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A Study to Assess AC220 Given in Combination With Induction and Consolidation Therapy in Newly Diagnosed Acute Myeloid Leukemia (AML)

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.
ClinicalTrials.gov Identifier: NCT01390337
Recruitment Status : Completed
First Posted : July 11, 2011
Last Update Posted : February 12, 2019
Ambit Biosciences Corporation
Information provided by (Responsible Party):
Daiichi Sankyo, Inc.

Brief Summary:
The purpose of this study is to define the maximum tolerated dose (MTD) of AC220 when combined with induction and consolidation therapy and as maintenance therapy following induction and consolidation.

Condition or disease Intervention/treatment Phase
Leukemia, Myeloid, Acute Drug: AC220 Drug: daunorubicin Drug: cytarabine Phase 1

Detailed Description:

Subjects will receive escalating doses of AC220 plus standard 7+3 cytarabine and daunorubicin remission induction therapy. Subjects may receive up to 2 cycles of induction therapy. Subjects who have a complete response (including complete remission (CR) with incomplete hematologic recovery) are eligible to receive up to 3 consolidation cycles. In consolidation subjects will receive AC220 plus high dose cytarabine. Subjects achieving a composite Complete Remission (CRc) will be eligible to receive AC220 alone for up to 12 additional 28 day cycles.

Subjects will be enrolled into successive gender balanced cohorts of 6 subjects (at least 3 must be females) to determine the maximum tolerated dose (MTD). Dose escalation decision will be made based on dose limiting toxicities (DLTs) that occur during the first remission induction cycle. Seven and 14 day schedules will be evaluated.

After the MTD and schedule is established, the study will open to enroll between 14 to 34 subjects. Subjects will receive AC220 during induction and consolidation at the MTD and schedule established. Stopping rules will be used to evaluate safety at the current dose. If testing at a dose level must be stopped, then a lower dose may be tested. MTD will also be established for the maintenance therapy.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 19 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Study of AC220 (ASP2689) in Combination With Induction and Consolidation Chemotherapy in Patients With Newly Diagnosed Acute Myeloid Leukemia
Study Start Date : October 2011
Actual Primary Completion Date : February 2015
Actual Study Completion Date : February 2015

Arm Intervention/treatment
Experimental: AC220 Drug: AC220
Oral Liquid
Other Names:
  • quizartinib
  • ASP2689

Drug: daunorubicin
Intravenous Infusion
Other Names:
  • Cerubidine
  • daunorubicin hydrochloride

Drug: cytarabine
Intravenous Infusion
Other Names:
  • Ara-C
  • Cytarabine Hydrochloride
  • Cytosar
  • Cytosine
  • Arabinoside

Primary Outcome Measures :
  1. Safety assessed by recording adverse events, physical examinations, vital signs, electrocardiograms (ECGs), and laboratory assessments [ Time Frame: up to Day 42 ]
  2. Incidence of Dose Limiting Toxicity (DLT) [ Time Frame: up to Day 42 ]

Secondary Outcome Measures :
  1. Pharmacokinetic assessment through analysis of blood samples [ Time Frame: Up to Day 11 ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Subject has a diagnosis of previously-untreated de novo acute myeloid leukemia (AML) according to World Health Organization (WHO) classification (2008) documented within 28 days prior to enrollment and defined as > 20% myeloblasts on the marrow aspirate or peripheral blood differential, with or without extramedullary involvement, with confirmatory immunophenotyping or immunocytochemistry (e.g. myeloperoxidase). In addition, subjects with the clonal, recurring cytogenetic abnormalities: t(8;21)(q22;q22), inv(16)(p13q22) or t(16;16)(p13;q22) should be considered to have AML regardless of the blast percentage. Subjects with both positive and negative FMS-like tyrosine kinase - internal tandem duplication (FLT3-ITD) mutation status are eligible.
  • Subject has an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.
  • Subject must have adequate renal, hepatic, and coagulation parameters as indicated by the following laboratory values:
  • Subject is a woman of childbearing potential (WOCBP) or a male subject with female partner of childbearing potential who agrees to use a medically-approved method of contraception to avoid pregnancy throughout the study and for at least 3 months after the last dose of study drug.
  • Subject is a WOCBP and has a negative serum or urine pregnancy test (sensitivity ≤ 25 IU human chorionic gonadotropin [hCG]/L) within 72 hours prior to the start of study drug administration.
  • Subject is able to comply with study procedures and follow-up examinations.

Exclusion Criteria:

  • Subject has a diagnosis of acute promyelocytic leukemia (APL), French-American-British (FAB) classification M3 or World Health Organization (WHO) classification of APL with t(15;17)(q22;q12), or BCR-ABL positive leukemia (chronic myelogenous leukemia in blast crisis).
  • Subject has a diagnosis of AML following an antecedent hematologic disorder (diagnosis of myelodysplasia or myeloproliferative neoplasm by bone marrow aspirate and/or biopsy documented at least 12 weeks prior to first dose of study drug).
  • Subject has a diagnosis of acute bilineal/biphenotypic leukemia.
  • Subject has therapy-related AML.
  • Subject received previous treatment with AC220.
  • Subject has received previous therapy for AML
  • Subject has uncontrolled disseminated intravascular coagulation.
  • Subject has Central Nervous System (CNS) leukemia. A Subject with symptoms suggestive of CNS leukemia must undergo a lumbar puncture; and subject with a positive cerebrospinal fluid (CSF) for AML blasts is not eligible.
  • 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 the start of study drug.
  • Subject has uncontrolled or significant cardiovascular disease - 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).
  • Subject has an active acute or chronic systemic fungal, bacterial, viral, or other infection.
  • Subject has a concurrent disease (e.g. a history of serious organ dysfunction or disease) that may place the subject at undue risk to undergo induction therapy per protocol, or that might obscure assessments of drug safety.
  • Subject requires treatment with concomitant drugs that prolong QT/QTc interval or strong cytochrome P-3A4 (CYP3A4) inhibitors or inducers with the exception of antibiotics, antifungals, and antivirals that are used as standard of care 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 is a female who is lactating.
  • 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): NCT01390337

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United States, Florida
Mayo Clinic Jacksonville
Jacksonville, Florida, United States, 32224
United States, Illinois
Northwestern University
Chicago, Illinois, United States, 60611
United States, Maryland
Johns Hopkins Medical Institute
Baltimore, Maryland, United States, 21231
United States, New York
Memorial-Sloan Kettering Cancer Center
New York, New York, United States, 10065
United States, Texas
M.D. Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
Daiichi Sankyo, Inc.
Ambit Biosciences Corporation
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Study Director: Guy Gammon, MB, BS, MRCP Medical Monitor, Ambit Biosciences Corporation
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Responsible Party: Daiichi Sankyo, Inc.
ClinicalTrials.gov Identifier: NCT01390337    
Other Study ID Numbers: 2689-CL-0005
First Posted: July 11, 2011    Key Record Dates
Last Update Posted: February 12, 2019
Last Verified: October 2015
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)
Clinical Study Report (CSR)
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.:
Acute Myeloid Leukemia (AML)
De Novo Acute Myeloid Leukemia (AML)
Newly diagnosed Acute Myeloid Leukemia (AML)
FMS-like tyrosine kinase (FLT3)
FMS-like tyrosine kinase (FLT3) Inhibitor
Kinase Inhibitor
Additional relevant MeSH terms:
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Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors