Acute Myeloid Leukemia (AML)
Conditions
Brief summary
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.
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.
Interventions
DRUGQuizartinib
Quizartinib is provided as 20 mg tablets for oral administration
Sponsors
Daiichi Sankyo Co., Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants with Adverse Events During the Trial | within approximately 19 months | — |
| Time to Cmax (Tmax) | within 56 days | Categories: quizartinib, active metabolite |
| Area under the Plasma Concentration-Time Curve (AUC) | within 56 days | Categories: quizartinib, active metabolite |
| Number of Participants with Dose-Limiting Toxicities | At the end of induction phase at approximately 56 days | — |
| Maximum Concentration (Cmax) | within 56 days | Categories: quizartinib, active metabolite |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Response Rates | within approximately 19 months | Categories: response rate (CRc + PR), composite CR (CRc: CR + CRi) rate |
| Number of Participants with Response | within approximately 19 months | Categories: Complete remission (CR), CR with incomplete platelet or hematological recovery (CRi), partial remission (PR), no response (NR) |
Countries
China
Outcome results
None listed