Open Label Study to Evaluate Safety and Efficacy of 2 Doses of Quizartinib in Patients With Relapsed or Refractory Acute Myeloid Leukemia

NCT ID: NCT01565668

Last Updated: 2019-12-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 76 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-04-30
• Study Completion Date: 2015-03-31

Brief Summary

This study will evaluate two doses of Quizartinib in patients with relapsed or refractory acute myeloid leukemia who are also FMS-like tyrosine kinase - internal tandem duplication ( FLT3-ITD) positive. Patient will be randomly assigned in a 1:1 ratio to one of two treatment arms. Both treatment arms will receive Quizartinib but at different doses. The study treatment is taken orally in 28 day cycles until either disease progression occurs or an unacceptable toxicity occurs. In addition to the study assessments to evaluate the disease, blood will be drawn to measure drug levels and biomarkers. Patients will be followed for survival at three month intervals after the end of treatment.

Conditions

Leukemia, Myeloid, Acute

Keywords

FLT3-ITD positive Acute Myeloid Leukemia (AML); AC220; Relapse; Refractory

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

AC220 Dose Level 1

Group Type: EXPERIMENTAL

AC220

Intervention Type: DRUG

oral

AC220 Dose Level 2

Group Type: EXPERIMENTAL

AC220

Intervention Type: DRUG

oral

Interventions

AC220

oral

Intervention Type: DRUG

Other Intervention Names

Quizartinib; ASP2689

Eligibility Criteria

Inclusion Criteria

• Subject has morphologically documented primary acute myeloid leukemia (AML) or AML secondary to myelodysplastic syndrome (MDS) as defined by the World Health Organization (WHO) criteria, as determined by pathology review at the treating institution and has relapsed or is refractory after 1 second line (salvage) regimen or after hematopoietic stem cell transplantation (HSCT)
• Subject is positive for FLT3-ITD activating mutation in bone marrow or peripheral blood (>10% allelic ratio)
• Eastern Cooperative Oncology Group performance status of 0 to 2
• In the absence of rapidly progressing disease clearly documented by the investigator, the interval from prior treatment to time of AC220 administration will be at least 2 weeks (14 days) for prior cytotoxic agents or at least 5 half-lives for prior noncytotoxic agents, including immunosuppressive therapy post HSCT
• Persistent chronic clinically significant nonhematological toxicities from prior treatment (including chemotherapy, kinase inhibitors, immunotherapy, experimental agents, radiation, HSCT, or surgery) must be Grade ≤ 1
• Patients - both males and females - with reproductive potential are eligible

Exclusion Criteria

• Subject received previous treatment with AC220
• Subject has a diagnosis of acute promyelocytic leukemia
• Subject has a diagnosis of chronic myelogenous leukemia (CML) in blast crisis
• Subject has AML or antecedent MDS secondary to prior chemotherapy
• Subject has had HSCT and has either of the following:
• Donor lymphocyte infusion (DLI) is not permitted during the study or < 30 days prior to study entry
• Subject has clinically active central nervous system (CNS) leukemia. A subject is considered eligible if CNS leukemia is controlled and subject is receiving intrathecal (IT) therapy at study entry. Subjects should continue to receive IT therapy (or cranial radiation) as clinically indicated
• Subject has received concurrent chemotherapy, immunotherapy, or radiotherapy within 14 days prior to the first dose of AC220, or any ancillary therapy that is considered to be investigational (i.e., used for non-approved indications(s) and in the context of a research investigation) within 30 days or 5 half-lives (whichever is longer) prior to the first dose of study drug
• Subject requires treatment with concomitant drugs that prolong QT/QTc interval or with strong inhibitors or inducers of cytochrome P450- isozyme3A4 (CYP3A4) with the exception of antibiotics, antifungals, and antivirals that are used as standard of care post-transplant or 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 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 first dose of AC220
• Subject has uncontrolled or significant cardiovascular disease, including
• 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 not related to AML)
• Subject has an active uncontrolled acute or chronic systemic fungal, bacterial, viral, or other infection
• Subject has any of the following laboratory values:
• Subject is a female with a positive pregnancy test, pregnant, or breastfeeding
• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ambit Biosciences Corporation

INDUSTRY

Sponsor Role: collaborator

Daiichi Sankyo

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Global Clinical Leader

Role: STUDY_DIRECTOR

Daiichi Sankyo

Locations

UCLA School of Medicine

Los Angeles, California, United States

Northwestern University

Chicago, Illinois, United States

University of Chicago

Chicago, Illinois, United States

University of Maryland Greenebaum Cancer Center

Baltimore, Maryland, United States

John Hopkins University

Baltimore, Maryland, United States

Tufts University School of Medicine-Tufts Medical Center

Boston, Massachusetts, United States

University of Minnesota

Minneapolis, Minnesota, United States

Mayo Clinic

Rochester, Minnesota, United States

Hackensack University Medical Center

Hackensack, New Jersey, United States

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Weill Cornell Medical College

New York, New York, United States

Penn State Milton S. Hershey Medical Center

Hershey, Pennsylvania, United States

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

Medical University of South Carolina, Hollings Cancer Center

Charleston, South Carolina, United States

Vanderbilt University, Vanderbilt Ingram Cancer Center

Nashville, Tennessee, United States

UT Southwestern Medical Center, Simmons Cancer Center

Dallas, Texas, United States

MD Anderson

Houston, Texas, United States

Fred Hutchinson Cancer Research Center

Seattle, Washington, United States

CHU d'Angers

Angers, , France

CHU de Grenoble

Grenoble, , France

Hôpital Saint Antoine

Paris, , France

Hôpital Haut Lévêque

Pessac, , France

Universitaria Policlinico S. Orsola Malpighi, Institute of Hemtology "L. & A. Seragnoli"

Bologna, , Italy

Nottingham University Hospitals

Nottingham, England, United Kingdom

Countries

United States; France; Italy; United Kingdom

Other Identifiers

2011-005408-13

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2689-CL-2004

Identifier Type: -

Identifier Source: org_study_id