Acute Myeloid Leukemia, Leukemia
Conditions
Keywords
Newly diagnosed Acute Myeloid Leukemia, FLT3-ITD positive, Chemotherapy, Induction chemotherapy, Consolidation chemotherapy, Quizartinib, Feline McDonough sarcoma (FMS)-like tyrosine kinase 3, AC220, FLT3-ITD, AML
Brief summary
Quizartinib is an experimental drug. It is not approved for regular use. It can only be used in medical research. Adults might be able to join this study after bone marrow tests show they have a certain kind of blood cancer (FLT3-ITD AML). Participants will have an equal chance of receiving quizartinib or placebo along with their chemotherapy.
Detailed description
This is a phase 3, randomized, double-blind, placebo-control global study. The purpose of this study is to compare the effect of quizartinib versus placebo (administered with standard induction and consolidation chemotherapy, then administered as continuation therapy for up to 36 cycles) on overall survival in subjects with FLT3-internal tandem duplication (ITD) positive AML.
Interventions
DRUGChemotherapy
DRUGQuizartinib
DRUGPlacebo
Sponsors
Daiichi Sankyo
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Must be competent and able to comprehend, sign, and date an Ethics Committee (EC) or Institutional Review Board approved Informed Consent Form (ICF) before performance of any study-specific procedures or tests; 2. Is ≥18 years or the minimum legal adult age (whichever is greater) and ≤75 years (at Screening); 3. Newly diagnosed, morphologically documented primary AML or AML secondary to myelodysplastic syndrome or a myeloproliferative neoplasm, based on the World Health Organization (WHO) 2008 classification (at Screening); 4. Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (at the time the participant signs their first ICF); 5. Presence of FLT3-ITD activating mutation in bone marrow (allelic ratio of ≥3% FLT3-ITD/total FLT3); 6. Participant is receiving standard 7+3 induction chemotherapy regimen as specified in the protocol; 7. Adequate renal function defined as: a. Creatinine clearance \>50 mL/min, as calculated with the modified Cockcroft Gault equation 8. Adequate hepatic function defined as: 1. Total serum bilirubin (TBL) ≤1.5 × upper limit of normal (ULN) unless the participant has documented Gilbert's syndrome or the increase is related to increased unconjugated (indirect) bilirubin due to hemolysis; 2. Serum alkaline phosphatase, aspartate transaminase (AST) and alanine transaminase (ALT) ≤2.5 × ULN; 9. Serum electrolytes within normal limits: potassium, calcium (total, or corrected for serum albumin in case of hypoalbuminemia or ionized calcium) and magnesium. If outside of normal limits, participant will be eligible when electrolytes are corrected; 10. If a woman of childbearing potential, must have a negative serum pregnancy test upon entry into this study and must be willing to use highly effective birth control upon enrollment, during the treatment period and for 6 months following the last dose of investigational drug or cytarabine, whichever is later. A woman is considered of childbearing potential following menarche and until becoming postmenopausal (no menstrual period for a minimum of 12 months); 11. If male, must be surgically sterile or willing to use highly effective birth control upon enrollment, during the treatment period, and for 6 months following the last dose of investigational drug or cytarabine, whichever is later.
Exclusion criteria
1. Diagnosis of acute promyelocytic leukemia (APL), French-American-British classification M3 or WHO classification of APL with translocation, t(15;17)(q22;q12), or breakpoint cluster region-Abelson murine leukemia viral oncogene homolog 1 (BCR-ABL) positive leukemia (ie, chronic myelogenous leukemia in blast crisis); participants who undergo diagnostic workup for APL and treatment with all-trans retinoic acid (ATRA), but who are found not to have APL, are eligible (treatment with ATRA must be discontinued before starting induction chemotherapy). 2. Diagnosis of AML secondary to prior chemotherapy or radiotherapy for other neoplasms; 3. Prior treatment for AML, except for the following allowances: * Leukapheresis; * Treatment for hyperleukocytosis with hydroxyurea; * Cranial radiotherapy for central nervous system (CNS) leukostasis; * Prophylactic intrathecal chemotherapy; * Growth factor/cytokine support; 4. Prior treatment with quizartinib or other FLT3-ITD inhibitors; 5. Prior treatment with any investigational drug or device within 30 days prior to Randomization (within 2 weeks for investigational or approved immunotherapy) or currently participating in other investigational procedures; 6. History of known CNS leukemia, including cerebrospinal fluid positive for AML blasts; lumbar puncture is recommended for participants with symptoms of CNS leukemia to rule out extramedullary CNS involvement; 7. History of other malignancies, except adequately treated non-melanoma skin cancer, curatively treated in-situ disease, or other solid tumors curatively treated with no evidence of disease for at least 2 years; 8. Uncontrolled or significant cardiovascular disease, including any of the following: * Bradycardia of less than 50 beats per minute, unless the participant has a pacemaker; * Fridericia's Heart Rate Correction Formula (QTcF) interval \>450 msec; * Diagnosis of or suspicion of long QT syndrome (including family history of long QT syndrome); * Systolic blood pressure ≥180 mmHg or diastolic blood pressure ≥110 mmHg; * History of clinically relevant ventricular arrhythmias (eg, ventricular tachycardia, ventricular fibrillation, or Torsade de Pointes); * History of second (Mobitz II) or third degree heart block (participants with pacemakers are eligible if they have no history of fainting or clinically relevant arrhythmias while using the pacemaker); * History of uncontrolled angina pectoris or myocardial infarction within 6 months prior to Screening; * History of New York Heart Association Class 3 or 4 heart failure; * Known history of left ventricular ejection fraction (LVEF) ≤45% or less than the institutional lower limit of normal; * Complete left bundle branch block; 9. Active acute or chronic systemic fungal, bacterial, or viral infection not well controlled by antifungal, antibacterial or antiviral therapy; 10. Known active clinically relevant liver disease (eg, active hepatitis B, or active hepatitis C); 11. Known history of human immunodeficiency virus (HIV). Participants should be tested for HIV prior to Randomization if required by local regulations or EC; 12. History of hypersensitivity to any excipients in the quizartinib/placebo tablets; 13. Females who are pregnant or breastfeeding; 14. Otherwise considered inappropriate for the study by the Investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival in Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Date of randomization to the date of death due to any cause, up to approximately 3 years after enrollment | Overall survival is defined as the time from randomization until death from any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Complete Remission (CR) Rate at the End of Induction in Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Approximately Cycle 1 Day 21 (Induction) to end of Induction, up to approximately 120 days (each Induction cycle is up to 60 days) | Complete remission (CR) rate is defined as the percentage of participants achieving CR, defined as \<5% blasts, \>1000 neutrophils, \>100,000 platelets, and other \[defined as absence of extramedullary disease \[EMD\], blasts with rods, and leukemic blasts\], after induction |
| Composite CR Rate at the End of Induction in Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Approximately Cycle 1 Day 21 (Induction) to end of Induction, up to approximately 120 days (each Induction cycle is up to 60 days) | Composite complete remission (CRc) rate is defined as the percentage of participants whose best response is complete remission (CR), defined as \<5% blasts, \>1000 neutrophils, \>100,000 platelets, and other \[defined as absence of extramedullary disease \[EMD\], blasts with rods, and leukemic blasts\], or CR with incomplete neutrophil or platelet recovery (CRi) at the end of first Induction cycle. |
| Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Date of first dose up to 30 days after last dose, up to 36 cycles following continuation (approximately 6 years 11 months, each cycle is 28 days) | A treatment-emergent adverse event (TEAE) is defined as an adverse event that occur, having been absent before first dose of quizartinib or placebo, or have worsened in severity after initiating quizartinib or placebo. Adverse events collected more than 30 days after the last dose of quizartinib/placebo will not be considered TEAEs unless they are considered drug-related. |
| Number of Participants Achieving CR With FLT3-ITD Minimal Residual Disease Negativity at the End of Induction in Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Approximately Cycle 1 Day 21 (Induction phase) to end of Induction phase, up to approximately 120 days (each Induction cycle is up to 60 days) | Complete remission (CR) is defined as participants achieving CR defined as \<5% blasts, \>1000 neutrophils, \>100,000 platelets, and other \[defined as absence of extramedullary disease \[EMD\], blasts with rods, and leukemic blasts\]. Minimal or measurable residual disease is the presence of a small number of leukemic cells in the bone marrow of patients with AML below the level of detection using conventional morphologic assessment. |
| Event-free Survival in Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Date of randomization to the date of refractory disease, relapse, or death, up to approximately 3 years after enrollment | Event-free survival (EFS) is the time from randomization to the earliest date of either refractory disease (or treatment failure \[TF\]), relapse, or death from any cause. Refractory disease is defined as complete remission never achieved during Induction (CR: \>1000 neutrophils, \>100,000 platelets, \<5% blasts, and other \[defined as absence of extramedullary disease \[EMD\], blasts with rods, and leukemic blasts\]). For refractory disease, EFS event date is Day 1 (randomization). Relapse after CR is defined as ≥5% blasts, leukemic blasts, extramedullary leukemia, and presence of rods. This analysis is based on a response assessment with TF defined as not achieving response of CR, using a 42- day window from the start of the last cycle in Induction for CR evaluation. |
| Pharmacokinetic Parameter Area Under the Concentration Versus Time Curve at Steady State | Induction Cycle 1: Day 8, predose, 2-4 hours (hr) postdose on Days 8, 15, 21; Consolidation Cycle 1: Day 6, predose, 2-4 hr postdose on Days 6, 13, 19; Continuation Cycle 1: 2-4 hr postdose, Days 1, 8, 15; Cycle 2 Days 1 and 15 (each cycle, 28 days) | AUCss was assessed by population Pharmacokinetic (PK) analysis during Cycle 1 of each phase. |
| Pharmacokinetic Parameter Steady State, Maximum Plasma Concentration (Css,Max) | Induction Cycle 1: Day 8, predose, 2-4 hours (hr) postdose on Days 8, 15, 21; Consolidation Cycle 1: Day 6, predose, 2-4 hr postdose on Days 6, 13, 19; Continuation Cycle 1: 2-4 hr postdose, Days 1, 8, 15; Cycle 2 Days 1 and 15 (each cycle, 28 days) | Css,max was assessed by population PK analysis during Cycle 1 of each phase. |
| Pharmacokinetic Parameter Time to Maximum Plasma Concentration Steady State (Tmax,ss) | Induction Cycle 1: Day 8, predose, 2-4 hours (hr) postdose on Days 8, 15, 21; Consolidation Cycle 1: Day 6, predose, 2-4 hr postdose on Days 6, 13, 19; Continuation Cycle 1: 2-4 hr postdose, Days 1, 8, 15; Cycle 2 Days 1 and 15 (each cycle, 28 days) | Tmax,ss was assessed by population PK analysis during Cycle 1 of each phase. |
| Number of Participants Achieving Composite CR With FLT3-ITD Minimal Residual Disease Negativity at the End of Induction in Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Approximately Cycle 1 Day 21 (Induction phase) to end of Induction phase, up to approximately 120 days (each Induction cycle is up to 60 days) | Composite complete remission (CRc) is defined as \<5% blasts, \>1000 neutrophils, \>100,000 platelets, and other \[defined as absence of extramedullary disease \[EMD\], blasts with rods, and leukemic blasts\], or CR with incomplete neutrophil or platelet recovery (CRi). Minimal or measurable residual disease is the presence of a small number of leukemic cells in the bone marrow of patients with AML below the level of detection using conventional morphologic assessment. |
Countries
Argentina, Australia, Belgium, Brazil, Bulgaria, Canada, China, Croatia, Czechia, France, Germany, Hong Kong, Hungary, Israel, Italy, Japan, Poland, Portugal, Romania, Russia, Serbia, Singapore, South Korea, Spain, Taiwan, Ukraine, United Kingdom, United States
Participant flow
Recruitment details
A total of 539 participants who met all inclusion criteria and no exclusion criteria were randomized to treatment at 193 study sites in the following countries: Spain, Italy, Republic of Korea, Japan, China, US, France, Brazil, Germany, Russian Federation, Taiwan, Hungary, Czech Republic, Romania, Israel, Canada, Serbia, Poland, Portugal, Australia, Belgium, Bulgaria, Croatia, Ukraine, Singapore, and the UK. A total of 6 participants were randomized, but did not received treatment.
Participants by arm
| Arm | Count |
|---|---|
| Quizartinib Participants who were randomized to receive the quizartinib treatment regimen. | 268 |
| Placebo Participants who were randomized to receive placebo treatment regimen. | 271 |
| Total | 539 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 58 | 23 |
| Overall Study | Death | 0 | 1 |
| Overall Study | Failure to meet continuation criteria | 5 | 12 |
| Overall Study | Investigator decision | 10 | 7 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Non-protocol-specified AML therapy | 12 | 6 |
| Overall Study | Other reasons not specified | 16 | 11 |
| Overall Study | Pregnancy | 0 | 1 |
| Overall Study | Refractory disease | 41 | 70 |
| Overall Study | Relapse | 44 | 65 |
| Overall Study | Subject decision to stop study drug | 25 | 23 |
Baseline characteristics
| Characteristic | Placebo | Total | Quizartinib |
|---|---|---|---|
| Age, Continuous | 54.3 years STANDARD_DEVIATION 12.81 | 54.0 years STANDARD_DEVIATION 12.93 | 53.6 years STANDARD_DEVIATION 13.07 |
| Age, Customized <60 years | 162 Participants | 323 Participants | 161 Participants |
| Age, Customized ≥60 years | 109 Participants | 216 Participants | 107 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 78 Participants | 158 Participants | 80 Participants |
| Race/Ethnicity, Customized Black or African American | 5 Participants | 7 Participants | 2 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 24 Participants | 51 Participants | 27 Participants |
| Race/Ethnicity, Customized Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 163 Participants | 322 Participants | 159 Participants |
| Region of Enrollment Australia | 5 participants | 8 participants | 3 participants |
| Region of Enrollment Belgium | 3 participants | 7 participants | 4 participants |
| Region of Enrollment Brazil | 8 participants | 15 participants | 7 participants |
| Region of Enrollment Bulgaria | 1 participants | 2 participants | 1 participants |
| Region of Enrollment Canada | 5 participants | 13 participants | 8 participants |
| Region of Enrollment China | 11 participants | 20 participants | 9 participants |
| Region of Enrollment Croatia | 10 participants | 15 participants | 5 participants |
| Region of Enrollment Czechia | 15 participants | 32 participants | 17 participants |
| Region of Enrollment France | 12 participants | 25 participants | 13 participants |
| Region of Enrollment Germany | 7 participants | 17 participants | 10 participants |
| Region of Enrollment Hungary | 5 participants | 9 participants | 4 participants |
| Region of Enrollment Israel | 9 participants | 14 participants | 5 participants |
| Region of Enrollment Italy | 29 participants | 60 participants | 31 participants |
| Region of Enrollment Japan | 13 participants | 29 participants | 16 participants |
| Region of Enrollment Poland | 8 participants | 11 participants | 3 participants |
| Region of Enrollment Portugal | 6 participants | 9 participants | 3 participants |
| Region of Enrollment Romania | 11 participants | 17 participants | 6 participants |
| Region of Enrollment Russia | 6 participants | 19 participants | 13 participants |
| Region of Enrollment Serbia | 6 participants | 18 participants | 12 participants |
| Region of Enrollment Singapore | 2 participants | 8 participants | 6 participants |
| Region of Enrollment South Korea | 34 participants | 70 participants | 36 participants |
| Region of Enrollment Spain | 34 participants | 67 participants | 33 participants |
| Region of Enrollment Taiwan | 17 participants | 29 participants | 12 participants |
| Region of Enrollment Ukraine | 1 participants | 3 participants | 2 participants |
| Region of Enrollment United Kingdom | 0 participants | 1 participants | 1 participants |
| Region of Enrollment United States | 13 participants | 21 participants | 8 participants |
| Sex: Female, Male Female | 150 Participants | 294 Participants | 144 Participants |
| Sex: Female, Male Male | 121 Participants | 245 Participants | 124 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 130 / 265 | 156 / 268 |
| other Total, other adverse events | 258 / 265 | 258 / 268 |
| serious Total, serious adverse events | 146 / 265 | 124 / 268 |
Outcome results
Primary
Overall Survival in Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia
Overall survival is defined as the time from randomization until death from any cause.
Time frame: Date of randomization to the date of death due to any cause, up to approximately 3 years after enrollment
Population: Overall survival was assessed in the Intent-to-Treat Analysis Set.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Quizartinib | Overall Survival in Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | 31.9 months |
| Placebo | Overall Survival in Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | 15.1 months |
p-value: 0.032495% CI: [0.615, 0.979]Log Rank
Secondary
Complete Remission (CR) Rate at the End of Induction in Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia
Complete remission (CR) rate is defined as the percentage of participants achieving CR, defined as \<5% blasts, \>1000 neutrophils, \>100,000 platelets, and other \[defined as absence of extramedullary disease \[EMD\], blasts with rods, and leukemic blasts\], after induction
Time frame: Approximately Cycle 1 Day 21 (Induction) to end of Induction, up to approximately 120 days (each Induction cycle is up to 60 days)
Population: Complete remission was assessed in the Intent-to-Treat Analysis Set.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Quizartinib | Complete Remission (CR) Rate at the End of Induction in Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | 147 Participants |
| Placebo | Complete Remission (CR) Rate at the End of Induction in Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | 150 Participants |
Secondary
Composite CR Rate at the End of Induction in Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia
Composite complete remission (CRc) rate is defined as the percentage of participants whose best response is complete remission (CR), defined as \<5% blasts, \>1000 neutrophils, \>100,000 platelets, and other \[defined as absence of extramedullary disease \[EMD\], blasts with rods, and leukemic blasts\], or CR with incomplete neutrophil or platelet recovery (CRi) at the end of first Induction cycle.
Time frame: Approximately Cycle 1 Day 21 (Induction) to end of Induction, up to approximately 120 days (each Induction cycle is up to 60 days)
Population: Composite complete remission (CRc) rate was assessed in the Intent-to-Treat Analysis Set.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Quizartinib | Composite CR Rate at the End of Induction in Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | 192 Participants |
| Placebo | Composite CR Rate at the End of Induction in Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | 176 Participants |
Secondary
Event-free Survival in Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia
Event-free survival (EFS) is the time from randomization to the earliest date of either refractory disease (or treatment failure \[TF\]), relapse, or death from any cause. Refractory disease is defined as complete remission never achieved during Induction (CR: \>1000 neutrophils, \>100,000 platelets, \<5% blasts, and other \[defined as absence of extramedullary disease \[EMD\], blasts with rods, and leukemic blasts\]). For refractory disease, EFS event date is Day 1 (randomization). Relapse after CR is defined as ≥5% blasts, leukemic blasts, extramedullary leukemia, and presence of rods. This analysis is based on a response assessment with TF defined as not achieving response of CR, using a 42- day window from the start of the last cycle in Induction for CR evaluation.
Time frame: Date of randomization to the date of refractory disease, relapse, or death, up to approximately 3 years after enrollment
Population: Event-free survival was assessed in the Intent-to-Treat Analysis Set.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Quizartinib | Event-free Survival in Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | 0.03 months |
| Placebo | Event-free Survival in Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | 0.71 months |
Secondary
Number of Participants Achieving Composite CR With FLT3-ITD Minimal Residual Disease Negativity at the End of Induction in Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia
Composite complete remission (CRc) is defined as \<5% blasts, \>1000 neutrophils, \>100,000 platelets, and other \[defined as absence of extramedullary disease \[EMD\], blasts with rods, and leukemic blasts\], or CR with incomplete neutrophil or platelet recovery (CRi). Minimal or measurable residual disease is the presence of a small number of leukemic cells in the bone marrow of patients with AML below the level of detection using conventional morphologic assessment.
Time frame: Approximately Cycle 1 Day 21 (Induction phase) to end of Induction phase, up to approximately 120 days (each Induction cycle is up to 60 days)
Population: Composite complete remission (CRc) rate was assessed in the Intent-to-Treat Analysis Set.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Quizartinib | Number of Participants Achieving Composite CR With FLT3-ITD Minimal Residual Disease Negativity at the End of Induction in Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | 66 Participants |
| Placebo | Number of Participants Achieving Composite CR With FLT3-ITD Minimal Residual Disease Negativity at the End of Induction in Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | 58 Participants |
Secondary
Number of Participants Achieving CR With FLT3-ITD Minimal Residual Disease Negativity at the End of Induction in Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia
Complete remission (CR) is defined as participants achieving CR defined as \<5% blasts, \>1000 neutrophils, \>100,000 platelets, and other \[defined as absence of extramedullary disease \[EMD\], blasts with rods, and leukemic blasts\]. Minimal or measurable residual disease is the presence of a small number of leukemic cells in the bone marrow of patients with AML below the level of detection using conventional morphologic assessment.
Time frame: Approximately Cycle 1 Day 21 (Induction phase) to end of Induction phase, up to approximately 120 days (each Induction cycle is up to 60 days)
Population: Complete remission was assessed in the Intent-to-Treat Analysis Set.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Quizartinib | Number of Participants Achieving CR With FLT3-ITD Minimal Residual Disease Negativity at the End of Induction in Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | 54 Participants |
| Placebo | Number of Participants Achieving CR With FLT3-ITD Minimal Residual Disease Negativity at the End of Induction in Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | 51 Participants |
Secondary
Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia
A treatment-emergent adverse event (TEAE) is defined as an adverse event that occur, having been absent before first dose of quizartinib or placebo, or have worsened in severity after initiating quizartinib or placebo. Adverse events collected more than 30 days after the last dose of quizartinib/placebo will not be considered TEAEs unless they are considered drug-related.
Time frame: Date of first dose up to 30 days after last dose, up to 36 cycles following continuation (approximately 6 years 11 months, each cycle is 28 days)
Population: Treatment-emergent adverse events were assessed in the Safety Analysis Set.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Quizartinib | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Diarrhoea | 98 Participants |
| Quizartinib | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Hypomagnesaemia | 30 Participants |
| Quizartinib | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | General disorders and administration site disorders | 177 Participants |
| Quizartinib | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Hypophosphataemia | 27 Participants |
| Quizartinib | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Abdominal pain | 46 Participants |
| Quizartinib | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Hypocalcaemia | 26 Participants |
| Quizartinib | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Pyrexia | 112 Participants |
| Quizartinib | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Skin and subcutaneous tissue disorders | 152 Participants |
| Quizartinib | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Vomiting | 65 Participants |
| Quizartinib | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Rash | 69 Participants |
| Quizartinib | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Oedema peripheral | 30 Participants |
| Quizartinib | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Pruritus | 35 Participants |
| Quizartinib | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Dyspepsia | 30 Participants |
| Quizartinib | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Investigations | 140 Participants |
| Quizartinib | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Fatigue | 29 Participants |
| Quizartinib | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Alanine aminotransferase increased | 42 Participants |
| Quizartinib | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Gastrointestinal disorders | 215 Participants |
| Quizartinib | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Electrocardiogram QT prolonged | 36 Participants |
| Quizartinib | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Blood and lymphatic system disorders | 168 Participants |
| Quizartinib | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Aspartate aminotransferase increased | 28 Participants |
| Quizartinib | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Abdominal pain upper | 29 Participants |
| Quizartinib | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Neutrophil count decreased | 27 Participants |
| Quizartinib | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Febrile neutropenia | 117 Participants |
| Quizartinib | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Respiratory, thoracic, and mediastinal disorders | 123 Participants |
| Quizartinib | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Stomatitis | 57 Participants |
| Quizartinib | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Cough | 50 Participants |
| Quizartinib | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Neutropenia | 54 Participants |
| Quizartinib | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Epistaxis | 40 Participants |
| Quizartinib | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Infections and infestations | 204 Participants |
| Quizartinib | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Oropharyngeal pain | 27 Participants |
| Quizartinib | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Thrombocytopenia | 30 Participants |
| Quizartinib | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Nervous system disorders | 103 Participants |
| Quizartinib | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Nausea | 90 Participants |
| Quizartinib | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Headache | 73 Participants |
| Quizartinib | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Anaemia | 29 Participants |
| Quizartinib | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Musculoskeletal and connective tissue disorders | 91 Participants |
| Quizartinib | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Pneumonia | 39 Participants |
| Quizartinib | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Arthralgia | 29 Participants |
| Quizartinib | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Metabolism and nutrition disorders | 165 Participants |
| Quizartinib | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Back pain | 19 Participants |
| Quizartinib | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Constipation | 56 Participants |
| Quizartinib | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Vascular disorders | 71 Participants |
| Quizartinib | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Hypokalaemia | 93 Participants |
| Quizartinib | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Hypertension | 29 Participants |
| Quizartinib | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Sepsis | 15 Participants |
| Quizartinib | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Psychiatric disorders | 57 Participants |
| Quizartinib | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Decreased appetite | 46 Participants |
| Quizartinib | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Insomnia | 37 Participants |
| Quizartinib | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Any TEAE | 264 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Insomnia | 30 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Any TEAE | 265 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Gastrointestinal disorders | 209 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Diarrhoea | 94 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Nausea | 84 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Vomiting | 53 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Stomatitis | 56 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Constipation | 69 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Abdominal pain | 38 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Dyspepsia | 23 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Abdominal pain upper | 25 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Infections and infestations | 188 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Pneumonia | 41 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Sepsis | 28 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | General disorders and administration site disorders | 173 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Pyrexia | 109 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Oedema peripheral | 37 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Fatigue | 23 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Blood and lymphatic system disorders | 143 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Febrile neutropenia | 113 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Neutropenia | 27 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Thrombocytopenia | 30 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Anaemia | 19 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Metabolism and nutrition disorders | 153 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Hypokalaemia | 96 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Decreased appetite | 36 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Hypomagnesaemia | 30 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Hypophosphataemia | 24 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Hypocalcaemia | 29 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Skin and subcutaneous tissue disorders | 158 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Rash | 66 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Pruritus | 40 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Investigations | 105 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Alanine aminotransferase increased | 27 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Electrocardiogram QT prolonged | 11 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Aspartate aminotransferase increased | 19 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Neutrophil count decreased | 12 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Respiratory, thoracic, and mediastinal disorders | 115 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Cough | 44 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Epistaxis | 29 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Oropharyngeal pain | 18 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Nervous system disorders | 97 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Headache | 53 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Musculoskeletal and connective tissue disorders | 108 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Arthralgia | 35 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Back pain | 28 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Vascular disorders | 70 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Hypertension | 33 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia | Psychiatric disorders | 50 Participants |
Secondary
Pharmacokinetic Parameter Area Under the Concentration Versus Time Curve at Steady State
AUCss was assessed by population Pharmacokinetic (PK) analysis during Cycle 1 of each phase.
Time frame: Induction Cycle 1: Day 8, predose, 2-4 hours (hr) postdose on Days 8, 15, 21; Consolidation Cycle 1: Day 6, predose, 2-4 hr postdose on Days 6, 13, 19; Continuation Cycle 1: 2-4 hr postdose, Days 1, 8, 15; Cycle 2 Days 1 and 15 (each cycle, 28 days)
Population: PK Parameters were assessed in the PK Analyses set, which includes all participants in the Intent-to-Treat Analysis Set who received at least 1 dose of quizartinib and had at least 1 PK sample assessed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Quizartinib | Pharmacokinetic Parameter Area Under the Concentration Versus Time Curve at Steady State | Induction Period | 2680 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 84.9 |
| Quizartinib | Pharmacokinetic Parameter Area Under the Concentration Versus Time Curve at Steady State | Consolidation Period | 3930 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 77.6 |
| Quizartinib | Pharmacokinetic Parameter Area Under the Concentration Versus Time Curve at Steady State | Continuation Period - Dose 1 | 5080 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 74.7 |
| Quizartinib | Pharmacokinetic Parameter Area Under the Concentration Versus Time Curve at Steady State | Continuation Period - Dose 2 | 10200 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 74.7 |
Secondary
Pharmacokinetic Parameter Steady State, Maximum Plasma Concentration (Css,Max)
Css,max was assessed by population PK analysis during Cycle 1 of each phase.
Time frame: Induction Cycle 1: Day 8, predose, 2-4 hours (hr) postdose on Days 8, 15, 21; Consolidation Cycle 1: Day 6, predose, 2-4 hr postdose on Days 6, 13, 19; Continuation Cycle 1: 2-4 hr postdose, Days 1, 8, 15; Cycle 2 Days 1 and 15 (each cycle, 28 days)
Population: PK Parameters were assessed in the PK Analyses set, which includes all participants in the Intent-to-Treat Analysis Set who received at least 1 dose of quizartinib and had at least 1 PK sample assessed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Quizartinib | Pharmacokinetic Parameter Steady State, Maximum Plasma Concentration (Css,Max) | Induction Period | 140 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 71.2 |
| Quizartinib | Pharmacokinetic Parameter Steady State, Maximum Plasma Concentration (Css,Max) | Consolidation Period | 204 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 63.5 |
| Quizartinib | Pharmacokinetic Parameter Steady State, Maximum Plasma Concentration (Css,Max) | Continuation Period - Dose 1 | 265 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 59.7 |
| Quizartinib | Pharmacokinetic Parameter Steady State, Maximum Plasma Concentration (Css,Max) | Continuation Period - Dose 2 | 529 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 59.7 |
Secondary
Pharmacokinetic Parameter Time to Maximum Plasma Concentration Steady State (Tmax,ss)
Tmax,ss was assessed by population PK analysis during Cycle 1 of each phase.
Time frame: Induction Cycle 1: Day 8, predose, 2-4 hours (hr) postdose on Days 8, 15, 21; Consolidation Cycle 1: Day 6, predose, 2-4 hr postdose on Days 6, 13, 19; Continuation Cycle 1: 2-4 hr postdose, Days 1, 8, 15; Cycle 2 Days 1 and 15 (each cycle, 28 days)
Population: PK Parameters were assessed in the PK Analyses set, which includes all participants in the Intent-to-Treat Analysis Set who received at least 1 dose of quizartinib and had at least 1 PK sample assessed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Quizartinib | Pharmacokinetic Parameter Time to Maximum Plasma Concentration Steady State (Tmax,ss) | Induction Period | 2.68 hours |
| Quizartinib | Pharmacokinetic Parameter Time to Maximum Plasma Concentration Steady State (Tmax,ss) | Consolidation Period | 2.70 hours |
| Quizartinib | Pharmacokinetic Parameter Time to Maximum Plasma Concentration Steady State (Tmax,ss) | Continuation Period - Dose 1 | 2.73 hours |
| Quizartinib | Pharmacokinetic Parameter Time to Maximum Plasma Concentration Steady State (Tmax,ss) | Continuation Period - Dose 2 | 2.73 hours |