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

Daiichi Sankyo Co., Ltd.37 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Leukemia, Myeloid, Acute

Interventions

QuizartinibDRUG

Quizartinib was orally administered once daily every morning. Treatment with quizartinib was administered in 28-day cycles and continued until the discontinuation criteria for treatment were met.

Eligibility

Sex: ALLMin age: 20 Years

Medical Language ↔ Plain English

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

Locations (27)

Unnamed facility

Aichi, Japan

Unnamed facility

Akita, Japan

Unnamed facility

Chiba, Japan

Outcomes

Primary Outcomes

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

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.

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

Secondary Outcomes

Best Response After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory 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).

Time frame: 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

Response 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 until the end of treatment, except for responses from any subsequent AML

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

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.

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

Data from ClinicalTrials.gov

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Unnamed facility

Fukui, Japan

Unnamed facility

Fukuoka, Japan

Unnamed facility

Fukushima, Japan

Unnamed facility

Gifu, Japan

Unnamed facility

Gunma, Japan

Unnamed facility

Hiroshima, Japan

Unnamed facility

Hokkaido, Japan

...and 17 more locations

Overall Survival (OS) After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML

OS is defined as the time from registration (enrollment) until death from any cause.

Time frame: 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

Event-free Survival (EFS) After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML

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.

Time frame: 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

Leukemia-free Survival (LFS) After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML

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.

Time frame: 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

Hematopoietic Stem Cell Transplantation Rate After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML

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.

Time frame: 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

Time frame: Cycle 1, Days 1 and 15; Cycle 2, Day 1

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

Time frame: Cycle 1, Days 1 and 15; Cycle 2, Day 1

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

Time frame: Cycle 1, Day 15

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

Time frame: Cycle 1, Days 1 and 15; Cycle 2, Day 1