Study of Quizartinib in Combination With Standard Therapies in Chinese Participants With Newly Diagnosed Acute Myeloid Leukemia (AML)

A Study to Evaluate the Safety and Pharmacokinetics of Quizartinib in Combination With Standard Induction Therapy and Consolidation Therapy in Chinese Patients With Newly Diagnosed Acute Myeloid Leukemia

20 mg or 40 mg of quizartinib will be given to Chinese patients who were just diagnosed with AML. The study drug will be given to them along with standard therapies. The purpose is to find out the highest dose they can stand.

Study Overview

• Status: Completed
• Conditions: Acute Myeloid Leukemia (AML)
• Intervention / Treatment: Drug: Quizartinib

Detailed Description

This is a Phase 1, multicenter, open-label study to evaluate the safety and pharmacokinetics (PK) of quizartinib in combination with standard induction therapy and consolidation therapy in Chinese patients with newly diagnosed AML.

The quizartinib doses will be Level 1: 20 mg and Level 2: 40 mg. No increase in the quizartinib dose will be made in the same subject.

Dose-limiting toxicity associated with quizartinib occurring at each level will be assessed, and the maximum tolerated dose (MTD) will be decided using a 3 + 3 design.

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Tianjin, China, 300020
    • Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

• Has provided written informed consent for participation in the study
• Is aged 18 to 70 years at the time of enrollment into the study
• Has 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)
• Has Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2 at enrollment
• Has all of the required laboratory test results performed within 14 days prior to enrollment in the study.
• Is capable of orally taking quizartinib
• Is capable of being admitted to the hospital during the dose limiting toxicity (DLT) evaluation period
• If a woman of childbearing potential, has a negative serum pregnancy test upon entry into this study and is 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) unless permanently sterile (having undergone a hysterectomy, bilateral salpingectomy or bilateral oophorectomy).
• If male, is 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:

• Has diagnosis of acute promyelocytic leukemia (APL), French-American-British classification M3 or WHO classification of APL with translocation, t(15;17)(q22;q12), or BCR-ABL positive leukemia (ie, chronic myelogenous leukemia in blast crisis). Subjects 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).
• Has a diagnosis of AML secondary to prior chemotherapy or radiotherapy for other neoplasms

• Had prior treatment for AML, except for the following allowances:

  1. Leukapheresis
  2. Treatment for hyperleukocytosis with hydroxyurea
  3. Cranial radiotherapy for central nervous system (CNS) leukostasis
  4. Prophylactic intrathecal chemotherapy
  5. Growth factor or cytokine support
• Has received prior treatment with any investigational product or device within 30 days prior to enrollment in the study or is currently participating in other investigational procedures

• Has a history of other malignancies excluding the following:

  1. Adequately treated non-melanoma skin cancer
  2. Curatively treated in situ disease, or other solid tumors curatively treated with no evidence of disease for at least two years

• Has a past or current history of the following cardiovascular diseases:

  1. Heart rate of < 50 beats/min performed with 12-lead ECG within 14 days prior to enrollment in the study (excluding patients using a heart pacemaker)
  2. QT interval corrected by Fridericia (QTcF) of ≥ 450 msec performed with 12-lead ECG within 14 days prior to enrollment in the study
  3. Congenital long QT syndrome diagnosed or suspected (including family history of long QT syndrome)
  4. Systolic blood pressure ≥ 180 mmHg or diastolic blood pressure ≥ 110 mmHg measured within 7 days prior to enrollment in the study
  5. History of clinically significant ventricular arrhythmias [such as ventricular tachycardia, ventricular fibrillation, or Torsade de Pointes (TdP)]
  6. History of second (Mobitz II) or third-degree heart block (patients with pacemakers are eligible if they have no history of fainting or clinically relevant arrhythmias while using the pacemaker)
  7. History of uncontrolled angina pectoris or myocardial infarction within 6 months prior to enrollment in the study
  8. History of heart failure according to New York Heart Association (NYHA) Functional Classification: Class 3 or 4 heart failure
  9. Left ventricular ejection fraction (LVEF) of ≤ 45% or lower than the institutional lower limit of normal value per multi-gated acquisition scan (MUGA) or echocardiogram done within 30 days prior to enrollment
  10. Complete left bundle branch block
• Has active acute or chronic systemic fungal, bacterial, or viral infection not well controlled by antifungal, antibacterial, or antiviral therapy
• Has active clinically relevant liver disease (such as active hepatitis B or active hepatitis C).
• Has a history of human immunodeficiency virus (HIV). Patients will be tested for HIV prior to enrollment in the study, if required by local regulations or the Ethics Committee.
• Has a history of hypersensitivity to any excipients in the quizartinib tablets
• Is a female who is pregnant or breastfeeding
• Is considered inappropriate for the study by the investigator

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SEQUENTIAL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Quizartinib 20 mg; Participants receive 20 mg quizartinib in combination with standard induction therapy and consolidation therapy once daily in the fasted state in the morning (at least 1 hour before or two hours after a meal)	Drug: Quizartinib; Quizartinib is provided as 20 mg tablets for oral administration; Other Names: AC220; Experimental product
EXPERIMENTAL: Quizartinib 40 mg; Participants receive 40 mg quizartinib in combination with standard induction therapy and consolidation therapy once daily in the fasted state in the morning (at least 1 hour before or two hours after a meal)	Drug: Quizartinib; Quizartinib is provided as 20 mg tablets for oral administration; Other Names: AC220; Experimental product

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Dose-Limiting Toxicities		At the end of induction phase at approximately 56 days
Number of Participants with Adverse Events During the Trial		within approximately 19 months
Maximum Concentration (Cmax)	Categories: quizartinib, active metabolite	within 56 days
Time to Cmax (Tmax)	Categories: quizartinib, active metabolite	within 56 days
Area under the Plasma Concentration-Time Curve (AUC)	Categories: quizartinib, active metabolite	within 56 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Response	Categories: Complete remission (CR), CR with incomplete platelet or hematological recovery (CRi), partial remission (PR), no response (NR)	within approximately 19 months
Response Rates	Categories: response rate (CRc + PR), composite CR (CRc: CR + CRi) rate	within approximately 19 months

Collaborators and Investigators

• Sponsor: Daiichi Sankyo Co., Ltd.

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 5, 2018
• Primary Completion (ACTUAL): March 3, 2022
• Study Completion (ACTUAL): March 3, 2022

Study Registration Dates

• First Submitted: October 18, 2018
• First Submitted That Met QC Criteria: October 26, 2018
• First Posted (ACTUAL): October 29, 2018

Study Record Updates

• Last Update Posted (ACTUAL): July 29, 2022
• Last Update Submitted That Met QC Criteria: July 27, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
• Other Study ID Numbers: AC220-A-A103

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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/
• IPD Sharing 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.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No