Treatment with Gemtuzumab Ozogamicin in addition to standard induction therapy and comparison of standard postremission therapy versus standard postremission therapy in combination with Glasdegib in patients with newly diagnosed acute myeloid leukemia.
- Conditions
- acute myeloid leukemia (AML)Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]
- Registration Number
- EUCTR2019-003913-32-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
- 252
•Patients with newly diagnosed CD33 positive acute myeloid leukemia according to the 2016 WHO classification
•Genetic and immunophenotypic assessment in the central laboratory
•No prior chemotherapy for leukemia except hydroxyurea to control hyperleukocytosis (=7 days) *
•Age =60 years, no upper age limit
•Eastern Cooperative Oncology Group performance status (ECOG PS) =2. See appendix 19.1
•Signed written informed consent
•Ability of patient to understand character and consequences of the clinical trial
•Non-pregnant and non-nursing women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test within a sensitivity of at least 25 mIU/mL within 72 hours prior to start of study treatment. A woman is considered of childbearing potential, i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile.
•WOCBP must be using an effective method of birth control to avoid pregnancy throughout the study and for 7 months after the last dose of the IMP. This includes effective contraception methods that can achieve a failure rate of less than 1% per year (e.g. hormonal contraceptive and condom, IUD/IUS and condom) or sterilization, resulting in a failure rate less than 1% per year.
•Fertile men must be willing and able to use an effective method of birth control (i.e. latex condoms) throughout the study for up to 7 months after the last dose of the IMP, if their sexual partners are WOCBP (acceptable methods see above). A man is considered fertile after puberty unless permanently sterile by bilateral orchidectomy.
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 102
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 150
• AML with PML-RARA or BCR-ABL1
• Patients with known active central nervous system (CNS) leukemia (assessed clinically).
• Prior treatment with a smoothened inhibitor (SMOi) and/or hypomethylating agent (HMA) for AML. (treatment of a preceding myelodysplastic syndrome (MDS) with HMA is not an exclusion criterion.)
• Inadequate renal function: creatinine >1.5 x upper normal serum level; estimated creatinine clearance =30 mL/min (calculated using the standard method for the institution).
• 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 sinusoidal obstruction syndrome (SOS), also known as hepatic veno-occlusive disease (VOD)
• Uncontrolled hypertension; severe obstructive or restrictive ventilation disorder
• Any one of the following ongoing or in the previous 6 months: myocardial infarction, 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, symptomatic congestive heart failure (CHF NYHA III/IV), cerebrovascular accident, transient ischemic attack or symptomatic pulmonary embolism; as well as bradycardia defined as <50 bpms
• QTc interval >470 msec using the Fridericia correction (QTcF).
• Uncontrolled infection
• 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.
• 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.
• Severe neurologic or psychiatric disorder interfering with ability of giving informed consent
• Known or suspected active alcohol or drug abuse
• Known positivity for human immunodeficiency virus (HIV), active hepatitis B virus (HBV), hepatitis C virus (HCV), or hepatitis A infection
• Evidence or history of severe non-leukemia associated bleeding diathesis or coagulopathy
• No consent for biobanking and for registration, storage and processing of the individual disease-characteristics and course as well as information of the family physician about study participation.
• Pregnancy and lactation
• 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
• Participation in a clinical study involving an investigational drug(s) (Phases 1-4) within 4 weeks prior to study entry.
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