Phase 2 Study of Quizartinib in Participants With Acute Myeloid Leukemia (AML) FLT3 Internal Tandem Duplication (FLT3/ITD) Mutation

Phase 2

Completed

• Conditions: Leukemia, Myeloid, Acute
• Interventions: Drug: Quizartinib

• Registration Number: NCT02984995
• Lead Sponsor: Daiichi Sankyo Co., Ltd.

Brief Summary

This is a Phase 2, multi-center, open-label study to evaluate the efficacy, safety and pharmacokinetics of quizartinib monotherapy in Japanese subjects with FLT3-ITD positive refractory or relapsed acute myeloid leukemia.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2016-12-05
• Study First Submitted QC: 2016-12-05
• Study First Posted: 2016-12-07
• Study Start: 2016-12-08
• Primary Completion: 2018-03-28
• Study Completion: 2018-09-14
• Disposition First Submitted: 2019-03-13
• Disposition First Submitted QC: 2019-03-13
• Disposition First Posted: 2019-03-18
• Results First Submitted: 2019-09-25
• Status Verified: 2020-02
• Results First Submitted QC: 2020-02-04
• Last Update Submitted: 2020-02-04
• Results First Posted: 2020-02-17
• Last Update Posted: 2020-02-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 37

Inclusion Criteria

• AML patients in first relapse or refractory after all prior therapy
• Presence of the FLT3-ITD activating mutation in bone marrow or peripheral blood
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 to 2

Exclusion Criteria

• Diagnosis of acute promyelocytic leukemia
• AML secondary to prior chemotherapy for other neoplasms.
• Persistent, clinically significant > Grade 1 non-hematologic toxicity from prior AML therapy
• Prior treatment with a FLT3 targeted therapy
• Active infection not well controlled by antibacterial, antifungal and/or antiviral therapy

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Initial dose 30 mg/day quizartinib	Quizartinib	Participants who received an initial dose of 30 mg/day of quizartinib and, if no QT prolongation, the dose escalated to 60 mg/day at Day 15.
Initial dose 20 mg/day quizartinib	Quizartinib	Participants who received a CYP3A4 strong inhibitor received an initial dose of 20 mg/day of quizartinib and, if no QT prolongation, the dose escalated to 30 mg/day at Day 15.

Primary Outcome Measures

Name	Time	Method
Composite Complete Remission (CRc) Rate After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML	Baseline, cycle 2 day 1, cycle 3 day 1, cycle 4 day 1 up until the end of treatment, except for responses from any subsequent AML therapy including transplantation	The composite complete remission (CRc) rate is defined as the proportion of participants whose best response is complete remission \[CR\], CR with incomplete platelet recovery \[CRp\], or CR with incomplete hematological recovery \[CRi\]) after treatment with quizartinib.

Secondary Outcome Measures

Name	Time	Method
Response Rate After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML	Baseline, cycle 2 day 1, cycle 3 day 1, cycle 4 day 1 until the end of treatment, except for responses from any subsequent AML
Best Response After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML	Baseline, cycle 2 day 1, cycle 3 day 1, cycle 4 day 1 until the end of treatment, except for responses from any subsequent AML	Best response is defined as the best measured response over all response assessments (complete response \[CR\], CR with incomplete platelet recovery \[CRp\], CR with incomplete hematological recovery \[CRi\], partial remission \[PR\], no response \[NR\], or Unknown) at all time points after the first dose of the study drug to the end of treatment (does not include response from any subsequent AML therapy including transplantation).
Change in the Trough Plasma Concentration (Ctrough) of Quizartinib and Its Metabolite (AC886) After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML	Cycle 1, Day 15
Change in the Maximum Plasma Concentration (Cmax) of Quizartinib and Its Metabolite (AC886) After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML	Cycle 1, Days 1 and 15; Cycle 2, Day 1
Duration of Composite Complete Remission (CRc) After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML	Baseline, cycle 2 day 1, cycle 3 day 1, cycle 4 day 1 up until the end of treatment, except for responses from any subsequent AML therapy including transplantation	Duration from the date of first composite complete remission (CRc) (complete remission \[CR\], CR with incomplete platelet recovery \[CRp\], or CR with incomplete hematological recovery \[CRi\]) observed to the date of documented relapse was assessed.
Leukemia-free Survival (LFS) After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML	Baseline, cycle 2 day 1, cycle 3 day 1, cycle 4 day 1 until the end of treatment, except for responses from any subsequent AML therapy including transplantation up to 28 weeks	Leukemia-free survival (LFS) is the time from the first documented response of CRc until documented relapse or death from any cause. The analysis for LFS will be conditional on the participant having a documented best response of CRc.
Overall Survival (OS) After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML	Baseline, cycle 2 day 1, cycle 3 day 1, cycle 4 day 1 until the end of treatment, except for responses from any subsequent AML therapy including transplantation up to 1 year	OS is defined as the time from registration (enrollment) until death from any cause.
Hematopoietic Stem Cell Transplantation Rate After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML	Up to new AML treatment or 1 year post treatment	Proportion of participants who start hematopoietic stem cell transplantation (HSCT) immediately after the end of treatment with the study drug without receiving other treatment for AML, except for conditioning regiment for HSCT, was assessed.
Change in the Area Under the Plasma Concentration Time Curve (AUC) of Quizartinib and Its Active Metabolite After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML	Cycle 1, Days 1 and 15; Cycle 2, Day 1
Event-free Survival (EFS) After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML	Baseline, cycle 2 day 1, cycle 3 day 1, cycle 4 day 1 until the end of treatment, except for responses from any subsequent AML therapy including transplantation up to 32 weeks	Event-free survival is defined as the time from date of registration until documented refractory disease, relapse after response of composite complete remission (CRc = complete remission \[CR\], CR with incomplete platelet recovery \[CRp\], or CR with incomplete hematological recovery \[CRi\]), or death from any cause, whichever occurs first.
Change in the Time to Reach Maximum Plasma Concentration (Tmax) of Quizartinib and Its Metabolite (AC886) After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML	Cycle 1, Days 1 and 15; Cycle 2, Day 1