Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    DaunoDouble | AML | Germany
Previous Study | Return to List | Next Study

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02140242
Recruitment Status : Recruiting
First Posted : May 16, 2014
Last Update Posted : August 6, 2020
Sponsor:
Collaborators:
Nationales Centrum für Tumorerkrankungen Dresden (NCT/UCC)
Masaryk University
Information provided by (Responsible Party):
Technische Universität Dresden

Tracking Information
First Submitted Date  ICMJE May 9, 2014
First Posted Date  ICMJE May 16, 2014
Last Update Posted Date August 6, 2020
Actual Study Start Date  ICMJE April 16, 2014
Estimated Primary Completion Date March 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 14, 2014)
  • response rate after first induction [ Time Frame: day 15 ]
    To investigate whether a higher dose of daunorubicin in induction chemotherapy leads to an increase in hematological good responders defined as having <5% myeloid blasts on day 15 after start of induction therapy.
  • Rate complete remissions [ Time Frame: day 35 after final induction ]
    To investigate whether the rate of complete remissions (CR) after single induction is similar to that after double induction in patients with good response to induction I.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 14, 2014)
  • rate cytogenetic and molecular complete remissions [ Time Frame: day 35 ]
    To investigate whether a higher dose of daunorubicin in induction chemotherapy will lead to an increase in cytogenetic and molecular complete remissions.
  • event-free survival (EFS) [ Time Frame: 5 years ]
    To investigate whether a higher dose of daunorubicin will lead to improved event-free survival (EFS), relapse-free survival (RFS) and overall survival (OS). To investigate whether EFS, RFS and OS are similar after single versus double induction in patients with good response to induction I.
  • relapse-free survival (RFS) [ Time Frame: 5 years ]
    To investigate whether a higher dose of daunorubicin will lead to improved event-free survival (EFS), relapse-free survival (RFS) and overall survival (OS). To investigate whether EFS, RFS and OS are similar after single versus double induction in patients with good response to induction I.
  • overall survival (OS) [ Time Frame: 5 years ]
    To investigate whether a higher dose of daunorubicin will lead to improved event-free survival (EFS), relapse-free survival (RFS) and overall survival (OS). To investigate whether EFS, RFS and OS are similar after single versus double induction in patients with good response to induction I.
  • Correlation between Minimal Residual Disease (MRD) and EFS, RFS, OS [ Time Frame: day 35 ]
    To correlate the level of cytogenetic and molecular minimal residual disease after induction treatment with survival outcomes EFS, RFS and OS.
  • Rate of induction deaths [ Time Frame: day 60 ]
    Rate of induction deaths (until day 60 or beginning of consolidation treatment - whichever occurs first)
  • Incidence of serious infectious complications [ Time Frame: day 35 ]
    Incidence of serious infectious complications Grades 3-4 (Common Toxicity Criteria for Adverse Effects (CTCAE) V4.0
  • Sonographic cardiac left ventricular ejection fraction [ Time Frame: day 35 ]
    Sonographic cardiac left ventricular ejection fraction
  • Serum levels of pro-brain natriuretic peptide (por-BNP) and Troponin-T [ Time Frame: day 35 ]
    Serum levels of pro-BNP and Trop-T
  • Incidence of CTCAE grade ≥3 cardiac complications [ Time Frame: day 35 ]
    Incidence of CTCAE grade ≥3 cardiac complications
  • Rate of early deaths [ Time Frame: week 2 ]
    Rate of early deaths (2 weeks)
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Comparison Between Two Dose Levels of Daunorubicin and Between One vs. Two Induction Cycles for Adult Patients With AML
Official Title  ICMJE Randomized Comparison Between Two Dose Levels of Daunorubicin and Between One Versus Two Cycles of Induction Therapy for Adult Patients With Acute Myeloid Leukemia ≤65 Years
Brief 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.
Detailed 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].

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Leukemia, Myelocytic, Acute
Intervention  ICMJE
  • Drug: study part 1 - dose daunorubicin
    standard induction dose of daunorubicin 60 mg/m2 on days 3-5
  • Procedure: induction cycles
    single induction cycle versus double induction cycles (only patients with good response after first induction) Allocation is randomized for cytogenetic risk.
Study Arms  ICMJE
  • Active Comparator: daunorubicin 60 mg/m2
    study part 1 - dose daunorubicin standard dose daunorubicin in induction 1 (60 mg/m2) on days 3-5
    Intervention: Drug: study part 1 - dose daunorubicin
  • Active Comparator: Double induction
    study part 2: induction cycles double induction (only patients with good response)
    Intervention: Procedure: induction cycles
  • Experimental: Single induction
    study part 2: induction cycles single induction (only patients with good response)
    Intervention: Procedure: induction cycles
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 14, 2014)
600
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE August 2021
Estimated Primary Completion Date March 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Annett Haake +049 - 0351 458 3965 annett.haake@ukdd.de
Contact: Frank Fiebig +049 - 0351 458 5198 frank.fiebig@ukdd.de
Listed Location Countries  ICMJE Germany,   Czechia
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02140242
Other Study ID Numbers  ICMJE TUD-2DAUNO-058
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Technische Universität Dresden
Study Sponsor  ICMJE Technische Universität Dresden
Collaborators  ICMJE
  • Nationales Centrum für Tumorerkrankungen Dresden (NCT/UCC)
  • Masaryk University
Investigators  ICMJE
Principal Investigator: Christoph Röllig, Prof. Dr. Medizinische Fakultät der TU Dresden, Medizinische Klinik und Poliklinik I
PRS Account Technische Universität Dresden
Verification Date August 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP