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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:
Information provided by (Responsible Party):
Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )
ClinicalTrials.gov Identifier:
NCT02014558
First received: November 6, 2013
Last updated: February 29, 2016
Last verified: February 2016
  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:
  • Complete Remission (CR) 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

  • Composite CR rate [ Time Frame: up to 18 months ] [ Designated as safety issue: No ]
    CR + Complete remission with incomplete platelet recovery (CRp) + Complete remission with incomplete hematologic recovery (CRi)

  • Best response rate [ Time Frame: up to 18 months ] [ Designated as safety issue: No ]
    Composite complete remission (CRc) + partial remission (PR)

  • Duration of response [ Time Frame: up to 18 months ] [ Designated as safety issue: No ]
  • Pharmacokinetics of cephalexin 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 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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Time to attain Cmax for cephalexin as single agent and when combined with ASP2215


Enrollment: 258
Study Start Date: October 2013
Estimated Study Completion Date: June 2019
Primary Completion Date: November 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   (Adult, Senior)
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.
  • 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
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

  Show 29 Study Locations
Sponsors and Collaborators
Astellas Pharma Global Development, Inc.
Investigators
Study Director: Executive Medical Director Astellas Pharma Global Development
  More Information

Responsible Party: 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: February 29, 2016
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
Individual Participant Data  
Plan to Share IPD: Undecided

Keywords provided by Astellas Pharma Inc:
Acute Myeloid Leukemia
ASP2215

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

ClinicalTrials.gov processed this record on September 23, 2016