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

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

Study Description

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.

Study Design

• 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

Arms and Interventions

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

Outcome Measures

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 ]

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

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

Investigators

• Study Director: Guy Gammon, MB, BS, MRCP; Medical Monitor, Ambit Biosciences Corporation

More Information

• Responsible Party: Daiichi Sankyo, Inc.
• ClinicalTrials.gov Identifier: NCT01390337
• Other Study ID Numbers: 2689-CL-0005
• First Posted: July 11, 2011
• 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.:

AC220; 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; Kinase Inhibitor; Pharmacokinetics; ASP2689; quizartinib

Additional relevant MeSH terms:

Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Neoplasms by Histologic Type; Neoplasms; Cytarabine; Daunorubicin; Antimetabolites, Antineoplastic; Antimetabolites; 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