Clinical trial NCT01565668: Open Label Study to Evaluate Safety and Efficacy of 2 Doses of Quizartinib in Patients With Relapsed or Refractory Acute Myeloid Leukemia
Official title: A Phase 2, Randomized, Open-Label Study of the Safety and Efficacy of Two Doses of Quizartinib (AC220; ASP2689) in Subjects With FLT3-ITD Positive Relapsed or Refractory Acute Myeloid Leukemia (AML)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Leukemia, Myeloid, Acute
Keywords: FLT3-ITD positive Acute Myeloid Leukemia (AML)
AC220
Relapse
Refractory
Lead sponsor: Daiichi Sankyo
Sponsor class: INDUSTRY
Collaborators: name: Ambit Biosciences Corporation
First posted: 2012-03-29
Enrollment: 76
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Number of Participants Who Achieved Composite Complete Response (CRc) (Intent-to-Treat Population)
timeFrame: At end of Cycle 2 (after two complete 28-day cycles post treatment)
Secondary outcomes:
measure: Number of Participants Who Achieved Complete Remission (CR) (Intent-to-Treat Population)
timeFrame: At end of treatment visit (approximately 3 years post treatment)
measure: Overall Survival (OS) After Approximately 3 Years (Intent-to-Treat Population)
timeFrame: Evaluated at end of study, up to 6 months (approximately 3 years post treatment)
measure: Event Free Survival (EFS) After Approximately 3 Years (Intent-to-Treat Population)
timeFrame: Evaluated at end of study, up to 6 months (approximately 3 years post treatment)
measure: Leukemia Free Survival (LFS) After Approximately 3 Years (Intent-to-Treat Population)
timeFrame: Evaluated at end of study, up to 6 months (approximately 3 years post treatment)
measure: Duration of Remission After Approximately 3 Years (Intent-to-Treat Population)
timeFrame: Evaluated at end of study, up to 6 months (approximately 3 years post treatment)
measure: Time to Composite Complete Remission (CRc) in Participants Who Achieved CRc After Approximately 3 Years (Intent-to-Treat Population)
timeFrame: Evaluated at end of study, up to 6 months (approximately 3 years post treatment)
measure: Percentage of Participants Undergoing Hematopoietic Stem Cell Transplantation (HSCT) After Approximately 3 Years (Intent-to-Treat Population)
timeFrame: Evaluated at end of study, up to 6 months (approximately 3 years post treatment)
measure: Percentage of Participants With Grade 2 or Higher QT Interval Corrected for Heart Rate Using Fridericia's Formula (QTcF) Prolongation After Receiving Quizartinib (Safety Analysis Set)
timeFrame: Evaluated at end of study, up to 6 months (approximately 3 years post treatment)
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA School of Medicine
state: California
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Baltimore
country: United States
facility: University of Maryland Greenebaum Cancer Center
state: Maryland
city: Baltimore
country: United States
facility: John Hopkins University
state: Maryland
city: Boston
country: United States
facility: Tufts University School of Medicine-Tufts Medical Center
state: Massachusetts
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
city: Hershey
country: United States
facility: Penn State Milton S. Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina, Hollings Cancer Center
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt University, Vanderbilt Ingram Cancer Center
state: Tennessee
city: Dallas
country: United States
facility: UT Southwestern Medical Center, Simmons Cancer Center
state: Texas
city: Houston
country: United States
facility: MD Anderson
state: Texas
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
city: Angers
country: France
facility: CHU d'Angers
city: Grenoble
country: France
facility: CHU de Grenoble
city: Paris
country: France
facility: Hôpital Saint Antoine
city: Pessac
country: France
facility: Hôpital Haut Lévêque
city: Bologna
country: Italy
facility: Universitaria Policlinico S. Orsola Malpighi, Institute of Hemtology "L. & A. Seragnoli"
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals
state: England
Study officials:
affiliation: Daiichi Sankyo
name: Global Clinical Leader
role: STUDY_DIRECTOR
References: