Originele protocol

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