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

  • STATUS
    Recruiting
  • End date
    Aug 12, 2021
  • participants needed
    600
  • sponsor
    Technische Universität Dresden
Updated on 12 August 2020
Investigator
Annett Haake
Primary Contact
Universit tsklinikum Erlangen (9.4 mi away) Contact
+40 other location
ejection fraction
minimal residual disease
daunorubicin
residual tumor
neoadjuvant therapy
acute promyelocytic leukemia

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.

Description

In the first part of the trial, patients will be randomly assigned to receive either 90 mg/m2 or 60 mg/m2 daunorubicin in the first induction cycle in addition to standard dosed cytarabine. Assuming a superiority of 90 mg/m2, 436 patients will be recruited. In the second part of the trial, good responders will be randomized to receive either a second or no further induction cycle. Assuming a non-inferiority of the single induction regarding the rate of complete remissions, a number of 360 patients will be included in the second part. Furthermore, in case of a non-inferiority of single versus double induction in good responders, about half of all younger AML patients could be spared a second induction cycle, leading to a reduction in treatment-related mortality, fewer days spent in hospital and improved quality of life.

As a result of the preplanned interim analysis of part I, the sponsor decided to suspend randomization in trial part I and to offer all patients the standard dose of 60 mg/m2 daunorubicin in both induction cycles (part I and II of the trial). Because of this an Amendment was sent to and approved by regulatories and ethics comitee.

The inclusion age was raised to 65 years based on the current German treatment guidelines in which patients up to the age of 65 are considered eligible for intensive induction chemotherapy with DA60 [Onkopedia-Leitlinie 2017].

Details
Treatment study part 1 - dose daunorubicin, induction cycles
Clinical Study IdentifierNCT02140242
SponsorTechnische Universität Dresden
Last Modified on12 August 2020

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Eligibility

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Inclusion Criteria

Is your age between 18 yrs and 65 yrs?
Gender: Male or Female
Do you have any of these conditions: Acute myeloid leukemia or Acute Myelogenous Leukemia (AML)?
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)
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