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Completed

NCT Number: NCT02834390

Study of Quizartinib in Japanese Patients With Newly Diagnosed Acute Myeloid Leukemia (AML)

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.

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Key information

Conditions

Acute Myeloid Leukemia Hematologic Diseases Hemic and Lymphatic Diseases Leukemia Leukemia, Myeloid Leukemia, Myeloid, Acute Neoplasms Neoplasms by Histologic Type

Age range

20 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Tokyo, Japan

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • No prior treatment for AML (including quizartinib)
  • ECOG (Eastern Cooperative Oncology Group) Performance Status of 0 to 2

Exclusion criteria

  • Diagnosis of acute promyelocytic leukemia
  • Active acute or chronic systemic fungal, bacterial, or viral infection not well controlled by antifungal, antibacterial or antiviral therapy.

Treatment and study plan

Quizartinib

Drug

[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.

Cytarabine

Drug

[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.

Idarubicin

Drug

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.

Daunorubicin

Drug

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.

Primary outcomes

  1. 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)

    Time frame: Day 0 to Day 21 of last completed cycle (each cycle 28 days), up to approximately 1 year

    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.

  2. Summary of Best Response Rates After the First Oral Dose of Quizartinib in Participants With Relapsed or Refractory Acute Myeloid Leukemia

    Time frame: Day 0 to Day 21 of last completed cycle (each cycle 28 days), up to approximately 1 year

    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.

  3. 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

    Time frame: Induction phase Cycle 1, Day 8 to Cycle 1, Day 21 (each cycle 28 days)

    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.

  4. 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

    Time frame: Induction phase Cycle 1, Day 8 to Cycle 1, Day 21 (each cycle 28 days)

    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.

  5. 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)

    Time frame: Induction phase Cycle 1, Day 8 to Cycle 1, Day 21 (each cycle 28 days)

    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.

  6. 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)

    Time frame: Induction phase Cycle 1, Day 8 (each cycle 28 days)

    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.

  7. 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)

    Time frame: Induction phase Cycle 1, Day 21 (each cycle 28 days)

    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.

  8. 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)

    Time frame: Induction phase Cycle 1, Day 21 (each cycle 28 days)

    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.

  9. 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)

    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

    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.

  10. 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)

    Time frame: Consolidation phase Cycle 1, Day 1 up to 35 days after last dose (each cycle 28 days), up to approximately 1 year

    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.

Sponsors and collaborators

Lead sponsor

Daiichi Sankyo Co., Ltd.

Industry

Registry information

Official study title

Phase 1b, Open-label, Dose Escalation Study of Quizartinib in Combination With Induction and Consolidation Chemotherapy in Japanese Patients With Newly Diagnosed Acute Myeloid Leukemia (AML)

Important dates

Study start
2016
Primary completion
2017
Study completion
2017
First posted
Jul 15, 2016
Registry last updated
Mar 5, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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