consolidation period and discontinuation or the end of Cycle 26 for Maintenance period ]
    Oral clearance (CL/F)

  5. Pharmacokinetics of plasma ASP2215: AUClast [ Time Frame: Days 4, 5, 8, 11, 17 and 28 for induction period, Days 1, 2 ,6 and 15 for consolidation period and discontinuation or the end of Cycle 26 for Maintenance period ]
    Area under the plasma concentration-time curve from time 0 to last measurable concentration (AUClast)

  6. Pharmacokinetics of plasma ASP2215: t1/2 [ Time Frame: Days 4, 5, 8, 11, 17 and 28 for induction period, Days 1, 2 ,6 and 15 for consolidation period and discontinuation or the end of Cycle 26 for Maintenance period ]
    Apparent terminal elimination half-life (t1/2)

  7. Pharmacokinetics of plasma ASP2215: Vz/F [ Time Frame: Days 4, 5, 8, 11, 17 and 28 for induction period, Days 1, 2 ,6 and 15 for consolidation period and discontinuation or the end of Cycle 26 for Maintenance period ]
    Apparent Volume of Distribution During the Terminal Elimination Phase after Oral Dosing (Vz/F)

  8. Pharmacokinetics of plasma ASP2215: Ctrough [ Time Frame: Days 4, 5, 8, 11, 17 and 28 for induction period, Days 1, 2 ,6 and 15 for consolidation period and discontinuation or the end of Cycle 26 for Maintenance period ]
    Plasma trough concentration (Ctrough)

  9. Pharmacokinetics of plasma cytarabine: Ctrough [ Time Frame: Day 1, 3, and 8 for Induction period, Day 2 and 6 for Consolidation period and discontinuation or the end of Cycle 26 for Maintenance period ]
    Plasma trough concentration (Ctrough)



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Ages Eligible for Study:   18 Years to 69 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02310321


Locations
Japan
Site JP00003
Aichi, Japan
Site JP00001
Fukuoka, Japan
Site JP00002
Gunma, Japan
Site JP00007
Hyogo, Japan
Site JP00006
Kanagawa, Japan
Site JP00005
Tokyo, Japan
Sponsors and Collaborators
Astellas Pharma Inc
Investigators
Study Director: Medical Director Astellas Pharma Inc

Responsible Party: Astellas Pharma Inc
ClinicalTrials.gov Identifier: NCT02310321     History of Changes
Other Study ID Numbers: 2215-CL-0104
First Posted: December 8, 2014    Key Record Dates
Last Update Posted: November 27, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Astellas Pharma Inc:
Acute Myeloid Leukemia
Cytarabine
Idarubicin
ASP2215

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms
Cytarabine
Idarubicin
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors