Clinical Trials /

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

NCT02014558

Description:

The objective of this study was to assess the safety and tolerability, including the maximum tolerated dose, of gilteritinib in participants with relapsed or treatment-refractory acute myeloid leukemia (AML). This study also determined the pharmacokinetic (PK) parameters of gilteritinib.

Related Conditions:
  • Chronic Myeloid Leukemia
Recruiting Status:

Completed

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Dose Escalation Study Investigating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics of ASP2215 in Patients With Relapsed or Refractory <span class="go-doc-concept go-doc-disease">Acute Myeloid Leukemia</span>

Title

  • Brief Title: Dose Escalation Study Investigating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics of ASP2215 in Patients With Relapsed or Refractory Acute Myeloid Leukemia
  • 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
  • Clinical Trial IDs

    NCT ID: NCT02014558

    ORG ID: 2215-CL-0101

    Trial Conditions

    Acute Myeloid Leukemia

    Trial Interventions

    Drug Synonyms Arms
    ASP2215 Dose Escalation Cohort, Dose Expansion Cohort

    Trial 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.

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    Dose Escalation Cohort Experimental ASP2215
    Dose Expansion Cohort Experimental ASP2215

    Eligibility 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.

    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

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Safety and Tolerability assessed through adverse events to determine maximum tolerated dose

    Pharmacokinetics of ASP2215: AUC24

    Pharmacokinetics of ASP2215: Cmax

    Pharmacokinetics of ASP2215: Ctrough

    Pharmacokinetics of ASP2215: tmax

    Secondary Outcome Measures

    Complete Remission (CR) Rate

    Overall Survival

    Event Free Survival

    Leukemia free survival

    Pharmacokinetics of ASP2215 in co-administration with strong or moderate CYP3A4 (Cytochrome P450-isozyme3A4) inhibitors: AUC24

    Pharmacokinetics of ASP2215 in co-administration with strong or moderate CYP3A4 (Cytochrome P450-isozyme3A4) inhibitors: Cmax

    Pharmacokinetics of ASP2215 in co-administration with strong or moderate CYP3A4 (Cytochrome P450-isozyme3A4) inhibitors: Ctrough

    Pharmacokinetics of ASP2215 in co-administration with strong or moderate CYP3A4 (Cytochrome P450-isozyme3A4) inhibitors: tmax

    Pharmacokinetics of midazolam in co-administration with ASP2215: AUC24

    Pharmacokinetics of midazolam in co-administration with ASP2215: Cmax

    Pharmacokinetics of midazolam in co-administration with ASP2215: Ctrough

    Pharmacokinetics of midazolam in co-administration with ASP2215: tmax

    Composite CR rate

    Best response rate

    Duration of response

    Pharmacokinetics of cephalexin in co-administration with ASP2215: AUC24

    Pharmacokinetics of cephalexin in co-administration with ASP2215: Cmax

    Pharmacokinetics of cephalexin in co-administration with ASP2215: Ctrough

    Pharmacokinetics of cephalexin in co-administration with ASP2215: tmax

    Trial Keywords

    Acute Myeloid Leukemia

    ASP2215