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

NCT02310321

Description:

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.

Related Conditions:
  • Acute Myeloid Leukemia
  • Myelodysplastic Syndromes
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: 2215-CL-0104
  • NCT ID: NCT02310321

Conditions

  • Acute Myeloid Leukemia

Interventions

DrugSynonymsArms
gilteritinibASP2215A2215 Dose Evaluation Part
IdarubicinA2215 Dose Evaluation Part
CytarabineA2215 Dose Evaluation Part

Purpose

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
A2215 Dose Evaluation PartExperimentalIn 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.
  • gilteritinib
  • Idarubicin
  • Cytarabine
A2215 Dose Expansion PartExperimentalIn 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.
  • gilteritinib
  • Idarubicin
  • Cytarabine

Eligibility 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.
      
Maximum Eligible Age:69 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description:Dose-Limiting Toxicity (DLT), Adverse Event (AE), Electrocardiogram (ECG), QT interval (QT)

Secondary Outcome Measures

Measure: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
Safety Issue:
Description:Maximum concentration (Cmax)
Measure: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
Safety Issue:
Description:Time to attain Cmax (tmax)
Measure: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
Safety Issue:
Description:Area under plasma concentration-time curve from time 0 to 24 (AUC24)
Measure: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
Safety Issue:
Description:Oral clearance (CL/F)
Measure: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
Safety Issue:
Description:Area under the plasma concentration-time curve from time 0 to last measurable concentration (AUClast)
Measure: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
Safety Issue:
Description:Apparent terminal elimination half-life (t1/2)
Measure: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
Safety Issue:
Description:Apparent Volume of Distribution During the Terminal Elimination Phase after Oral Dosing (Vz/F)
Measure: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
Safety Issue:
Description:Plasma trough concentration (Ctrough)
Measure: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
Safety Issue:
Description:Plasma trough concentration (Ctrough)

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Astellas Pharma Inc

Trial Keywords

  • Acute Myeloid Leukemia
  • Cytarabine
  • Idarubicin
  • ASP2215

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