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

NCT02140242 | Completed Phase 3

• 1 other identifier: TUD-2DAUNO-058
• Study Type: interventional
• Target: 721
• Locations: 2 countries
• Sites: 38

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.

Conditions

Leukemia, Myelocytic, Acute

Keywords

AML; leukemia; induction treatment; daunorubicin; 7+3

Outcome Measures

Primary Outcomes (2)

• response rate after first induction

  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.

  day 15

• Rate complete remissions

  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.

  day 35 after final induction

Secondary Outcomes (11)

• rate cytogenetic and molecular complete remissions

  day 35

• event-free survival (EFS)

  5 years

• relapse-free survival (RFS)

  5 years

• overall survival (OS)

  5 years

• Correlation between Minimal Residual Disease (MRD) and EFS, RFS, OS

  day 35

Study Arms (3)

daunorubicin 60 mg/m2

ACTIVE COMPARATOR

study part 1 - dose daunorubicin standard dose daunorubicin in induction 1 (60 mg/m2) on days 3-5

Drug: study part 1 - dose daunorubicin

Double induction

ACTIVE COMPARATOR

study part 2: induction cycles double induction (only patients with good response)

Procedure: induction cycles

Single induction

EXPERIMENTAL

study part 2: induction cycles single induction (only patients with good response)

Procedure: induction cycles

Interventions

study part 1 - dose daunorubicin DRUG

standard induction dose of daunorubicin 60 mg/m2 on days 3-5

daunorubicin 60 mg/m2

induction cycles PROCEDURE

single induction cycle versus double induction cycles (only patients with good response after first induction) Allocation is randomized for cytogenetic risk.

Double induction; Single induction

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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
• 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

Sponsors & Collaborators

• Technische Universität Dresden: lead
• University Hospital Dresden: collaborator
• Masaryk University: collaborator

Study Sites (38)

Interní klinika LF Masarykovy univerzity a Fakultní nemocnice Brno

Brno, Czechia

Location

Faculty Hospital Hradec Králové, II. Clinic of international medicine

Hradec Králové, Czechia

Location

Fakultní nemocnice Olomouc

Olomouc, Czechia

Location

Fakultní nemocnice Královské Vinohrady

Prague, Czechia

Location

Ústav hematologie a krevní transfuze (ÚHKT)

Prague, Czechia

Location

Uniklinik RWTH Aachen

Aachen, 52074, Germany

Location

Klinikum Altenburger Land GmbH

Altenburg, Germany

Location

Klinikum Augsburg

Augsburg, Germany

Location

Sozialstiftung Bamberg Klinikum am Bruderwald

Bamberg, Germany

Location

Charite Campus Benjamin Franklin

Berlin, Germany

Location

Helios Klinikum Berlin-Buch

Berlin, Germany

Location

Klinikum Bielefeld

Bielefeld, Germany

Location

Augusta Kliniken Bochum Hattingen

Bochum, 44791, Germany

Location

Ev. Diakonie-Krankenhaus gGmbH Bremen

Bremen, Germany

Location

Klinikum Chemnitz GmbH

Chemnitz, Germany

Location

Carl.Thiem-Klinikum Cottbus gGmbH

Cottbus, Germany

Location

Universitätsklinikum Carl Gustav Carus Dresden

Dresden, Germany

Location

Krankenhaus Düren gem. GmbH

Düren, Germany

Location

Marienhospital Düsseldorf GmbH

Düsseldorf, Germany

Location

Universitätsklinikum Erlangen

Erlangen, Germany

Location

Universitätsklinikum Essen

Essen, Germany

Location

Johann Wolfgang Goethe-Universität Frankfurt am Main

Frankfurt am Main, Germany

Location

Universitätsklinikum Halle (Saale)

Halle, Germany

Location

Asklepios Klinik St. Georg

Hamburg, Germany

Location

St. Marien-Hospital Hamm

Hamm, Germany

Location

Universitätsklinikum Heidelberg

Heidelberg, Germany

Location

St. Bernward Krankenhaus Hildesheim

Hildesheim, Germany

Location

Universitätsklinikum Jena

Jena, 07740, Germany

Location

Westpfalz-Klinikum GmbH

Kaiserslautern, Germany

Location

Städtisches Krankenhaus Kiel

Kiel, Germany

Location

Gemeinschaftsklinikum Mittelrhein GmbH

Koblenz, Germany

Location

Universitätsklinikum Leipzig

Leipzig, Germany

Location

Universitätsklinikum Gießen und Marburg

Marburg, Germany

Location

Universitätsklinikum Münster

Münster, Germany

Location

Klinikum Nürnberg-Nord

Nuremberg, Germany

Location

Diakonie-Klinikum Schwäbisch Hall gGmbH

Schwäbisch Hall, Germany

Location

Robert-Bosch-Krankenhaus

Stuttgart, Germany

Location

Rems-Murr-Klinikum Winnenden

Winnenden, Germany

Location

Related Publications (1)

• Dendorfer SM, Schmidt-Brucken K, Kramer M, Steffen B, Schliemann C, Mikesch JH, Alakel N, Herbst R, Hanel M, Hanoun M, Kaufmann M, Weinbergerova B, Schafer-Eckart K, Sauer T, Neubauer A, Burchert A, Baldus CD, Mertova J, Jost E, Niemann D, Novak J, Krause SW, Scholl S, Hochhaus A, Held G, Szotkowski T, Rank A, Schmid C, Fransecky L, Kayser S, Schaich M, Fiebig F, Haake A, Schetelig J, Middeke JM, Stolzel F, Platzbecker U, Thiede C, Muller-Tidow C, Berdel WE, Ehninger G, Mayer J, Serve H, Bornhauser M, Rollig C. Randomized Comparison of Cardiotoxicity With 60 Versus 90 mg Daunorubicin in AML Induction Therapy. Am J Hematol. 2026 Jan 5. doi: 10.1002/ajh.70160. Online ahead of print.

  PMID: 41492073 DERIVED

Related Links

• study alliance
• University Hospital
• czech ECRIN center

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Leukemia

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Christoph Röllig, Prof. Dr.

  Medizinische Fakultät der TU Dresden, Medizinische Klinik und Poliklinik I

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 9, 2014
• First Posted: May 16, 2014
• Study Start: April 16, 2014
• Primary Completion: April 25, 2022
• Study Completion: April 25, 2022
• Last Updated: September 15, 2023

Record last verified: 2023-09

Locations

DE (33); CZ (5)