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Phase 1 Study of Quizartinib

Phase 1
Completed
Conditions
Refractory AML
Relapsed AML
Interventions
Registration Number
NCT02675478
Lead Sponsor
Daiichi Sankyo Co., Ltd.
Brief Summary

This is a dose escalation study to evaluate the safety, tolerability, and pharmacokinetics of quizartinib for Japanese acute myeloid leukemia (AML) subjects.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
17
Inclusion Criteria
  • Relapsed or refractory AML
  • AML for which no standard treatment is available
  • ECOG Performance Status (PS) of 0 to 2
Exclusion Criteria
  • Acute Promyelocytic Leukemia
  • chronic myelogenous leukemia in blast phase (BCR-ABL fusion gene positive)
  • History of other malignancies within 3 years prior to enrollment, except curatively treated in-situ carcinoma, AML, or MDS.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
AC220AC220This study will follow a mCRM (modified continual reassessment method) + EWOC (Escalation with Overdose Control) design.
Primary Outcome Measures
NameTimeMethod
Cmax,ss of quizartinib and its active metaboliteCycle 1: Days 1, 2, 4, 8, 11, 15, 16, 18, 22, 28; Cycle 2 and on: Days 1, 15

Evaluate the pharmacokinetics of quizartinib and its active metabolite, AC886 by Cmax, Tmax, AUCtau, Cmax,ss, Ctrough, Tmax,ss, AUCtau,ss.

AUCtau,ss of quizartinib and its active metaboliteCycle 1: Days 1, 2, 4, 8, 11, 15, 16, 18, 22, 28; Cycle 2 and on: Days 1, 15

Evaluate the pharmacokinetics of quizartinib and its active metabolite, AC886 by Cmax, Tmax, AUCtau, Cmax,ss, Ctrough, Tmax,ss, AUCtau,ss.

number of subjects experiencing adverse eventsfirst dose to follow-up, approximately 1 year
Cmax of quizartinib and its active metaboliteCycle 1: Days 1, 2, 4, 8, 11, 15, 16, 18, 22, 28; Cycle 2 and on: Days 1, 15

Evaluate the pharmacokinetics of quizartinib and its active metabolite, AC886 by Cmax, Tmax, AUCtau, Cmax,ss, Ctrough, Tmax,ss, AUCtau,ss.

Tmax of quizartinib and its active metaboliteCycle 1: Days 1, 2, 4, 8, 11, 15, 16, 18, 22, 28; Cycle 2 and on: Days 1, 15

Evaluate the pharmacokinetics of quizartinib and its active metabolite, AC886 by Cmax, Tmax, AUCtau, Cmax,ss, Ctrough, Tmax,ss, AUCtau,ss.

Ctrough of quizartinib and its active metaboliteCycle 1: Days 1, 2, 4, 8, 11, 15, 16, 18, 22, 28; Cycle 2 and on: Days 1, 15

Evaluate the pharmacokinetics of quizartinib and its active metabolite, AC886 by Cmax, Tmax, AUCtau, Cmax,ss, Ctrough, Tmax,ss, AUCtau,ss.

Tmax,ss of quizartinib and its active metaboliteCycle 1: Days 1, 2, 4, 8, 11, 15, 16, 18, 22, 28; Cycle 2 and on: Days 1, 15

Evaluate the pharmacokinetics of quizartinib and its active metabolite, AC886 by Cmax, Tmax, AUCtau, Cmax,ss, Ctrough, Tmax,ss, AUCtau,ss.

AUCtau of quizartinib and its active metaboliteCycle 1: Days 1, 2, 4, 8, 11, 15, 16, 18, 22, 28; Cycle 2 and on: Days 1, 15

Evaluate the pharmacokinetics of quizartinib and its active metabolite, AC886 by Cmax, Tmax, AUCtau, Cmax,ss, Ctrough, Tmax,ss, AUCtau,ss.

Secondary Outcome Measures
NameTimeMethod
bone marrow findingsCycle 1: Days 15, 28; Cycle 2 and on: Day 28

Exploratory analyses of tumor response to quizartinib based on bone marrow findings, absolute neutrophil count, and platelet count.

FMS-like tyrosine kinase-3 / internal tandem duplication FLT3/ITD allelic ratioCycle 1: Days 1, 2, 8, 15

Exploratory assessment of quizartinib-related biomarkers such as FLT3-ITD allelic ratio, PIA assessment.

PIA assessmentCycle 1: Days 1, 2, 8, 15

Exploratory assessment of quizartinib-related biomarkers such as FLT3-ITD allelic ratio, PIA assessment.

absolute neutrophil countCycle 1: Days 15, 28; Cycle 2 and on: Day 28

Exploratory analyses of tumor response to quizartinib based on bone marrow findings, absolute neutrophil count, and platelet count.

platelet countCycle 1: Days 15, 28; Cycle 2 and on: Day 28

Exploratory analyses of tumor response to quizartinib based on bone marrow findings, absolute neutrophil count, and platelet count.

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