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

July 7, 2011
September 20, 2013
October 2011
March 2014   (final data collection date for primary outcome measure)
  • 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 ]
Same as current
Complete list of historical versions of study NCT01390337 on ClinicalTrials.gov Archive Site
Pharmacokinetic assessment through analysis of blood samples [ Time Frame: Up to Day 11 ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
A Study to Assess AC220 Given in Combination With Induction and Consolidation Therapy in Newly Diagnosed Acute Myeloid Leukemia (AML)
A Phase 1 Study of AC220 (ASP2689) in Combination With Induction and Consolidation Chemotherapy in Patients With Newly Diagnosed Acute Myeloid Leukemia

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.

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.

Interventional
Phase 1
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Leukemia, Myeloid, Acute
  • 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
Experimental: AC220
Interventions:
  • Drug: AC220
  • Drug: daunorubicin
  • Drug: cytarabine
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
58
September 2014
March 2014   (final data collection date for primary outcome measure)

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.
Both
18 Years to 60 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01390337
2689-CL-0005
No
Ambit Biosciences Corporation
Ambit Biosciences Corporation
Not Provided
Study Director: Guy Gammon, MB, BS, MRCP Medical Monitor, Ambit Biosciences Corporation
Ambit Biosciences Corporation
September 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP