Biology and Treatment Strategy of AML in Its Subgroups: Multicenter Randomized Trial by the German Acute Myeloid Leukemia Cooperative Group (AMLCG)

This study has been completed.
Sponsor:
Collaborators:
Deutsche Krebshilfe e.V., Bonn (Germany)
German Federal Ministry of Education and Research
Information provided by (Responsible Party):
Prof. Dr. Thomas Büchner, University Hospital Muenster
ClinicalTrials.gov Identifier:
NCT00266136
First received: December 14, 2005
Last updated: October 25, 2012
Last verified: October 2012
  Purpose

The study in patients with primary and secondary AML and high-risk MDS uses a risk-stratified, randomized design to evaluate the role of high-dose araC in induction, of G-CSF priming, and of autologous stem cell transplantation.


Condition Intervention Phase
Acute Myeloid Leukemia
Drug: Cytarabine
Drug: Thioguanine
Drug: Daunorubicin
Drug: Cyclophosphamide
Drug: G-CSF
Procedure: Autologous stem cell transplantation
Procedure: Allogeneic stem cell transplantation
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Factorial Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Risk-stratified Therapy for Primary and Secondary AML and MDS. A Randomized Study by AMLCG in Relation to Cytogenetically Defined Prognostic Factors (1) on the Role of High-dose AraC as Part of Double Induction, (2) on G-CSF Priming, and (3) on High-dose Chemotherapy With Stem Cell Transplantation

Resource links provided by NLM:


Further study details as provided by University Hospital Muenster:

Primary Outcome Measures:
  • Remission rate, Remission duration,Relapse-free survival, Overall survival, Event-free survival [ Time Frame: 12-18months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Time and dose compliance, Realisation of SCT, Toxicity according to WHO [ Time Frame: 12-18months ] [ Designated as safety issue: No ]

Enrollment: 3500
Study Start Date: June 1999
Study Completion Date: October 2012
Primary Completion Date: January 2007 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Cytarabine
    see protocol
    Drug: Thioguanine
    see protocol
    Drug: Daunorubicin
    see protocol
    Drug: Cyclophosphamide
    see protocol
    Drug: G-CSF
    see protocol
    Procedure: Autologous stem cell transplantation
    for details see protocol
    Procedure: Allogeneic stem cell transplantation
    for details see protocol
Detailed Description:

The present study by the German AML Cooperative Group has been designed in order to investigate the effects of AML typical therapeutic strategies for AML and related diseases. Thus, the entry criteria are age starting from 16 years with no upper age limit, de novo AML or AML secondary to chemotherapy or radiotherapy of another disease or myelodysplasia subtype RAEB with bone marrow blasts greater than 10 %. All randomization is stratified according to karyotype favorable / intermediate / unfavorable. Additional stratification is according to LDH </>= 700 U and age </>= 60 Y. Standard treatment is (A) double induction with TAD and HAM, consolidation with TAD and maintenance treatment with monthly AD-AT-AC-AT -, rotatingly. Experimental modifications to be compared with stan-dard treatment are (B) double induction with HAM-HAM, (C) multiple course G-CSF before and during chemotherapy courses and (D) instead of maintenance treatment myeloablative consolidation with Bu/Cy and autologous blood stem cell transplantation. Intent to treat conditions are guaranteed by randomization before induction treatment starts. In order to evaluate the effect of every single modification randomization to (C) is equally distributed to the patients in treatment arms (A) and (B) which is also true for the randomization to (D) (balanced randomization). Similarly balanced between treatment arms are the patients according to diagnosis, age and risk factors like serum LDH and karyotype. In order to adapt treatment intensity to age patients of 60 years and older receive the second induction course only in case of 5 % or more residual bone marrow blasts. In addition, the AraC dose in HAM is reduced to 1 instead of 3 g/sqm in this age group. Furthermore, there is no treatment arm including stem cell transplantation in patients of 60+ years. Pri-mary endpoint to compare the therapeutic strategies is event-free survival from treatment start (A, B, C) and from achievement of remission (D), respectively.

By this design the AMLCG 2000 trial can contribute relevant experiences on optimum therapeutic strategies for the biological subgroups of de novo AML, secondary AML and MDS. Furthermore, new biological subgroups and their significance related to treatment strategies can be defined.

  Eligibility

Ages Eligible for Study:   16 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Acute myeloid leukemia (de-novo AML, secondary AML, high-risk MDS)
  • Age 16 - no upper age limit
  • Written informed consent

Exclusion Criteria:

  • Severe comorbidity
  • Presence of other malignancy
  • Prior anti-leukemic treatment
  • Pregnancy
  • Severe psychiatric disorder or other circumstances which may compromise cooperation of the patients
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00266136

Locations
Germany
University of Muenster, Medical Center, Department of Medicine, Hematology and Oncology
Muenster, Germany, 48129
Sponsors and Collaborators
University Hospital Muenster
Deutsche Krebshilfe e.V., Bonn (Germany)
German Federal Ministry of Education and Research
Investigators
Study Chair: Thomas Buechner, MD PhD University of Muenster, Medical Center, Department of Medicine, Hematology and Oncology
  More Information

No publications provided by University Hospital Muenster

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Prof. Dr. Thomas Büchner, Prof. Dr. Thomas Büchner MD PhD, University Hospital Muenster, University Hospital Muenster
ClinicalTrials.gov Identifier: NCT00266136     History of Changes
Other Study ID Numbers: AMLCG 99, BMBF 01 GI 02070
Study First Received: December 14, 2005
Last Updated: October 25, 2012
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by University Hospital Muenster:
AML treatment, de-novo, secondary, high-risk MDS, chemotherapy, autologous SCT, adult

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Neoplasms by Histologic Type
Neoplasms
Cyclophosphamide
Cytarabine
Daunorubicin
Thioguanine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents
Antibiotics, Antineoplastic

ClinicalTrials.gov processed this record on April 17, 2014