Comparison Between Two Dose Levels of Daunorubicin and Between One vs. Two Induction Cycles for Adult Patients With AML

• Status: Recruiting
• Trial end date: 2022-05-01
• Target enrollment: 0
• Participant gender: All

Summary

The proposed trial will address two clinically important questions for younger patients with newly diagnosed acute myeloid leukemia (AML): the optimal dose of daunorubicin in induction therapy and the necessity of a second induction cycle in patients with a good response after the first induction. The primary endpoint is the rate of good responders. Secondary outcomes will be relapse-free survival, overall survival and minimal residual disease kinetics. Patients will be recruited in about 40 treatment centers of the Study Alliance Leukemia study group over a period of 40 months. The results will be of great clinical relevance: First, the study could facilitate the establishment or confirmation of the optimal daunorubicin dose.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Technische Universität Dresden
• Collaborators: Masaryk University; Universitäts KrebsCentrum des Universitätsklinikums und der Medizinischen Fakultät an der TU Dresden; Universitätsklinikum Dresden, Nationales Centrum für Tumorerkrankungen Dresden (NCT/UCC)
• Treatments: Daunorubicin

Criteria

Inclusion Criteria:

• Newly diagnosed AML other than acute promyelocytic leukemia (APL) according to WHO criteria, i.e. bone marrow aspirate or biopsy must contain ≥20% blasts of all nucleated cells or differential blood count must contain ≥20% blasts. In acute erythroid leukemia, ≥20% blasts in all non-erythroid bone marrow cells. In AML defined by cytogenetic aberrations, the rate of blasts may be <20%. Secondary AMLs are eligible for inclusion.

• Age 18- inkl.65 years

• Eastern Cooperative Oncology Group (ECOG) performance status 0-2

• Adequate liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to screening:

• Total bilirubin ≤ 1.5 times the upper limit of normal

• alanine transaminase (ALT) and aspartate transaminase (AST) ≤ 2.5 times upper limit of normal

• Creatinine ≤ 1.5 times upper limit of normalExclusion Criteria:

• Adequate cardiac function, i.e. left ventricular ejection fraction (LVEF) of ≥ 50% as assessed by transthoracic two-dimensional echocardiography ("M Mode") or multiple gated acquisition scan (MUGA scan)

• Signed informed consent

• 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 follicle stimulating hormone (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 standard chemotherapy as assessed by the treating physician

• Central nervous system manifestation of AML

• Cardiac disease: i.e. heart failure New York Heart Association (NYHA) III or IV; unstable coronary artery disease (MI more than 6 months prior to study entry is permitted); serious cardiac ventricular arrhythmias requiring anti-arrhythmic therapy

• Patients undergoing renal dialysis

• Chronic pulmonary disease with clinical relevant hypoxia

• Known HIV or Hepatitis infection

• Uncontrolled active infection

• Medical conditions other than AML with an estimated life expectancy below 6 months

• Previous treatment of AML except hydroxyurea up to 5 days

• Relapsed or primary refractory AML

• Acute promyelocytic leukemia

• Previous anthracycline-containing chemotherapy

• Treatment with any known non-marketed drug substance or experimental therapy within 4 weeks prior to enrollment

• Incapability of understanding purpose and possible consequences of the trial

• Pregnant or breastfeeding women

• Evidence suggesting that the patient is not likely to follow the study protocol (e.g. lacking compliance)