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

Sponsor

Daiichi Sankyo, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT01390337

Collaborator

Ambit Biosciences Corporation (Industry)

Enrollment

Locations

Arm

Duration (Months)

3.8

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

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

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 :

Oct 1, 2011

Actual Primary Completion Date :

Feb 1, 2015

Actual Study Completion Date :

Feb 1, 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

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

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 Outcome Measures

Pharmacokinetic assessment through analysis of blood samples [Up to Day 11]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

	Site	City	State	Country	Postal Code
1	Mayo Clinic Jacksonville	Jacksonville	Florida	United States	32224
2	Northwestern University	Chicago	Illinois	United States	60611
3	Johns Hopkins Medical Institute	Baltimore	Maryland	United States	21231
4	Memorial-Sloan Kettering Cancer Center	New York	New York	United States	10065
5	M.D. Anderson Cancer Center	Houston	Texas	United States	77030