Treatment with Quizartinib and High-dose Ara-C plus Mitoxantrone for patients with relapsed or refractory acute myeloid leukemia with FLT3-internal tandem duplicatio
- Conditions
- Relapsed/Refractory AML with FLT3-ITDTherapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]
- Registration Number
- EUCTR2018-002675-17-DE
- Lead Sponsor
- Ruprecht-Karls-University of Heidelberg Medical Faculty represented in law by Heidelberg University Hospital
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 80
1.Patients with acute myeloid leukemia according to the 2016 WHO classification (except acute promyelocytic leukemia) who are either
A)refractory to induction therapy or
B)relapsed after first line treatment including chemotherapy, autologous and/or allo-HCT (details below).
2.Positive for FLT3-ITD (defined as a ratio of mutant to wild-type alleles of at least 0.05; measured within 4 weeks before inclusion)#
3.ECOG performance status = 2. See appendix 18.1
4.Adequate renal function defined as creatinine clearance >50 mL/min (calculated using the standard method for the institution)
5.Discontinuation of prior AML treatment for at least
•10 days for cytotoxic agents and
•28 days for investigational drug treatment
before the start of study treatment (except hydroxyurea to control hyperleukocytosis)
6.Age = 18 years and = 75 years
7.Pregnancy and childbearing potential:
•Non-pregnant and non-nursing women
•Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test within a sensitivity of at least 25 mIU/mL within 48 hours prior to randomization (Women of childbearing potential” is defined as a sexually active mature woman who has not undergone a hysterectomy or who has had menses at any time in the preceding 24 consecutive months).
•WOCBP must agree to avoid getting pregnant while on therapy: WOCBP must either commit to continued abstinence from heterosexual intercourse or begin one acceptable method of birth control (IUD, tubal ligation, or partner’s vasectomy) during study and 6 months after end of study/treatment.
•Men must use a latex condom during any sexual contact with WOCBP, even if they have undergone a successful vasectomy and must agree to avoid to father a child during study and 6 months after end of study/treatment
8.Signed written informed consent
9.Ability of patient to understand character and consequences of the clinical trial
A)Refractory to induction therapy is defined as no CR, or CRi, or PR (according to standard criteria) [1] after 1 or 2 intensive induction cycles of at least 7 days of cytarabine 100-200mg/m² continuously or an equivalent regimen with cytarabine with total dose not less than 700mg/m² per cycle and 2 days of an anthracycline (e.g. daunorubicin, idarubicin).
B)Relapsed after first line therapy is defined as relapsed AML (according to standard criteria) [1] after a first line therapy including at least one intensive induction and consolidation therapy including (but not limited to) allo-HCT.
# Secondary exclusion if FLT3-ITD cannot be verified by central testing. Patient already receiving Quizartinib may continue taking it and will be excluded after the first treatment cycle.
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 70
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10
1.Acute promyelocytic leukemia (AML FAB M3 with t(15;17)(q22;q12) / PML-RARA)
2.Patients with known CNS leukemia
3.Isolated extramedullary manifestation of AML
4.Patients with a currently active” second malignancy other than non-melanoma skin cancer. Patients are not considered to have a currently active” malignancy if they have completed therapy for more than one year and are considered by their physician to be at less than 30% risk of relapse within one year
5.Hyperleukocytosis (leukocytes > 30,000/µl) at the time of study entry. 1)
6.Uncontrolled or significant cardiovascular disease, including any of the following:
oHistory of heart failure NYHA class 3 or 4
oLeft ventricular ejection fraction (LVEF) = 40% by echocardiogram (ECHO)
oHistory of uncontrolled angina pectoris or myocardial infarction within 12 months prior to screening
oHistory of second (Mobitz II) or third degree heart block or any cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted)
7.Inadequate liver function: ALT and AST = 2.5 x ULN), total bilirubin = 1.5 x ULN; Alkaline phosphatase = 2.5 x ULN. Known liver cirrhosis or history of veno-occlusive disease (VOD) or history of Sinusoidal Obstruction Syndrome (SOS)
8.Known positivity for HIV, active HBV, HCV or hepatitis A infection (active hepatitis B defined by HBs Ag positivity, active hepatitis C defined by positive virus load)
9.Uncontrolled active infection
10.Evidence or history of severe non-leukemia associated bleeding diathesis or coagulopathy
11.within 100 days after allo-HCT
12.clinically relevant Graft-versus-Host-Disease (GvHD) requiring initiation of treatment or treatment escalation within 21 days prior to screening
13.Any one of the following ongoing or in the previous 6 months: congenital long QT syndrome, Torsades de pointes, arrhythmias (including sustained ventricular tachyarrhythmia), right or left bundle branch block and bifascicular block, unstable angina, coronary/peripheral artery bypass graft, cerebrovascular accident, transient ischemic attack or symptomatic pulmonary embolism; as well as bradycardia defined as <50 bpms
14.QTc interval >450 msec using the Fredericia correction (QTcF).
15.Patients known to be refractory to platelet or packed red cell transfusions as per institutional guidelines, or who are known to refuse or who are likely to refuse blood product support.
16.Severe neurologic or psychiatric disorder interfering with ability of giving informed consent
17.Known or suspected active alcohol or drug abuse
18.No consent for registration, storage and processing of the individual disease-characteristics and course as well as information of the family physician about study participation.
19.Pregnancy and lactation
20.History of hypersensitivity to the investigational medicinal product or to any drug with similar chemical structure or to any excipient present in the pharmaceutical form of the investigational medicinal product
21.Prior treatment with quizartinib
1)These patients should be treated with hydroxyurea according to routine practice and are only allowed to enter into the study when leukocyte counts of 30,000/µl or below are reached. If hydroxyurea is not sufficient to control hyperleukocytosis, i.v. application of 100mg cytarabine continuously over 24 hours may be discussed with the Principle Investigator or the Medical Coordinator.
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