Phase 1 Study of Quizartinib

• Sponsor: Daiichi Sankyo Co., Ltd. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02675478
• Collaborator: (none)
• Enrollment: 17
• Location: 1
• Arm: 1
• Duration (Months): 33.4
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Relapsed AML; Refractory AML	Drug: AC220	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 17 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1, Open-Label, Dose Escalation Study of Quizartinib, An Oral FLT3 Inhibitor, in Japanese Patients With Relapsed or Refractory Acute Myeloid Leukemia
• Study Start Date: Feb 1, 2016
• Actual Primary Completion Date: Nov 13, 2018
• Actual Study Completion Date: Nov 13, 2018

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. number of subjects experiencing adverse events [first dose to follow-up, approximately 1 year]

2. Cmax of quizartinib and its active metabolite [Cycle 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.

3. Tmax of quizartinib and its active metabolite [Cycle 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.

4. AUCtau of quizartinib and its active metabolite [Cycle 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.

5. Cmax,ss of quizartinib and its active metabolite [Cycle 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.

6. Ctrough of quizartinib and its active metabolite [Cycle 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.

7. Tmax,ss of quizartinib and its active metabolite [Cycle 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.

8. AUCtau,ss of quizartinib and its active metabolite [Cycle 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

1. FMS-like tyrosine kinase-3 / internal tandem duplication FLT3/ITD allelic ratio [Cycle 1: Days 1, 2, 8, 15]

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

2. PIA assessment [Cycle 1: Days 1, 2, 8, 15]

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

3. bone marrow findings [Cycle 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.

4. absolute neutrophil count [Cycle 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.

5. platelet count [Cycle 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Tokyo		Japan

Sponsors and Collaborators

• Daiichi Sankyo Co., Ltd.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Daiichi Sankyo Co., Ltd.
• ClinicalTrials.gov Identifier: NCT02675478
• Other Study ID Numbers: AC220-A-J101
• First Posted: Feb 5, 2016
• Last Update Posted: Feb 12, 2019
• Last Verified: Nov 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Keywords provided by Daiichi Sankyo Co., Ltd.: AML; phase 1; oncology

Study Results

No Results Posted as of Feb 12, 2019