Phase 1 Study of Quizartinib

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

Official Title
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A Phase 1, Open-Label, Dose Escalation Study of Quizartinib, An Oral FLT3 Inhibitor, in Japanese Patients With Relapsed or Refractory Acute Myeloid Leukemia

Conditions
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Relapsed AML, Refractory AML

Intervention / Treatment
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* Drug: AC220


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AC220<br>This study will follow a mCRM (modified continual reassessment method) + EWOC (Escalation with Overdose Control) design. | Drug: AC220<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| number of subjects experiencing adverse events |  | first dose to follow-up, approximately 1 year | 
| Cmax of quizartinib and its active metabolite | Evaluate the pharmacokinetics of quizartinib and its active metabolite, AC886 by Cmax, Tmax, AUCtau, Cmax,ss, Ctrough, Tmax,ss, AUCtau,ss. | Cycle 1: Days 1, 2, 4, 8, 11, 15, 16, 18, 22, 28; Cycle 2 and on: Days 1, 15 | 
| Tmax of quizartinib and its active metabolite | Evaluate the pharmacokinetics of quizartinib and its active metabolite, AC886 by Cmax, Tmax, AUCtau, Cmax,ss, Ctrough, Tmax,ss, AUCtau,ss. | Cycle 1: Days 1, 2, 4, 8, 11, 15, 16, 18, 22, 28; Cycle 2 and on: Days 1, 15 | 
| AUCtau of quizartinib and its active metabolite | Evaluate the pharmacokinetics of quizartinib and its active metabolite, AC886 by Cmax, Tmax, AUCtau, Cmax,ss, Ctrough, Tmax,ss, AUCtau,ss. | Cycle 1: Days 1, 2, 4, 8, 11, 15, 16, 18, 22, 28; Cycle 2 and on: Days 1, 15 | 
| Cmax,ss of quizartinib and its active metabolite | Evaluate the pharmacokinetics of quizartinib and its active metabolite, AC886 by Cmax, Tmax, AUCtau, Cmax,ss, Ctrough, Tmax,ss, AUCtau,ss. | Cycle 1: Days 1, 2, 4, 8, 11, 15, 16, 18, 22, 28; Cycle 2 and on: Days 1, 15 | 
| Ctrough of quizartinib and its active metabolite | Evaluate the pharmacokinetics of quizartinib and its active metabolite, AC886 by Cmax, Tmax, AUCtau, Cmax,ss, Ctrough, Tmax,ss, AUCtau,ss. | Cycle 1: Days 1, 2, 4, 8, 11, 15, 16, 18, 22, 28; Cycle 2 and on: Days 1, 15 | 
| Tmax,ss of quizartinib and its active metabolite | Evaluate the pharmacokinetics of quizartinib and its active metabolite, AC886 by Cmax, Tmax, AUCtau, Cmax,ss, Ctrough, Tmax,ss, AUCtau,ss. | Cycle 1: Days 1, 2, 4, 8, 11, 15, 16, 18, 22, 28; Cycle 2 and on: Days 1, 15 | 
| AUCtau,ss of quizartinib and its active metabolite | Evaluate the pharmacokinetics of quizartinib and its active metabolite, AC886 by Cmax, Tmax, AUCtau, Cmax,ss, Ctrough, Tmax,ss, AUCtau,ss. | Cycle 1: Days 1, 2, 4, 8, 11, 15, 16, 18, 22, 28; Cycle 2 and on: Days 1, 15 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| FMS-like tyrosine kinase-3 / internal tandem duplication FLT3/ITD allelic ratio | Exploratory assessment of quizartinib-related biomarkers such as FLT3-ITD allelic ratio, PIA assessment. | Cycle 1: Days 1, 2, 8, 15 | 
| PIA assessment | Exploratory assessment of quizartinib-related biomarkers such as FLT3-ITD allelic ratio, PIA assessment. | Cycle 1: Days 1, 2, 8, 15 | 
| bone marrow findings | Exploratory analyses of tumor response to quizartinib based on bone marrow findings, absolute neutrophil count, and platelet count. | Cycle 1: Days 15, 28; Cycle 2 and on: Day 28 | 
| absolute neutrophil count | Exploratory analyses of tumor response to quizartinib based on bone marrow findings, absolute neutrophil count, and platelet count. | Cycle 1: Days 15, 28; Cycle 2 and on: Day 28 | 
| platelet count | Exploratory analyses of tumor response to quizartinib based on bone marrow findings, absolute neutrophil count, and platelet count. | Cycle 1: Days 15, 28; Cycle 2 and on: Day 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AML, phase 1, oncology