Inclusion criteria
- Informed consent
- Women or men with a newly diagnosed APL by cytomorphology, confirmed by molecular analysis*
- Age ≥18 and ≤ 65 years
- ECOG performance status 0-3
- WBC at diagnosis > 10 GPt/l
- Serum total bilirubin ≤ 3.0 mg/dl (≤ 51 μmol/l)
- Serum creatinine ≤ 3.0 mg/dl (≤ 260 μmol/l)
- Women must fulfill at least one of the following criteria in order to be eligible for trial inclusion:
- Post-menopausal (12 months of natural amenorrhea or 6 months of amenorrhea with Serum FSH > 40 U/ml)
- Postoperative (i.e. 6 weeks) after bilateral ovariectomy with or without hysterectomy
- Continuous and correct application of a contraception method with a Pearl
- Index of <1% (e.g. implants, depots, oral contraceptives, intrauterine device IUD).
- Sexual abstinence
- Vasectomy of the sexual partner
Exclusion criteria
- Patients who are not eligible for chemotherapy as per discretion of the treating physician
- APL secondary to previous radio- or chemotherapy for non-APL disease
- Other active malignancy at time of study entry (exception: basal-cell carcinoma)
- Lack of diagnostic confirmation of APL at genetic level (*see above)
- Significant arrhythmias, ECG abnormalities:
- Congenital long QT syndrome;
- History or presence of significant ventricular or atrial tachyarrhythmia;
- Clinically significant resting bradycardia (<50 beats per minute)
- QTc >500msec on screening ECG for both genders (using the QTcF formula detailed on protocol)
- Right bundle branch block plus left anterior hemiblock, bifascicular block
- Other cardiac contraindications for intensive chemotherapy (L-VEF <50%)
- Uncontrolled, life-threatening infections
- Severe non controlled pulmonary or cardiac disease
- Severe hepatic or renal dysfunction
- HIV and/or active hepatitis infection
- active multiple sclerosis (patients with inactive MS can be included)
- Pregnant or breast-feeding patients
- Allergy to trial medication or excipients in study medication
- Substance abuse; medical, psychological or social conditions that may interfere with
- the patients participation in the study or evaluation of the study results
- Use of other investigational drugs at the time of enrolment or within 30 days before study entry
