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Dose Escalation Study Investigating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics of ASP2215 in Patients With Relapsed or Refractory Acute Myeloid Leukemia

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02014558
First Posted: December 18, 2013
Last Update Posted: October 17, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )
  Purpose
The objective of this study is to assess the safety and tolerability, including the maximum tolerated dose, of ASP2215 in subjects with relapsed or treatment-refractory acute myeloid leukemia (AML). This study will also determine the pharmacokinetic (PK) parameters of ASP2215.

Condition Intervention Phase
Acute Myeloid Leukemia Drug: Gilteritinib Phase 1 Phase 2

Access to an investigational treatment associated with this study is available outside the clinical trial.   More info ...

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2 Open-Label, Dose Escalation Study Investigating the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ASP2215 in Patients With Relapsed or Refractory Acute Myeloid Leukemia

Resource links provided by NLM:


Further study details as provided by Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. ):

Primary Outcome Measures:
  • Safety and Tolerability assessed through adverse events to determine maximum tolerated dose [ Time Frame: up to 18 months ]
  • Pharmacokinetics of ASP2215: AUC24 [ Time Frame: Day -2 pre-dose and up to Day 22 in Cycle 1 and pre-dose on Day 1 of each cycle subsequent 28 day cycle for an expected average of 4 cycles ]
    Area under the plasma concentration time curve at 24 hours

  • Pharmacokinetics of ASP2215: Cmax [ Time Frame: Day -2 pre-dose and up to Day 22 in Cycle 1 and pre-dose on Day 1 of each cycle subsequent 28 day cycle for an expected average of 4 cycles ]
    Maximum Concentration

  • Pharmacokinetics of ASP2215: Ctrough [ Time Frame: Day -2 pre-dose and up to Day 22 in Cycle 1 and pre-dose on Day 1 of each cycle subsequent 28 day cycle for an expected average of 4 cycles ]
    Minimum Concentration

  • Pharmacokinetics of ASP2215: tmax [ Time Frame: Day -2 pre-dose and up to Day 22 in Cycle 1 and pre-dose on Day 1 of each cycle subsequent 28 day cycle for an expected average of 4 cycles ]
    Time to attain Cmax


Secondary Outcome Measures:
  • Complete Remission (CR) Rate [ Time Frame: up to 18 months ]
  • Overall Survival [ Time Frame: up to 18 months ]
  • Event Free Survival [ Time Frame: Up to 18 months ]
  • Leukemia free survival [ Time Frame: up to 18 months ]
  • Pharmacokinetics of ASP2215 in co-administration with strong or moderate CYP3A4 (Cytochrome P450-isozyme3A4) inhibitors: AUC24 [ Time Frame: Pre-dose, Day 1, Cycle 1 and up to Cycle 2, Day 1 ]
    Area under the plasma concentration time curve at 24 hours for ASP2215 as single agent and when combined with CYP3A4 inhibitor

  • Pharmacokinetics of ASP2215 in co-administration with strong or moderate CYP3A4 (Cytochrome P450-isozyme3A4) inhibitors: Cmax [ Time Frame: Pre-dose, Day 1, Cycle 1 and up to Cycle 2, Day 1 ]
    Maximum Concentration for ASP2215 as single agent and when combined with CYP3A4 inhibitor

  • Pharmacokinetics of ASP2215 in co-administration with strong or moderate CYP3A4 (Cytochrome P450-isozyme3A4) inhibitors: Ctrough [ Time Frame: Pre-dose, Day 1, Cycle 1 and up to Cycle 2, Day 1 ]
    Minimum Concentration for ASP2215 as single agent and when combined with CYP3A4 inhibitor

  • Pharmacokinetics of ASP2215 in co-administration with strong or moderate CYP3A4 (Cytochrome P450-isozyme3A4) inhibitors: tmax [ Time Frame: Pre-dose, Day 1, Cycle 1 and up to Cycle 2, Day 1 ]
    Time to attain Cmax for ASP2215 as single agent and when combined with CYP3A4 inhibitor

  • Pharmacokinetics of midazolam in co-administration with ASP2215: AUC24 [ Time Frame: Pre-dose and up to Day 15 in Cycle 1 ]
    Area under the plasma concentration time curve at 24 hours for midazolam as single agent and when combined with ASP2215

  • Pharmacokinetics of midazolam in co-administration with ASP2215: Cmax [ Time Frame: Pre-dose and up to Day 15 in Cycle 1 ]
    Maximum Concentration for midazolam as single agent and when combined with ASP2215

  • Pharmacokinetics of midazolam in co-administration with ASP2215: Ctrough [ Time Frame: Pre-dose and up to Day 15 in Cycle 1 ]
    Minimum Concentration for midazolam as single agent and when combined with ASP2215

  • Pharmacokinetics of midazolam in co-administration with ASP2215: tmax [ Time Frame: Pre-dose and up to Day 15 in Cycle 1 ]
    Time to attain Cmax for midazolam as single agent and when combined with ASP2215

  • Composite CR rate [ Time Frame: up to 18 months ]
    CR + Complete remission with incomplete platelet recovery (CRp) + Complete remission with incomplete hematologic recovery (CRi)

  • Best response rate [ Time Frame: up to 18 months ]
    Composite complete remission (CRc) + partial remission (PR)

  • Duration of response [ Time Frame: up to 18 months ]
  • Pharmacokinetics of cephalexin in co-administration with ASP2215: AUC24 [ Time Frame: Pre-dose and up to Day 15 in Cycle 1 ]
    Area under the plasma concentration time curve at 24 hours for cephalexin as single agent and when combined with ASP2215

  • Pharmacokinetics of cephalexin in co-administration with ASP2215: Cmax [ Time Frame: Pre-dose and up to Day 15 in Cycle 1 ]
    Maximum Concentration for cephalexin as single agent and when combined with ASP2215

  • Pharmacokinetics of cephalexin in co-administration with ASP2215: Ctrough [ Time Frame: Pre-dose and up to Day 15 in Cycle 1 ]
    Minimum Concentration for cephalexin as single agent and when combined with ASP2215

  • Pharmacokinetics of cephalexin in co-administration with ASP2215: tmax [ Time Frame: Pre-dose and up to Day 15 in Cycle 1 ]
    Time to attain Cmax for cephalexin as single agent and when combined with ASP2215


Enrollment: 258
Actual Study Start Date: October 9, 2013
Estimated Study Completion Date: January 2018
Primary Completion Date: November 24, 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dose Escalation Cohort
oral
Drug: Gilteritinib
tablet
Other Name: ASP2215
Experimental: Dose Expansion Cohort
oral
Drug: Gilteritinib
tablet
Other Name: ASP2215

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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

    • Refractory to at least 1 cycle of induction chemotherapy
    • Relapsed after achieving remission with a prior therapy
  • Subject has an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
  • Subject's interval from prior treatment to time of study drug administration is at least 2 weeks for cytotoxic agents (except hydroxyurea given for controlling blast cells), or at least 5 half-lives for prior experimental agents or noncytotoxic agents.
  • Subject must meet the following criteria as indicated on the clinical laboratory tests*:

    • Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <2.5 x institutional upper limit normal (ULN)
    • Total serum bilirubin < 1.5x institutional ULN
    • Serum creatinine < 1.5 x institutional ULN or an estimated glomerular filtration rate (eGFR) of > 50 ml/min as calculated by the Modification of Diet in Renal Disease (MDRD) equation.
  • Subject agrees not to participate in another interventional study while on treatment.

Exclusion Criteria:

  • Subject was diagnosed as acute promyelocytic leukemia (APL).
  • Subject has 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 nonhematological toxicities of >= Grade 2 (Common Terminology Criteria for Adverse Events v4), with symptoms and objective findings, from prior AML treatment (including chemotherapy, kinase inhibitors, immunotherapy, experimental agents, radiation, or surgery).
  • Subject has had hematopoietic stem cell transplant (HSCT) and meets any of the following:

    • Is within 2 months of transplant from C1D1
    • Has clinically significant graft-versus-host disease requiring treatment
    • Has >= Grade 2 persistent non-hematological toxicity related to the transplant. Donor lymphocytes infusion (DLI) is not permitted <= 30 days prior to study registration or during the first cycle of treatment on the study in Cohort 1 and first two cycles of the treatment in Cohort 2
  • Subject has clinically active central nervous system leukemia
  • Subject has disseminated intravascular coagulation abnormality (DIC)
  • Subject has had major surgery within 4 weeks prior to the first study dose.
  • Subject has had radiation therapy within 4 weeks prior to the first study dose
  • Subject has congestive heart failure New York Heart Association (NYHA) class 3 or 4, or subject with a history of congestive heart failure NYHA class 3 or 4 in the past, unless a screening echocardiogram performed within 3 months prior to study entry results in a left ventricular ejection fraction that is ≥ 45%
  • Subject requires treatment with concomitant drugs that are strong inhibitors or inducers of Cytochrome P450-isozyme3A4 (CYP3A4) with the exception of antibiotics, antifungals, and antivirals that are used as standard of care post-transplant or to prevent or treat infections and other such drugs that are considered absolutely essential for the care of the subject
  • Subject required treatment with concomitant drugs that target serotonin 5HT1R or 5HT2BR receptors or sigma nonspecific receptor with the exception of drugs that are considered absolutely essential for the care of the subject.
  • Subject has an active uncontrolled infection
  • Subject is known to have human immunodeficiency virus infection
  • Subject has active hepatitis B or C, or other active hepatic disorder
  Contacts and Locations
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): NCT02014558


  Show 26 Study Locations
Sponsors and Collaborators
Astellas Pharma Global Development, Inc.
Investigators
Study Director: Executive Medical Director Astellas Pharma Global Development
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Astellas Pharma Global Development, Inc.
ClinicalTrials.gov Identifier: NCT02014558     History of Changes
Other Study ID Numbers: 2215-CL-0101
First Submitted: November 6, 2013
First Posted: December 18, 2013
Last Update Posted: October 17, 2017
Last Verified: October 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. ):
Acute Myeloid Leukemia
Gilteritinib
ASP2215

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms