Leukemia, Myeloid, Acute
Conditions
Keywords
FLT3-ITD, Positive refractory or relapsed acute myeloid leukemia, Hematology malignancy, Developmental Phase II
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.
Interventions
DRUGQuizartinib
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.
Sponsors
Daiichi Sankyo
Daiichi Sankyo Co., Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
| 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. |
| 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. |
| 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. |
| 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. |
| 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 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 | — |
| 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 | — |
| 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 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 | — |
| 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 | — |
Countries
Japan
Participant flow
Recruitment details
A total of 37 participants who met all inclusion and no exclusion criteria were enrolled in the study.
Pre-assignment details
Quizartinib initial dose was 30 mg/day and escalated to 60 mg/day. For subjects receiving strong cytochrome P450 (CYP) 3A4 inhibitors, the initial dose was 20 mg/day. An increase from the initial dose of 30 mg/day to 60 mg/day or 20 mg/day to 30 mg/day was determined on Day 16 of Cycle 1 and Day 1 of Cycle 2 based on dose increase criteria.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 34 |
| 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. | 3 |
| Total | 37 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Progressive disease | 11 | 1 |
| Overall Study | Required stem cell transplant | 13 | 2 |
Baseline characteristics
| Characteristic | Total | Initial Dose 20 mg/Day Quizartinib | Initial Dose 30 mg/Day Quizartinib |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 20 Participants | 1 Participants | 19 Participants |
| Age, Categorical Between 18 and 65 years | 17 Participants | 2 Participants | 15 Participants |
| Age, Continuous | 60.0 years STANDARD_DEVIATION 14.68 | 58.0 years STANDARD_DEVIATION 9.92 | 60.2 years STANDARD_DEVIATION 14.51 |
| BMI | 20.84 kg/m^2 STANDARD_DEVIATION 2.58 | 22.25 kg/m^2 STANDARD_DEVIATION 3.37 | 20.72 kg/m^2 STANDARD_DEVIATION 2.53 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 37 Participants | 3 Participants | 34 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| FLT3-ITD Status Negative | 5 Participants | 0 Participants | 5 Participants |
| FLT3-ITD Status Positive | 32 Participants | 3 Participants | 29 Participants |
| Region of Enrollment Japan | 37 participants | 3 participants | 34 participants |
| Response to Prior Therapy Refractory | 13 Participants | 0 Participants | 13 Participants |
| Response to Prior Therapy Relapse | 24 Participants | 3 Participants | 21 Participants |
| Sex: Female, Male Female | 22 Participants | 0 Participants | 22 Participants |
| Sex: Female, Male Male | 15 Participants | 3 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 13 / 34 | 1 / 3 | 14 / 37 |
| other Total, other adverse events | 34 / 34 | 3 / 3 | 37 / 37 |
| serious Total, serious adverse events | 14 / 34 | 3 / 3 | 17 / 37 |
Outcome results
Primary
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
Population: All participants with FLT3-ITD positive relapsed or refractory AML who achieved CR, CRp, or CRi, discontinued the study treatment, or completed response assessment at Cycle 4 Day 1.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Initial Dose 30 mg/Day Quizartinib | Composite Complete Remission (CRc) Rate After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML | 56.5 percentage of participants |
| Initial Dose 20 mg/Day Quizartinib | Composite Complete Remission (CRc) Rate After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML | 33.3 percentage of participants |
| Total | Composite Complete Remission (CRc) Rate After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML | 53.8 percentage of participants |
Secondary
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
Population: All participants with FLT3-ITD positive relapsed or refractory AML who achieved CR, CRp, CRi, or PR, discontinued the study treatment, or completed response assessment at Cycle 4 Day 1.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Initial Dose 30 mg/Day Quizartinib | Best Response After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML | Partial remission (PR) | 6 Participants |
| Initial Dose 30 mg/Day Quizartinib | Best Response After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML | Complete response with incomplete hematologic(CRi) | 12 Participants |
| Initial Dose 30 mg/Day Quizartinib | Best Response After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML | Complete response (CR) | 0 Participants |
| Initial Dose 30 mg/Day Quizartinib | Best Response After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML | Complete response with incomplete platelet (CRp) | 1 Participants |
| Initial Dose 30 mg/Day Quizartinib | Best Response After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML | No response (NR) | 5 Participants |
| Initial Dose 20 mg/Day Quizartinib | Best Response After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML | Complete response with incomplete hematologic(CRi) | 1 Participants |
| Initial Dose 20 mg/Day Quizartinib | Best Response After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML | Complete response (CR) | 0 Participants |
| Initial Dose 20 mg/Day Quizartinib | Best Response After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML | Complete response with incomplete platelet (CRp) | 0 Participants |
| Initial Dose 20 mg/Day Quizartinib | Best Response After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML | Partial remission (PR) | 1 Participants |
| Initial Dose 20 mg/Day Quizartinib | Best Response After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML | No response (NR) | 1 Participants |
| Total | Best Response After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML | No response (NR) | 6 Participants |
| Total | Best Response After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML | Partial remission (PR) | 7 Participants |
| Total | Best Response After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML | Complete response (CR) | 0 Participants |
| Total | Best Response After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML | Complete response with incomplete hematologic(CRi) | 13 Participants |
| Total | Best Response After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML | Complete response with incomplete platelet (CRp) | 1 Participants |
Secondary
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
Population: Pharmacokinetic (PK) parameters were assessed in the PK Analysis Set.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Initial Dose 30 mg/Day Quizartinib | 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, Day 1; Quizartinib (n=3,34,0,0) | 877 ng*h/mL | Standard Deviation 489 |
| Initial Dose 30 mg/Day Quizartinib | 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, Day 1; Active Metabolite (n=3,34,0,0) | 75.1 ng*h/mL | Standard Deviation 80.6 |
| Initial Dose 30 mg/Day Quizartinib | 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, Day 15; Quizartinib (n=3,32,0,0) | 2610 ng*h/mL | Standard Deviation 693 |
| Initial Dose 30 mg/Day Quizartinib | 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, Day 15; Active Metabolite (n=3,32,0,0) | 430 ng*h/mL | Standard Deviation 276 |
| Initial Dose 20 mg/Day Quizartinib | 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, Day 15; Quizartinib (n=3,32,0,0) | 3970 ng*h/mL | Standard Deviation 2610 |
| Initial Dose 20 mg/Day Quizartinib | 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, Day 1; Quizartinib (n=3,34,0,0) | 1170 ng*h/mL | Standard Deviation 716 |
| Initial Dose 20 mg/Day Quizartinib | 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, Day 1; Active Metabolite (n=3,34,0,0) | 560 ng*h/mL | Standard Deviation 391 |
| Initial Dose 20 mg/Day Quizartinib | 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, Day 15; Active Metabolite (n=3,32,0,0) | 3120 ng*h/mL | Standard Deviation 1300 |
| Total | 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 2, Day 1; Quizartinib (n=0,0,2,21) | 2960 ng*h/mL | Standard Deviation 749 |
| Total | 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 2, Day 1; Active Metabolite (n=0,0,2,21) | 983 ng*h/mL | Standard Deviation 389 |
| Quizartinib 60 mg/Day (With No Use of Strong CYP3A4 Inhibitor) | 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 2, Day 1; Quizartinib (n=0,0,2,21) | 9240 ng*h/mL | Standard Deviation 6090 |
| Quizartinib 60 mg/Day (With No Use of Strong CYP3A4 Inhibitor) | 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 2, Day 1; Active Metabolite (n=0,0,2,21) | 6530 ng*h/mL | Standard Deviation 2630 |
Secondary
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
Population: Pharmacokinetic (PK) parameters were assessed in the PK Analysis Set.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Initial Dose 30 mg/Day Quizartinib | 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, Day 1; Quizartinib (n=3,34,0,0) | 48.1 ng/mL | Standard Deviation 25.9 |
| Initial Dose 30 mg/Day Quizartinib | 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, Day 1; Active Metabolite (n=3,34,0,0) | 3.92 ng/mL | Standard Deviation 4.49 |
| Initial Dose 30 mg/Day Quizartinib | 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, Day 15; Quizartinib (n=3,32,0,0) | 127 ng/mL | Standard Deviation 35.9 |
| Initial Dose 30 mg/Day Quizartinib | 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, Day 15; Active Metabolite (n=3,32,0,0) | 18.9 ng/mL | Standard Deviation 12.1 |
| Initial Dose 20 mg/Day Quizartinib | 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, Day 15; Quizartinib (n=3,32,0,0) | 211 ng/mL | Standard Deviation 132 |
| Initial Dose 20 mg/Day Quizartinib | 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, Day 1; Quizartinib (n=3,34,0,0) | 76.9 ng/mL | Standard Deviation 46.8 |
| Initial Dose 20 mg/Day Quizartinib | 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, Day 1; Active Metabolite (n=3,34,0,0) | 29.1 ng/mL | Standard Deviation 20.9 |
| Initial Dose 20 mg/Day Quizartinib | 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, Day 15; Active Metabolite (n=3,32,0,0) | 146 ng/mL | Standard Deviation 60.4 |
| Total | 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 2, Day 1; Quizartinib (n=0,0,2,21) | 149 ng/mL | Standard Deviation 38.2 |
| Total | 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 2, Day 1; Active Metabolite (n=0,0,2,21) | 43.7 ng/mL | Standard Deviation 17.7 |
| Quizartinib 60 mg/Day (With No Use of Strong CYP3A4 Inhibitor) | 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 2, Day 1; Quizartinib (n=0,0,2,21) | 480 ng/mL | Standard Deviation 296 |
| Quizartinib 60 mg/Day (With No Use of Strong CYP3A4 Inhibitor) | 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 2, Day 1; Active Metabolite (n=0,0,2,21) | 298 ng/mL | Standard Deviation 118 |
Secondary
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
Population: Pharmacokinetic (PK) parameters were assessed in the PK Analysis Set.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Initial Dose 30 mg/Day Quizartinib | 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, Day 1; Quizartinib (n=3,34,0,0) | 4.08 h |
| Initial Dose 30 mg/Day Quizartinib | 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, Day 1; Active Metabolite (n=2,33,0,0) | 24.33 h |
| Initial Dose 30 mg/Day Quizartinib | 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, Day 15; Quizartinib (n=3,32,0,0) | 4.08 h |
| Initial Dose 30 mg/Day Quizartinib | 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, Day 15; Active Metabolite (n=3,32,0,0) | 4.08 h |
| Initial Dose 20 mg/Day Quizartinib | 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, Day 15; Quizartinib (n=3,32,0,0) | 3.06 h |
| Initial Dose 20 mg/Day Quizartinib | 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, Day 1; Quizartinib (n=3,34,0,0) | 4.03 h |
| Initial Dose 20 mg/Day Quizartinib | 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, Day 1; Active Metabolite (n=2,33,0,0) | 24.32 h |
| Initial Dose 20 mg/Day Quizartinib | 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, Day 15; Active Metabolite (n=3,32,0,0) | 5.82 h |
| Total | 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 2, Day 1; Quizartinib (n=0,0,2,21) | 6.17 h |
| Total | 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 2, Day 1; Active Metabolite (n=0,0,2,21) | 14.17 h |
| Quizartinib 60 mg/Day (With No Use of Strong CYP3A4 Inhibitor) | 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 2, Day 1; Quizartinib (n=0,0,2,21) | 3.87 h |
| Quizartinib 60 mg/Day (With No Use of Strong CYP3A4 Inhibitor) | 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 2, Day 1; Active Metabolite (n=0,0,2,21) | 5.65 h |
Secondary
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
Population: Pharmacokinetic (PK) parameters were assessed in the PK Analysis Set.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Initial Dose 30 mg/Day Quizartinib | 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; Quizartinib | 98.2 ng/mL | Standard Deviation 19.7 |
| Initial Dose 30 mg/Day Quizartinib | 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; Active Metabolite | 17.8 ng/mL | Standard Deviation 11.3 |
| Initial Dose 20 mg/Day Quizartinib | 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; Quizartinib | 128 ng/mL | Standard Deviation 92.5 |
| Initial Dose 20 mg/Day Quizartinib | 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; Active Metabolite | 112 ng/mL | Standard Deviation 47.9 |
Secondary
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
Population: All participants with FLT3-ITD positive relapsed or refractory AML who had a documented best response of CRc.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Initial Dose 30 mg/Day Quizartinib | Duration of Composite Complete Remission (CRc) After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML | 16.1 weeks |
| Initial Dose 20 mg/Day Quizartinib | Duration of Composite Complete Remission (CRc) After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML | NA weeks |
| Total | Duration of Composite Complete Remission (CRc) After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML | 16.1 weeks |
Secondary
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
Population: All participants with FLT3-ITD positive relapsed or refractory AML.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Initial Dose 30 mg/Day Quizartinib | Event-free Survival (EFS) After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML | 12.7 weeks |
| Initial Dose 20 mg/Day Quizartinib | Event-free Survival (EFS) After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML | 0.1 weeks |
| Total | Event-free Survival (EFS) After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML | 12.7 weeks |
Secondary
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
Population: All participants with FLT3-ITD positive relapsed or refractory AML who underwent HSCT after treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Initial Dose 30 mg/Day Quizartinib | Hematopoietic Stem Cell Transplantation Rate After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML | 37.9 Percentage of participants |
| Initial Dose 20 mg/Day Quizartinib | Hematopoietic Stem Cell Transplantation Rate After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML | 33.3 Percentage of participants |
| Total | Hematopoietic Stem Cell Transplantation Rate After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML | 37.5 Percentage of participants |
Secondary
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
Population: All participants with FLT3-ITD positive relapsed or refractory AML and documented best response of CRc.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Initial Dose 30 mg/Day Quizartinib | Leukemia-free Survival (LFS) After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML | 16.1 weeks |
| Initial Dose 20 mg/Day Quizartinib | Leukemia-free Survival (LFS) After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML | NA weeks |
| Total | Leukemia-free Survival (LFS) After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML | 16.1 weeks |
Secondary
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
Population: All participants with FLT3-ITD positive relapsed or refractory AML.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Initial Dose 30 mg/Day Quizartinib | Overall Survival (OS) After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML | 34.1 weeks |
| Initial Dose 20 mg/Day Quizartinib | Overall Survival (OS) After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML | NA weeks |
| Total | Overall Survival (OS) After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML | 34.1 weeks |
Secondary
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
Population: All participants with FLT3-ITD positive relapsed or refractory AML who achieved CR, CRp, CRi, or PR, discontinued the study treatment, or completed response assessment at Cycle 4 Day 1.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Initial Dose 30 mg/Day Quizartinib | Response Rate After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML | 79.2 percentage of participants |
| Initial Dose 20 mg/Day Quizartinib | Response Rate After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML | 66.7 percentage of participants |
| Total | Response Rate After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML | 77.8 percentage of participants |