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Trial record 1 of 1 for:    NCT02014558
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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 currently recruiting participants. (see Contacts and Locations)
Verified November 2014 by Astellas Pharma Inc
Sponsor:
Information provided by (Responsible Party):
Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )
ClinicalTrials.gov Identifier:
NCT02014558
First received: November 6, 2013
Last updated: November 17, 2014
Last verified: November 2014
  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: ASP2215
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: 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:

Primary Outcome Measures:
  • Safety and Tolerability assessed through adverse events to determine maximum tolerated dose [ Time Frame: up to 18 months ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Time to attain Cmax


Secondary Outcome Measures:
  • Response Rate [ Time Frame: up to 18 months ] [ Designated as safety issue: No ]
  • Overall Survival [ Time Frame: up to 18 months ] [ Designated as safety issue: No ]
  • Event Free Survival [ Time Frame: Up to 18 months ] [ Designated as safety issue: No ]
  • Leukemia free survival [ Time Frame: up to 18 months ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Time to attain Cmax for midazolam as single agent and when combined with ASP2215


Estimated Enrollment: 230
Study Start Date: October 2013
Estimated Study Completion Date: June 2018
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dose Escalation Cohort Drug: ASP2215
tablet
Experimental: Dose Expansion Cohort Drug: ASP2215
tablet

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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.

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
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02014558

Contacts
Contact: Astellas Pharma Global Development 800-888-7704 ext 5473 Astellas.registration@astellas.com

Locations
United States, Alabama
University of Alabama at Birmingham Recruiting
Birmingham, Alabama, United States, 35294
United States, Arizona
Mayo Clinic Recruiting
Scottsdale, Arizona, United States, 85259
United States, California
City of Hope National Medical Center Recruiting
Duarte, California, United States, 91010
UCLA Medical Center Not yet recruiting
Los Angeles, California, United States, 90095-1678
University of California - San Francisco Recruiting
San Francisco, California, United States, 94143
United States, Illinois
Northwestern University Medical Center Recruiting
Chicago, Illinois, United States, 60611
University of Chicago Medical Center Recruiting
Chicago, Illinois, United States, 60637
United States, Maryland
Johns Hopkins University Recruiting
Baltimore, Maryland, United States, 21209
University of Maryland Medical Center Recruiting
Baltimore, Maryland, United States, 21201
United States, Minnesota
University of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55455
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
United States, New Jersey
Hackensack University Medical Center Recruiting
Hackensack, New Jersey, United States, 07601
United States, New York
Roswell Park Cancer Institute Recruiting
Buffalo, New York, United States, 14263
Columbia University Medical Center Recruiting
New York, New York, United States, 10032
Weill Cornell Medical College Recruiting
New York, New York, United States, 10065
United States, Pennsylvania
Penn State Milton S. Hershey Medical Center Recruiting
Hershey, Pennsylvania, United States, 17033
University of Pennsylvania-Abramson CCC-Dept.of Hem Onc Recruiting
Philadelphia, Pennsylvania, United States, 19104
United States, South Carolina
Medical Center for the University of South Carolina Recruiting
Charleston, South Carolina, United States, 29425-8900
United States, Tennessee
Vanderbilt University Medical Center Recruiting
Nashville, Tennessee, United States, 37232
United States, Texas
MD Anderson Cancer Ctr Recruiting
Houston, Texas, United States, 77030
United States, Virginia
Virginia Cancer Specialists Recruiting
Fairfax, Virginia, United States, 22031
Sponsors and Collaborators
Astellas Pharma Global Development, Inc.
Investigators
Study Director: Executive Medical Director Astellas Pharma Global Development
  More Information

No publications provided

Responsible Party: Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )
ClinicalTrials.gov Identifier: NCT02014558     History of Changes
Other Study ID Numbers: 2215-CL-0101
Study First Received: November 6, 2013
Last Updated: November 17, 2014
Health Authority: United States: Food and Drug Administration
Italy: The Italian Medicines Agency
France: Agence Nationale de Sécurité du Médicament et des produits de santé
Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Astellas Pharma Inc:
Acute Myeloid Leukemia
ASP2215

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

ClinicalTrials.gov processed this record on November 24, 2014