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

Daiichi Sankyo

Status and phase

Completed

Phase 2

Conditions

Leukemia, Myeloid, Acute

Treatments

Drug: AC220

Study type

Interventional

Funder types

Industry

Identifiers

NCT01565668

2689-CL-2004

2011-005408-13 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment

76 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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