Phase 2 Open-label, Single-arm Study of Quizartinib (AC220) Monotherapy in Japanese Patients With FLT3-ITD Positive Refractory or Relapsed Acute Myeloid Leukemia

Daiichi Sankyo Co., Ltd.0 sites37 target enrollmentDecember 8, 2016

ConditionsLeukemia, Myeloid, Acute

InterventionsQuizartinib

DrugsQuizartinib

Overview

Phase: Phase 2
Intervention: Quizartinib
Conditions: Leukemia, Myeloid, Acute
Sponsor: Daiichi Sankyo Co., Ltd.
Enrollment: 37
Primary Endpoint: Composite Complete Remission (CRc) Rate After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML
Status: Completed
Last Updated: 6 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Similar Trials

Overview

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.

Registry

clinicaltrials.gov

Start Date

December 8, 2016

End Date

September 14, 2018

Last Updated

6 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Daiichi Sankyo Co., Ltd.

Responsible Party

Sponsor

Eligibility Criteria

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

Arms & Interventions

Initial dose 30 mg/day 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.

Intervention: Quizartinib

Initial dose 20 mg/day 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.

Intervention: Quizartinib

Outcomes

Primary Outcomes

Composite Complete Remission (CRc) Rate After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML

Time Frame: 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 Outcomes

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)
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)
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)
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)
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)
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)
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)