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

NCT01390337 | Completed Phase 1

• 1 other identifier: 2689-CL-0005
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 5

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.

Conditions

Leukemia, Myeloid, Acute

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Safety assessed by recording adverse events, physical examinations, vital signs, electrocardiograms (ECGs), and laboratory assessments

  up to Day 42

• Incidence of Dose Limiting Toxicity (DLT)

  up to Day 42

Secondary Outcomes (1)

• Pharmacokinetic assessment through analysis of blood samples

  Up to Day 11

Study Arms (1)

AC220

EXPERIMENTAL

Drug: AC220; Drug: daunorubicin; Drug: cytarabine

Interventions

AC220 DRUG

Oral Liquid

Also known as: quizartinib, ASP2689

AC220

daunorubicin DRUG

Intravenous Infusion

Also known as: Cerubidine, daunorubicin hydrochloride

AC220

cytarabine DRUG

Intravenous Infusion

Also known as: Ara-C, Cytarabine Hydrochloride, Cytosar, Cytosine, Arabinoside

AC220

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Daiichi Sankyo: lead
• Ambit Biosciences Corporation: collaborator

Study Sites (5)

Mayo Clinic Jacksonville

Jacksonville, Florida, 32224, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Johns Hopkins Medical Institute

Baltimore, Maryland, 21231, United States

Location

Memorial-Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

M.D. Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

quizartinib; Daunorubicin; Cytarabine; Cytosine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Pyrimidinones

Study Officials

• Guy Gammon, MB, BS, MRCP

  Medical Monitor, Ambit Biosciences Corporation

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 7, 2011
• First Posted: July 11, 2011
• Study Start: October 1, 2011
• Primary Completion: February 1, 2015
• Study Completion: February 1, 2015
• Last Updated: February 12, 2019

Record last verified: 2015-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, 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.

Locations

US (5)