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Dose Escalation Study to Investigate the Safety, Tolerability and Pharmacokinetics of ASP2215 in Japanese Patients With Relapsed or Refractory Acute Myeloid Leukemia

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ClinicalTrials.gov Identifier: NCT02181660
Recruitment Status : Completed
First Posted : July 4, 2014
Last Update Posted : December 24, 2018
Sponsor:
Information provided by (Responsible Party):
Astellas Pharma Inc

Tracking Information
First Submitted Date  ICMJE July 2, 2014
First Posted Date  ICMJE July 4, 2014
Last Update Posted Date December 24, 2018
Actual Study Start Date  ICMJE June 16, 2014
Actual Primary Completion Date June 27, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 5, 2016)
Safety and Tolerability assessed through adverse events to determine maximum tolerated dose [ Time Frame: Up to 17 months ]
Original Primary Outcome Measures  ICMJE
 (submitted: July 2, 2014)
Safety and Tolerability assessed through adverse events to determine maximum tolerated dose [ Time Frame: up to 18 months ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 8, 2018)
  • Response Rate [ Time Frame: Up to 16 months ]
    Response Rate includes following parameters; CR rate, composite CR [CR + CRp + CRi] rate, overall response rate [CRc + PR], duration of response
  • Pharmacokinetics of ASP2215 in plasma: AUCinf [ Time Frame: Cycle 0 Day -2 through Cycle 1 Day 1 ]
    Area under the concentration-time curve from the time of dosing extrapolated to time infinity
  • Pharmacokinetics of ASP2215 in plasma: AUClast [ Time Frame: Cycle 0 Day -2 through Cycle 1 Day 1 ]
    Area under the concentration-time curve from the time of dosing to the last measurable concentration
  • Pharmacokinetics of ASP2215 in plasma: AUC24 [ Time Frame: Cycle 0 Day -2 through Cycle 1 Day 1 ]
    Area under the plasma concentration time curve from time 0 to 24 hours
  • Pharmacokinetics of ASP2215 in plasma: AUC48 [ Time Frame: Cycle 0 Day -2 through Cycle 1 Day 1 ]
    Area under the plasma concentration time curve from time 0 to 48 hours
  • Pharmacokinetics of ASP2215 in plasma: Cmax [ Time Frame: Cycle 0 Day -2 through Cycle 1 Day 1 and Cycle 1 Day 28 ]
    Maximum concentration
  • Pharmacokinetics of ASP2215 in plasma: C24 [ Time Frame: Cycle 0 Day -2 through Cycle 1 Day 1 and Cycle 1 Day 28 ]
    Concentration at 24 hours
  • Pharmacokinetics of ASP2215 in plasma: CLF [ Time Frame: Cycle 0 Day -2 through Cycle 1 Day 1 and Cycle 1 Day 28 ]
    Oral clearance
  • Pharmacokinetics of ASP2215 in plasma: Lambda z [ Time Frame: Cycle 0 Day -2 through Cycle 1 Day 1 ]
    Terminal first order elimination rate constant
  • Pharmacokinetics of ASP2215: tmax [ Time Frame: Cycle 0 Day -2 through Cycle 1 Day 1 and Cycle 1 Day 28 ]
    Time to attain Cmax
  • Pharmacokinetics of ASP2215 in plasma: t1/2 [ Time Frame: Cycle 0 Day -2 through Cycle 1 Day 1 ]
    Apparent terminal elimination half-life
  • Pharmacokinetics of ASP2215 in plasma: Vz/F [ Time Frame: Cycle 0 Day -2 through Cycle 1 Day 1 ]
    Apparent volume of distribution during the terminal elimination phase after oral dosing
  • Pharmacokinetics of ASP2215 in plasma: AUCtau [ Time Frame: Cycle 1 Day 28 ]
    Area under the plasma concentration time curve during a dosing interval
  • Pharmacokinetics of ASP2215 in plasma: PTR [ Time Frame: Cycle 1 Day 28 ]
    Peak-trough ratio
  • Pharmacokinetics of ASP2215 in plasma: Rac(AUC) [ Time Frame: Cycle 1 Day 28 ]
    Accumulation ratio calculated using the area under the concentration-time curve
  • Pharmacokinetics of ASP2215 in plasma: Rac(Cmax) [ Time Frame: Cycle 1 Day 28 ]
    Accumulation ratio calculated using the maximum concentration
  • Pharmacokinetics of ASP2215 in plasma: Rac derived t1/2 [ Time Frame: Cycle 1 Day 28 ]
    t1/2 derived from accumulation index
  • Pharmacokinetics of ASP2215 in plasma: Ctrough [ Time Frame: Cycle 1 Day 8, Day 15, Day 22, Day 28 and Day 29 ]
    Plasma trough concentration
  • Pharmacokinetics of ASP2215 in urine: Ae24 [ Time Frame: Cycle 0 Day -2 through Cycle 1 Day 1 ]
    Amount of drug excreted in urine from time 0 to 24 hours
  • Pharmacokinetics of ASP2215 in urine: Ae48 [ Time Frame: Cycle 0 Day -2 through Cycle 1 Day 1 ]
    Amount of drug excreted in urine from time 0 to 48 hours
  • Pharmacokinetics of ASP2215 in urine: Ae24% [ Time Frame: Cycle 0 Day -2 through Cycle 1 Day 1 ]
    Fraction of drug excreted into urine from time 0 to 24 hours as % of dose
  • Pharmacokinetics of ASP2215 in urine: Ae48% [ Time Frame: Cycle 0 Day -2 through Cycle 1 Day 1 ]
    Fraction of drug excreted into urine from time 0 to 48 hours as % of dose
  • Pharmacokinetics of ASP2215 in urine: CLR [ Time Frame: Cycle 0 Day -2 through Cycle 1 Day 1 and Cycle 1 Day 28 ]
    Renal clearance
  • Pharmacokinetics of ASP2215 in urine: Aetau [ Time Frame: Cycle 1 Day 28 ]
    Amount of drug excreted in urine during a dosing interval
  • Pharmacokinetics of ASP2215 in urine: Aetau % [ Time Frame: Cycle 1 Day 28 ]
    Fraction of drug excreted in urine during a dosing interval
Original Secondary Outcome Measures  ICMJE
 (submitted: July 2, 2014)
  • Pharmacokinetics of ASP2215: AUC24 [ Time Frame: Day -2 pre-dose and up to Day 28 in Cycle 1 and pre-dose on Day 1 of Cycle 2 ]
    Area under the plasma concentration time curve at 24 hours
  • Pharmacokinetics of ASP2215: Cmax [ Time Frame: Day -2 pre-dose and up to Day 28 in Cycle 1 and pre-dose on Day 1 of Cycle 2 ]
    Maximum concentration
  • Pharmacokinetics of ASP2215: Ctrough [ Time Frame: Day -2 pre-dose and up to Day 28 in Cycle 1 and pre-dose on Day 1 of Cycle 2 ]
    Minimum Concentration
  • Pharmacokinetics of ASP2215: tmax [ Time Frame: Day -2 pre-dose and up to Day 28 in Cycle 1 and pre-dose on Day 1 of Cycle 2 ]
    Time to attain Cmax
  • urinary ASP2215 concentration [ Time Frame: Day -2 pre-dose and up to Day 28 in Cycle 1 and pre-dose on Day 1 of Cycle 2 ]
  • Response Rate [ Time Frame: up to 18 months ]
    Response Rate includes following parameters; CR rate, composite CR [CR + CRp + CRi] rate, overall response rate [CRc + PR], duration of response
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Dose Escalation Study to Investigate the Safety, Tolerability and Pharmacokinetics of ASP2215 in Japanese Patients With Relapsed or Refractory Acute Myeloid Leukemia
Official Title  ICMJE A Phase 1 Open-label, Dose-escalation Study Investigating the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ASP2215 in Japanese Patients With Relapsed or Refractory Acute Myeloid Leukemia
Brief Summary The objectives of this study are to determine the safety and tolerability of ASP2215 as well as the maximum tolerated dose (MTD) based on the onset of dose limiting toxicity (DLT) and/or determine the recommended dose (RD) of ASP2215 for the next phase in subjects with relapsed or treatment-refractory acute myeloid leukemia (AML).
Detailed Description

This study will be conducted to determine the safety, tolerability, PK, PD, and efficacy of single and repeated oral dosing of ASP2215 once daily in patients with relapsed or refractory AML. After the determination of the MTD and/or RD, an expansion cohort might be set to further investigate the safety and efficacy of ASP2215.

This study will consist of a single-dose period (Cycle 0, 2 days) and a repeated-dose period (Cycle 1 and subsequent cycles, each cycle consisting of 28 days). The enrolled subjects will orally receive their assigned single dose in Cycle 0 (Day -2), followed by a 2-day observation period (dosing day inclusive). In Cycle 1 and subsequent cycles (one cycle is defined as 28 days), the subjects will receive oral ASP2215 once daily repeatedly until one of the discontinuation criteria is met. Another dosing regimen may be considered such as dosing twice daily based on the safety and PK data that will become available.

In this study, the Bayesian-Continual Reassessment Method (hereinafter, Bayesian-CRM) will be used as a reference for dose-escalation procedures, and based on the onset of DLTs, the RD level of the subsequent cohort will be set higher or lower. DLTs will be assessed during Cycle 0 and Cycle 1 (30 days).

ASP2215 may be escalated by one dose level if the subject meets the criteria at the end of each cycle after Cycle 1 and the investigator/sub-investigator judges escalation of ASP2215 is of clinical benefit. Dose reduction of ASP2215 will be considered if study drug-related toxicities are observed in a subject.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Acute Myeloid Leukemia (AML)
Intervention  ICMJE Drug: Gilteritinib
oral
Other Name: ASP2215
Study Arms  ICMJE Experimental: Dose Escalation Cohort
ASP2215
Intervention: Drug: Gilteritinib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 24, 2017)
24
Original Estimated Enrollment  ICMJE
 (submitted: July 2, 2014)
36
Actual Study Completion Date  ICMJE June 27, 2016
Actual Primary Completion Date June 27, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Subject is defined as morphologically documented primary or secondary acute myeloid leukemia (AML) according to the World Health Organization (WHO) criteria (2008) and fulfills one of the following:

    • Refractory to prior induction chemotherapy
    • Relapsed after achieving remission with prior therapy
  • Subject has an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
  • Subject's interval from prior treatment to the time of study drug administration is at least 14 days for antineoplastic agents other than ASP2215 (except for hydroxyurea, which is given to control blast cells).
  • Subject's interval from prior treatment to the time of study drug (ASP2215) administration is at least 5 half-lives (if the half-life is unknown, 14 days) for other investigational products or drugs used for immunosuppressive therapy posthematopoietic stem cell transplantation (HSCT).

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 persistent non-hematological toxicities of ≥ Grade 2 (CTCAE v4), with symptoms and objective findings, due to prior AML treatment (including chemotherapy, kinase inhibitors, immunotherapy, investigational products, radiation therapy, and surgery)
  • Subject has received hematopoietic stem cell transplant (HSCT) and falls under either of the following:

    • Is within 2 months of transplant
    • Has persistent and clinically significant graft-versus-host disease requiring treatment
    • Has persistent non-hematological toxicities of ≥ Grade 2 related to the transplant
  • 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 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 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 inhibitors or inducers of CYP3A4 or of P-gp with such exceptions of antibiotics, antifungals, and antivirals that are considered absolutely essential for prevention or treatment of infections and for which the physician judged that there are no interchangeable drugs.
  • Subject requires treatment with concomitant drugs that target serotonin 5HT1R or 5HT2BR receptors or sigma nonspecific 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Japan
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02181660
Other Study ID Numbers  ICMJE 2215-CL-0102
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Plan Description: Access to anonymized individual participant level data will not be provided for this trial as it meets one or more of the exceptions described on www.clinicalstudydatarequest.com under "Sponsor Specific Details for Astellas."
Responsible Party Astellas Pharma Inc
Study Sponsor  ICMJE Astellas Pharma Inc
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director Astellas Pharma Inc
PRS Account Astellas Pharma Inc
Verification Date December 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP