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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Ambit Biosciences Corporation
ClinicalTrials.gov Identifier:
NCT01390337
First received: July 7, 2011
Last updated: September 20, 2013
Last verified: September 2013
  Purpose

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 Intervention Phase
Leukemia, Myeloid, Acute
Drug: AC220
Drug: daunorubicin
Drug: cytarabine
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Ambit Biosciences Corporation:

Primary Outcome Measures:
  • Safety assessed by recording adverse events, physical examinations, vital signs, electrocardiograms (ECGs), and laboratory assessments [ Time Frame: up to Day 42 ] [ Designated as safety issue: No ]
  • Incidence of Dose Limiting Toxicity (DLT) [ Time Frame: up to Day 42 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Pharmacokinetic assessment through analysis of blood samples [ Time Frame: Up to Day 11 ] [ Designated as safety issue: No ]

Estimated Enrollment: 58
Study Start Date: October 2011
Estimated Study Completion Date: September 2014
Estimated Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
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
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: NCT01390337

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
Ambit Biosciences Corporation
Investigators
Study Director: Guy Gammon, MB, BS, MRCP Medical Monitor, Ambit Biosciences Corporation
  More Information

No publications provided

Responsible Party: Ambit Biosciences Corporation
ClinicalTrials.gov Identifier: NCT01390337     History of Changes
Other Study ID Numbers: 2689-CL-0005
Study First Received: July 7, 2011
Last Updated: September 20, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Ambit Biosciences Corporation:
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, Myeloid
Leukemia, Myeloid, Acute
Leukemia
Neoplasms by Histologic Type
Neoplasms
Cytarabine
Daunorubicin
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on September 16, 2014