A Clinical Trial Study of Quizartinib Administered in Combination with Induction and Consolidation Chemotherapy, and Administered as Continuation Therapy in Subjects 18 to 75 Years Old with Newly Diagnosed Acute Myeloid Leukemia
- Conditions
- FMS-like tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD) (+) acute myeloid leukemia (AML)MedDRA version: 21.0Level: LLTClassification code 10000886Term: Acute myeloid leukemiaSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2015-004856-24-BG
- Lead Sponsor
- Daiichi Sankyo, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 539
1. Must be competent and able to comprehend, sign, and date an Ethics Committee or Institutional Review Board approved Informed Consent Form (ICF) before performance of any study-specific procedures or tests;
2. =18 years or the minimum legal adult age (whichever is greater) and
=75 years (at Screening);
3. 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);
4. Eastern Cooperative Oncology Group performance status 0-2 (at
Screening);
5. Presence of FLT3-ITD activating mutation in bone marrow (allelic ratio of =3% FLT3-ITD/total FLT3);
6. Subject is receiving standard 7+3 induction chemotherapy regimen as specified in the protocol;
7. Adequate renal function defined as: a. Creatinine clearance rate >50 mL/min, as calculated with the modified Cockcroft Gault equation;
8. Adequate hepatic function defined as:
a. Total serum bilirubin =1.5 × ULN unless the subject has documented Gilbert`s syndrome or the increase is related to increased unconjugated (indirect) bilirubin due to hemolysis;
b. Serum alkaline phosphatase, aspartate transaminase and alanine transaminase =2.5 × ULN;
9. Serum electrolytes within the instruction`s normal limits: potassium, calcium (total calcium, calcium corrected for serum albumin in case of hypoalbuminemia, or ionized calcium) and
magnesium. If outside the instruction`s of normal range, subject will be eligible when
electrolytes are corrected;
10. If a woman of childbearing potential, must have a negative serum
pregnancy test upon entry into this study and must be 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 (undergone a hysterectomy, bilateral salpingectomy or bilateral oophorectomy);
11. If male, must be 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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 268
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 268
1. 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).
2. Diagnosis of AML secondary to prior chemotherapy or radiotherapy for other neoplasms;
3. Prior treatment for AML, except for the following
allowances:
a. Leukapheresis;
b. Treatment for hyperleukocytosis with hydroxyurea;
c. Cranial radiotherapy for central nervous system (CNS) leukostasis;
d. Prophylactic intrathecal chemotherapy;
e. Growth factor/cytokine support;
4. Prior treatment with quizartinib or other FLT3-ITD inhibitors;
5. Prior treatment with any investigational drug or device within 30 days prior to Randomization (within 2 weeks for investigational or approved immunotherapy) or currently participating in other investigational procedures;
6. History of known CNS leukemia, including cerebrospinal fluid positive for AML blasts; lumbar puncture is recommended for subjects with symptoms of CNS leukemia to rule out extramedullary CNS involvement;
7. History of other malignancies, except adequately treated nonmelanoma skin cancer, curatively treated in-situ disease, or other solid tumors curatively treated with no evidence of disease for at least 2 years;
8. Uncontrolled or significant cardiovascular disease, including any of the following:
a. Bradycardia of less than 50 beats per minute, unless the subject has a pacemaker;
b. QTcF interval >450 msec;
c. Diagnosis of or suspicion of long QT syndrome (including family
history of long QT syndrome);
d. Systolic blood pressure =180 mmHg or diastolic blood pressure =110 mmHg;
e. History of clinically relevant ventricular arrhythmias (eg, ventricular
tachycardia, ventricular fibrillation, or Torsade de Pointes);
f. History of second (Mobitz II) or third degree heart block (subjects
with pacemakers are eligible if they have no history of fainting or clinically relevant arrhythmias while using the pacemaker);
g. History of uncontrolled angina pectoris or myocardial infarction within 6 months prior to Screening;
h. History of New York Heart Association Class 3 or 4 heart failure;
i. Left ventricular ejection fraction (LVEF) =45% or less than the institutional lower limit of normal per multi-gared acquisition scan (MUGA) or echocardiogram done within 30 days prior to randomization;
j. Complete left bundle branch block;
9. Active acute or chronic systemic fungal, bacterial, or viral infection not well controlled by antifungal, antibacterial or antiviral therapy;
10. Known active clinically relevant liver disease (eg, active hepatitis B,
or active hepatitis C)
11. Known history of human immunodeficiency virus (HIV). Subjects
should be tested for HIV prior to Randomization if required by local
regulations or EC;
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method