Neoplasms

Blood and Lymph Conditions

All Conditions

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Neoplasms by Histologic Type

Hematologic Diseases

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Anti-Infective Agents

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Cytarabine

Daunorubicin

Idarubicin

Quizartinib

Antimetabolites

Antiviral Agents

Immunosuppressive Agents

Immunologic Factors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Tyrosine

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.

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.

\[Induction period, Cycle 1\] 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.

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.

Global Clinical Leader

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

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)

De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/

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.

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.

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.

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.

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.

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.

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.

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.

Daiichi Sankyo Co., Ltd.

A treatment-emergent AE was defined as an 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 co-administered drugs, or the start date of new acute myeloid leukemia post-treatment, whichever was earlier. The serious AEs (SAEs) reported occurred only in the Induction phase. No SAEs occurred during the consolidation phase. TEAEs at ≥5% are reported for both induction and consolidation phases.

Quizartinib 20 mg/Day

Participants who received 40 mg/day 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.

Quizartinib 40 mg/Day

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

Japan

Region of Enrollment

Contact for Clinical Trial Information

Complete remission (CR)

CR with incomplete platelet recovery (CRp)

CR with incomplete hematological recovery (CRi)

Partial remission (PR)

No response (NR)

Best response was assessed in the Efficacy Analysis Set.

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)

Composite CR rate (CRc rate: CR+CRp+CRi)

Response rate (CRc+PR)

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

Cycle 1, Day 8: Quizartinib, Cmax

Cycle 1, Day 8: AC886, Cmax

Cycle 1, Day 8: Quizartinib + AC886, Cmax

Cycle 1, Day 21: Quizartinib, Cmax, ss

Cycle 1, Day 21: AC886, Cmax, ss

Cycle 1, Day 21: Quizartinib + AC886, Cmax

Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set.

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

Cycle 1, Day 8: Quizartinib, AUCtau

Cycle 1, Day 8: AC886, AUCtau

Cycle 1, Day 8: Quizartinib + AC886, AUCtau

Cycle 1, Day 21: Quizartinib, AUCtau,ss

Cycle 1, Day 21: AC886, AUCtau, ss

Cycle 1, Day 21: Quizartinib + AC886, AUCtau

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

Cycle 1, Day 8: Quizartinib, Tmax

Cycle 1, Day 8: AC886, Tmax

Cycle 1, Day 8: Quizartinib + AC886, Tmax

Cycle 1, Day 21: Quizartinib, Tmax,ss

Cycle 1, Day 21: AC886, Tmax,ss

Cycle 1, Day 21: Quizartinib + AC886, Tmax

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)

Cycle 1, Day 8: MR (Cmax)

Cycle 1, Day 8: MR (AUCtau)

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)

Cycle 1, Day 21: Quizartinib

Cycle 1, Day 21: AC886

Cycle 1, Day 21: Quizartinib + AC886

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)

Cycle 1, Day 21: Quizartinib AR (Cmax)

Cycle 1, Day 21: AC886 AR (Cmax)

Cycle 1, Day 21: Quizartinib + AC886 AR (Cmax)

Cycle 1, Day 21: Quizartinib AR (AUCtau)

Cycle 1, Day 21: AC886 AR (AUCtau)

Cycle 1, Day 21: Quizartinib + AC886 AR (AUCtau)

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)

Participants with TEAEs

Infections and Infestations

Pneumonia

Skin infection

Staphylococcal bacteraemia

Blood and Lymphatic System Disorders

Febrile neutropenia

Anaemia

Leukopenia

Neutropenia

Thrombocytopenia

Immune Disorders

Hypersensitivity

Metabolism and Nutrition Disorders

Decreased appetite

Hypoalbuminaemia

Hypokalaemia

Hypomagnesaemia

Hyponatraemia

Hypophosphataemia

Hypouricaemia

Tumour lysis syndrome

Nervous System Disorders

Dysgeusia

Dizziness

Eye Disorders

Photophobia

Cardiac Disorders

Palpitations

Vascular Disorders

Hypotension

Respiratory, Thoracic, and Mediastinal Disorders

Epistaxis

Oropharyngeal pain

Respiratory disorder

Gastrointestinal Disorders

Abdominal pain upper

Nausea

Constipation

Diarrhoea

Stomatitis

Cheilitis

Vomiting

Melaena

Hepatobiliary Disorders

Hepatic function abnormal

Skin and Subcutaneous Tissue Disorders

Alopecia

Rash

Rash maculo-papular

Dermatitis bullous

Dry skin

Musculoskeletal and Connective Tissue Disorders

Arthralgia

Musculoskeletal pain

Myalgia

Pain in extremity

Renal and Urinary Disorders

Haematuria

Proteinuria

Urinary tract pain

Reproductive System and Breast Disorders

Menorrhagia

General Disorders & Administration Site Conditions

Oedema peripheral

Pyrexia

Investigations

Gamma-glutamyltransferase increased

Alanine aminotransferase increased

Blood alkaline phosphatase increased

Electrocardiogram QT prolonged

Platelet count decreased

Weight decreased

White blood cell count decreased

Aspartate aminotransferase

Aspartate aminotransferase increased

Blood bilirubin increased

Blood lactate dehydrogenase increased

Blood pressure decreased

Lipase increased

Adverse events were assessed in the Safety Analysis Set.

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)

Lung infection

Upper respiratory tract infection

Injury, Poisoning, and Procedural Complications

Contusion

Fall

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)

Induction Phase

Consolidation Phase

Spots Global Cancer Trial Database for Study of Quizartinib in Japanese Patients With Newly Diagnosed Acute Myeloid Leukemia (AML)

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

Useful links and downloads for this trial