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

NCT02834390 | Completed Phase 1 Results FDA Drug

• 1 other identifier: AC220-A-J102
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Acute Myeloid Leukemia

Keywords

AML; phase 1; hematology; malignancy; newly diagnosed

Outcome Measures

Primary Outcomes (10)

• 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.

  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.

  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.

  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

  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.

  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.

  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.

  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.

  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.

  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.

  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.

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

Study Arms (2)

Quizartinib 20 mg/day

EXPERIMENTAL

Participants who received 20 mg quizartinib once daily in the morning under fasting conditions. For the Induction phase, cytarabine (100 mg/m\^2/day IV) and either idarubicin (12 mg/m\^2/day IV infusion) or daunorubicin (60 mg/m\^2/day IV) were co-administered with quizartinib. For the Consolidation phase, cytarabine (3.0 g/m\^2/12 hours IV) was co-administered with quizartinib.

Drug: Quizartinib; Drug: Cytarabine; Drug: Idarubicin; Drug: Daunorubicin

Quizartinib 40 mg/day

EXPERIMENTAL

Participants who received 40 mg quizartinib once daily in the morning under fasting conditions. For the Induction phase, cytarabine (100 mg/m\^2/day IV) and either idarubicin (12 mg/m\^2/day IV infusion) or daunorubicin (60 mg/m\^2/day IV) were co-administered with quizartinib. For the Consolidation phase, cytarabine (3.0 g/m\^2/12 hours IV) was co-administered with quizartinib.

Drug: Quizartinib; Drug: Cytarabine; Drug: Idarubicin; Drug: Daunorubicin

Interventions

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.

Quizartinib 20 mg/day; Quizartinib 40 mg/day

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.

Quizartinib 20 mg/day; Quizartinib 40 mg/day

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.

Quizartinib 20 mg/day; Quizartinib 40 mg/day

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.

Quizartinib 20 mg/day; Quizartinib 40 mg/day

Eligibility Criteria

• Age: 20 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Daiichi Sankyo Co., Ltd.: lead

Study Sites (1)

Unknown Facility

Tokyo, Japan

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Neoplasms

Interventions

quizartinib; Cytarabine; Idarubicin; Daunorubicin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Results Point of Contact

• Title: Contact for Clinical Trial Information
• Organization: Daiichi Sankyo, Inc.

CTRinfo@dsi.com

908-992-6400

Study Officials

• Global Clinical Leader

  Daiichi Sankyo

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 13, 2016
• First Posted: July 15, 2016
• Study Start: August 12, 2016
• Primary Completion: October 19, 2017
• Study Completion: October 19, 2017
• Last Updated: March 5, 2025
• Results First Posted: August 19, 2021

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
• Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.

Locations

JP (1)