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Open Label Study to Evaluate Safety and Efficacy of 2 Doses of Quizartinib in Patients With Relapsed or Refractory Acute Myeloid Leukemia

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ClinicalTrials.gov Identifier: NCT01565668
Recruitment Status : Completed
First Posted : March 29, 2012
Last Update Posted : December 27, 2018
Sponsor:
Collaborator:
Ambit Biosciences Corporation
Information provided by (Responsible Party):
Daiichi Sankyo, Inc.

Brief Summary:
This study will evaluate two doses of Quizartinib in patients with relapsed or refractory acute myeloid leukemia who are also FMS-like tyrosine kinase - internal tandem duplication ( FLT3-ITD) positive. Patient will be randomly assigned in a 1:1 ratio to one of two treatment arms. Both treatment arms will receive Quizartinib but at different doses. The study treatment is taken orally in 28 day cycles until either disease progression occurs or an unacceptable toxicity occurs. In addition to the study assessments to evaluate the disease, blood will be drawn to measure drug levels and biomarkers. Patients will be followed for survival at three month intervals after the end of treatment.

Condition or disease Intervention/treatment Phase
Leukemia, Myeloid, Acute Drug: AC220 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 76 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2, Randomized, Open-Label Study of the Safety and Efficacy of Two Doses of Quizartinib (AC220; ASP2689) in Subjects With FLT3-ITD Positive Relapsed or Refractory Acute Myeloid Leukemia (AML)
Study Start Date : April 2012
Actual Primary Completion Date : March 2015
Actual Study Completion Date : March 2015


Arm Intervention/treatment
Experimental: AC220 Dose Level 1 Drug: AC220
oral
Other Names:
  • Quizartinib
  • ASP2689

Experimental: AC220 Dose Level 2 Drug: AC220
oral
Other Names:
  • Quizartinib
  • ASP2689




Primary Outcome Measures :
  1. Composite Complete Response (CRc) [ Time Frame: Evaluated after two complete 28 day cycles ]
    CRc is defined as Complete remission (CR) + Complete remission with incomplete platelet recovery (CRp) + Complete remission with incomplete hematological recovery (CRi)

  2. Grade 2 or higher QT interval corrected for heart rate using Fridericia's factor (QTcF) prolongation at each dose level AC220 [ Time Frame: Evaluated after two complete 28 day cycles ]

Secondary Outcome Measures :
  1. Complete Remission (CR) [ Time Frame: Evaluated after two complete 28 day cycles ]
    Subject must have bone marrow regenerating normal hematopoietic cells and achieve a morphologic leukemia-free state (< 5% bone marrow blasts in bone marrow, no blasts with Auer rods and no persistence of extramedullary disease) and must have an absolute neutrophil count (ANC) ≥ 1x109/L and platelet count ≥ 100 x 109/L and they will be red blood cell (RBC) and platelet transfusion independent (defined as 4 weeks without RBC transfusions and 1 week without platelet transfusion).

  2. Overall Survival (OS) [ Time Frame: Evaluated at end of study, up to 6 months ]
    Time from randomization until death

  3. Event free survival (EFS) [ Time Frame: Evaluated at end of study, up to 6 months ]
    Time from randomization until documented relapse or death

  4. Leukemia free survival (LFS) [ Time Frame: Evaluated at end of study, up to 6 months ]
    Time from first CRc until documented relapse or death

  5. Duration of remission [ Time Frame: Evaluated at end of study, up to 6 months ]
    Time from first documented remission until documented relapse

  6. Safety assessed by recording adverse events, laboratory assessments, vital signs, electrocardiograms (ECGs), and Eastern Cooperative Oncology Group (ECOG) performance scores [ Time Frame: Continuous, up to 6 months from study end ]
  7. Time to treatment response (TTR) [ Time Frame: Evaluated at end of study, up to 6 months ]
    Time from randomization until the first measured response

  8. Percentage of subjects undergoing hematopoietic stem cell transplantation (HSCT) [ Time Frame: Evaluated at end of study, up to 6 months ]


Information from the National Library of Medicine

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

Inclusion Criteria:

  • Subject has morphologically documented primary AML or AML secondary to myelodysplastic syndrome (MDS) as defined by the World Health Organization (WHO) criteria, as determined by pathology review at the treating institution and has relapsed or is refractory after 1 second line (salvage) regimen or after HSCT
  • Subject is positive for FLT3-ITD activating mutation in bone marrow or peripheral blood (>10% allelic ratio)
  • ECOG performance status of 0 to 2
  • In the absence of rapidly progressing disease clearly documented by the investigator, the interval from prior treatment to time of AC220 administration will be at least 2 weeks (14 days) for prior cytotoxic agents or at least 5 half-lives for prior noncytotoxic agents, including immunosuppressive therapy post HSCT
  • Persistent chronic clinically significant nonhematological toxicities from prior treatment (including chemotherapy, kinase inhibitors, immunotherapy, experimental agents, radiation, HSCT, or surgery) must be Grade ≤ 1
  • Patients - both males and females - with reproductive potential are eligible

Exclusion Criteria:

  • Subject received previous treatment with AC220
  • Subject has a diagnosis of acute promyelocytic leukemia
  • Subject has a diagnosis of chronic myelogenous leukemia (CML) in blast crisis
  • Subject has AML or antecedent MDS secondary to prior chemotherapy
  • Subject has had HSCT and has either of the following:
  • Donor lymphocyte infusion (DLI) is not permitted during the study or < 30 days prior to study entry
  • Subject has clinically active CNS leukemia. A subject is considered eligible if CNS leukemia is controlled and subject is receiving intrathecal (IT) therapy at study entry. Subjects should continue to receive IT therapy (or cranial radiation) as clinically indicated
  • Subject has received concurrent chemotherapy, immunotherapy, or radiotherapy within 14 days prior to the first dose of AC220, or any ancillary therapy that is considered to be investigational (i.e., used for non-approved indications(s) and in the context of a research investigation) within 30 days or 5 half-lives (whichever is longer) prior to the first dose of study drug
  • Subject requires treatment with concomitant drugs that prolong QT/QTc interval or with 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 requires treatment with anticoagulant therapy
  • Subject has a known positive test for human immunodeficiency virus, hepatitis C, or hepatitis B surface antigen
  • Subject had major surgery within 4 weeks prior to first dose of AC220
  • Subject has uncontrolled or significant cardiovascular disease, including
  • Subject has a pre-existing disorder predisposing the subject to a serious or life-threatening infection (e.g. cystic fibrosis, congenital or acquired immunodeficiency, bleeding disorder, or cytopenias not related to AML)
  • Subject has an active uncontrolled acute or chronic systemic fungal, bacterial, viral, or other infection
  • Subject has any of the following laboratory values:
  • Subject is a female with a positive pregnancy test, pregnant, or breastfeeding
  • Subject has any medical, psychiatric, addictive or other kind of disorder which compromises the ability of the subject to give written informed consent and/or to comply with procedures

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): NCT01565668


  Show 24 Study Locations
Sponsors and Collaborators
Daiichi Sankyo, Inc.
Ambit Biosciences Corporation
Investigators
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Study Director: Global Clinical Leader Daiichi Sankyo, Inc.

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Responsible Party: Daiichi Sankyo, Inc.
ClinicalTrials.gov Identifier: NCT01565668     History of Changes
Other Study ID Numbers: 2689-CL-2004
2011-005408-13 ( EudraCT Number )
First Posted: March 29, 2012    Key Record Dates
Last Update Posted: December 27, 2018
Last Verified: April 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Analytic Code
Time Frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
URL: https://vivli.org/ourmember/daiichi-sankyo/

Keywords provided by Daiichi Sankyo, Inc.:
FLT3-ITD positive Acute Myeloid Leukemia (AML)
AC220
Relapse
Refractory

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