This is a phase 1b, dose escalation, study of quizartinib to evaluate the safety profile, the pharmacokinetics, and the recommended dose of quizartinib for subsequent clinical studies of the combination of quizartinib and induction and consolidation chemotherapy.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
7
\[Induction period, Cycle 1\] Once-daily repeated oral administration Day 8 to Day 21. \[Induction period, Cycle 2\] Once-daily repeated oral administration Day 6 to Day 19. \[Consolidation period\] Once-daily repeated oral administration Day 6 to Day 19.
\[Induction period, Cycle 1\] Once-daily intravenous injection of 100 mg/m\^2 cytarabine on Day 1 to 7. \[Induction period, Cycle 2\] Once-daily intravenous injection of 100 mg/m\^2 cytarabine on Day 1 to 5. \[Consolidation period\] Twice-daily intravenous injection of 3.0 g/m\^2 cytarabine at 12-hour intervals on Days 1, 3, and 5.
Either Idarubicin or Daunorubicin will be used \[Induction period, Cycle 1\] Once-daily intravenous injection of 12 mg/m\^2 idarubicin on Day 1 to 3. \[Induction period, Cycle 2\] Once-daily intravenous injection of 12 mg/m\^2 idarubicin on Day 1 and 2.
Unnamed facility
Tokyo, Japan
Summary of Best Responses After a Daily Dose of 20 mg or 40 mg in Combination With Standard Chemotherapy to Japanese Participants With Newly Diagnosed Acute Myeloid Leukemia (AML)
Best response was defined as the best measured complete remission (CR), CR with incomplete hematological recovery (CRi), CR with incomplete platelet recovery (CRp), Partial remission (PR), or No response (NR) in the overall response assessments at all time points after the first dose. CR is defined as absence of leukemia cells morphologically; bone marrow blasts \<5 %; neutrophil count ≥ 1000 /mm 3; platelet count ≥ 100 ,000 /mm 3, independence of RBC transfusions for 4 weeks; independence of platelet transfusions for 1 week; absence of extramedullary leukemia.
Time frame: Day 0 to Day 21 of last completed cycle (each cycle 28 days), up to approximately 1 year
Summary of Best Response Rates After the First Oral Dose of Quizartinib in Participants With Relapsed or Refractory Acute Myeloid Leukemia
Best response was defined as the best measured complete remission (CR), CR with incomplete hematological recovery (CRi), CR with incomplete platelet recovery (CRp), Partial remission (PR), or No response (NR) in the overall response assessments at all time points after the first dose.
Time frame: Day 0 to Day 21 of last completed cycle (each cycle 28 days), up to approximately 1 year
Pharmacokinetic Parameter Maximum Serum Concentration (Cmax) of Geometric Means of Quizartinib and Active Metabolite (AC886) After Daily Dose of 20 mg or 40 mg Combined With Chemotherapy to Japanese Participants With Newly Diagnosed Acute Myeloid Leukemia
The maximum serum plasma concentration (Cmax) is reported at Induction phase Cycle 1, Day 9 and the maximum serum plasma concentration at steady state (Cmax,ss) is reported at Induction phase Cycle 1, Day 21 for quizartinib, active metabolite AC886, and quizartinib and AC886.
Time frame: Induction phase Cycle 1, Day 8 to Cycle 1, Day 21 (each cycle 28 days)
Pharmacokinetic Parameter Area Under the Concentration-Time Curve During Dosing Interval of Quizartinib and Metabolite (AC886) After Daily Dose of 20 mg or 40 mg With Chemotherapy to Japanese Participants With Newly Diagnosed Acute Myeloid Leukemia
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Either Idarubicin or Daunorubicin will be used \[Induction period, Cycle 1\] Once-daily intravenous injection of 60mg/m\^2 daunorubicin on Day 1 to 3. \[Induction period, Cycle 2\] Once-daily intravenous injection of 60mg/m\^2 daunorubicin on Day 1 and 2.
The area under the plasma concentration-time curve during dosing interval (AUCtau) of geometric means is reported at Induction phase Cycle 1, Day 9 and the area under the plasma concentration-time curve during dosing interval at steady state (AUCtauss) of geometric means are reported at Induction phase Cycle 1, Day 21 for quizartinib, active metabolite AC886, and quizartinib and AC886.
Time frame: Induction phase Cycle 1, Day 8 to Cycle 1, Day 21 (each cycle 28 days)
Pharmacokinetic Parameter Time of Maximum Plasma Concentration (Tmax) of Quizartinib and the Active Metabolite (AC886) After a Daily Dose of 20 mg or 40 mg Combined With Chemotherapy to Japanese Patients With Newly Diagnosed Acute Myeloid Leukemia (AML)
The time of maximum plasma concentration (Tmax) of geometric means is reported at Induction phase Cycle 1, Day 9 and the time of maximum plasma concentration at steady state (Tmax,ss) of geometric means is reported at Induction phase Cycle 1, Day 21 for quizartinib, active metabolite AC886, and quizartinib and AC886.
Time frame: Induction phase Cycle 1, Day 8 to Cycle 1, Day 21 (each cycle 28 days)
Pharmacokinetic Parameter Metabolite to Parent Ratio (MR) of Active Metabolite (AC886) After a Daily Dose of 20 mg or 40 mg Combined With Chemotherapy to Japanese Patients With Newly Diagnosed Acute Myeloid Leukemia (AML)
The metabolite to parent ratio of geometric means for Cmax and AUCtau is reported at Induction phase Cycle 1, Day 9 for active metabolite AC886 is reported.
Time frame: Induction phase Cycle 1, Day 8 (each cycle 28 days)
Pharmacokinetic Parameter Trough Plasma Concentration (Ctrough) of Quizartinib and Active Metabolite (AC886) After a Daily Dose of 20 mg or 40 mg Combined With Chemotherapy to Japanese Patients With Newly Diagnosed Acute Myeloid Leukemia (AML)
The trough plasma concentration (Ctrough) of geometric means is reported at Induction phase Cycle 1, Day 21 for serum quizartinib, active metabolite AC886, and quizartinib and AC886.
Time frame: Induction phase Cycle 1, Day 21 (each cycle 28 days)
Pharmacokinetic Parameter Accumulation Ratio (AR) of Quizartinib and Active Metabolite (AC886) After a Daily Dose of 20 mg or 40 mg Combined With Chemotherapy to Japanese Patients With Newly Diagnosed Acute Myeloid Leukemia (AML)
The accumulation ratio of geometric means for Cmax and AUCtau is reported at Induction phase Cycle 1, Day 21 for serum quizartinib, active metabolite AC886, and quizartinib and AC886.
Time frame: Induction phase Cycle 1, Day 21 (each cycle 28 days)
Number of Participants Treatment-Emergent Adverse Events Reported During Induction Phase After a Daily Dose of 20 mg or 40 mg in Combination With Standard Chemotherapy to Japanese Patients With Newly Diagnosed Acute Myeloid Leukemia (AML)
A treatment-emergent adverse event (TEAE) was defined as an adverse event (AE) that emerges (or worsens) from the first dose of study drug and coadministered drugs to the follow-up visit, 35 days after the last dose of study drug and coadministered drugs, or the start date of new AML post-treatment, whichever was earlier.
Time frame: Induction phase Cycle 1, Day 1 up to 35 days after last dose in Cycle 2 (each cycle 28 days), up to approximately 1 year
Number of Participants Treatment-Emergent Adverse Events Reported During Consolidation Phase After a Daily Dose of 20 mg or 40 mg in Combination With Standard Chemotherapy to Japanese Patients With Newly Diagnosed Acute Myeloid Leukemia (AML)
A treatment-emergent adverse event (TEAE) was defined as an adverse event (AE) that emerges (or worsens) from the first dose of study drug and coadministered drugs to the follow-up visit, 35 days after the last dose of study drug and coadministered drugs, or the start date of new AML post-treatment, whichever was earlier.
Time frame: Consolidation phase Cycle 1, Day 1 up to 35 days after last dose (each cycle 28 days), up to approximately 1 year