Newly diagnosed acute myeloid leukaemia (AML) in patients = 18 years of age MedDRA version: 20.0 Level: HLT Classification code 10024291 Term: Leukaemias acute myeloid System Organ Class: 100000004851
Conditions
Interventions
Trade Name: Hydrea
Product Name: Hydroxycarbamide
Pharmaceutical Form: Capsule, hard
Trade Name: Cerubidin
Product Name: Daunorubicin
Sponsors
University Hospital Karolinska
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Patients with: - a diagnosis of AML and related myeloid precursor neoplasia according to WHO 2008 classification (excluding acute promyelocytic leukemia) including secondary AML (after an antecedent hematological disease (e.g. MDS) and therapy-related AML, or - acute leukaemia of ambiguous lineage according to WHO 2008 • Patients 18 years and older. • Adequate renal and hepatic functions unless clearly disease related as indicated by the following laboratory values: - Serum creatinine = 220 µmol/L, unless considered AML-related - Serum bilirubin = 2.5 x upper limit of normal (ULN, i.e. =65 µmol/L), unless considered AML-related or due to Gilbert’s syndrome - Alanine aminotransferase (ALAT) = 2.5 x ULN, i.e. = 1.9 µcat/L and = 2.9 for females and males, respectively, unless considered AML-related • Male patients must use an effective contraceptive method during the study and for a minimum of 6 months after study treatment. • Written informed consent. • Patient is capable of giving informed consent. 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 36 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 33
Exclusion criteria
Exclusion criteria: • Acute promyelocytic leukemia. • CNS leukaemia • Ongoing treatment with gemtuzumab-ozogamicin. • Major organ failure precluding administration of planned chemotherapy. • Glomerular filtration rate (GFR) < 30 ml/min • Cardiac dysfunction as defined by: - Myocardial infarction within the last 3 months of study entry, or - Reduced left ventricular function with an ejection fraction < 40% as measured by echocardiogram (will only be performed when clinically suspected) or - Unstable angina or - New York Heart Association (NYHA) grade IV congestive heart failure (see Appendix I) or - Unstable cardiac arrhythmias • Known intolerance to any of the chemotherapeutic drugs in the protocol. • Positive pregnancy test. Lactating female or female of childbearing potential not using adequate contraception. • Fanconi anaemia • Patients with a history of non-compliance to medical regimens or who are considered unreliable with respect to compliance.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Following treatment cycle 2; Main Objective: 1. To assess the safety and tolerability of HU at three different dose-levels added to standard AML therapy consisting of ara-C and daunorubicin (frequency and severity of toxicities; dose-finding) 1. To assess the effect of HU added to standard AML therapy consisting of ara-C and daunorubicin on the rate of negative minimal residual disease (MRD-negativity) after the second standard chemotherapy cycle ; Secondary Objective: 1. To assess the time to haematopoietic recovery after each chemotherapy treatment cycle 2. To assess the effect of HU added to standard AML therapy consisting of ara-C and daunorubicin on ara-CTP accumulation in peripheral blasts 3. To assess the effect of HU added to standard AML therapy on remission (CR/CRi/MLFS) 4. To assess the effect of HU added to standard AML therapy on event-free survival (EFS) 5. To assess the effect of HU added to standard AML therapy on relapse-free survival (RFS) two years after diagnosis 6. To assess the effect of HU added to standard AML therapy on overall survival (OS) two years after diagnosis 7. To assess the role of SAMHD1 protein expression for secondary objectives 2-6 ; Primary end point(s): • MRD-negativity after cycle 2 Definition of MRD: malignant blasts as a percentage of total bone-marrow cells and as a percentage of the whole white blood cell compartment. These percentages are calculated based on the frequency of cells with an aberrant phenotype. It is nowadays well established that minimal residual disease (MRD) can be a clinical surrogate marker for survival, in particular relapse-free survival. A recent study of the Belgian-Dutch study consortium HOVON that is actively collaborating with the Swe | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Safety and tolerability (frequency and severity of non-hematological toxicities). • Time to hematopoietic recovery (ANC 0.5 and 1.0 x 109/L; platelets 50 x 109/L) after each chemotherapy treatment cycle, defined as the time from the start of the cycle until recovery. • Efficacy profile (response rate (CR, CRi, MLFS), event free survival (EFS), relapse-free survival (RFS), and overall survival (OS)) ; Timepoint(s) of evaluation of this end point: MRD-negativity after cycle 2 response rate (CR, CRi, MLFS, PR) after cycle 2 event free survival (EFS) and overall survival (OS) after the end of the trial ara-CTP amounts after first and second ara-C infusion on day 1 of cycle 1 | — |
Countries
Sweden
Contacts
Public ContactHEAT-AML Sweden
Karolinska University Hospital
Outcome results
None listed