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Clinical Phase III Trial Treosulfan-based Conditioning Versus Reduced-intensity Conditioning (RIC)

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2016 by medac GmbH
Information provided by (Responsible Party):
medac GmbH Identifier:
First received: January 13, 2009
Last updated: April 21, 2016
Last verified: April 2016
This randomized allogeneic transplantation protocol compares i.v. Treosulfan-based conditioning therapy with reduced intensity i.v. Busulfan-based conditioning in adult AML and MDS patients at increased risk for standard conditioning therapies. The protocol is based on results of previous phase I/II trials evaluating Treosulfan/Fludarabine conditioning prior to allogeneic haematopoietic stem cell transplantation. The reference arm (reduced intensity i.v. Busulfan/Fludarabine) is considered to be accepted medical practice for the study patient population.

Condition Intervention Phase
Acute Myeloid Leukemia
Myelodysplastic Syndrome
Drug: Busulfan
Drug: Treosulfan
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Clinical Phase III Trial to Compare Treosulfan-based Conditioning Therapy With Busulfan-based Reduced-intensity Conditioning (RIC) Prior to Allogeneic Haematopoietic Stem Cell Transplantation in Patients With AML or MDS Considered Ineligible to Standard Conditioning Regimens

Resource links provided by NLM:

Further study details as provided by medac GmbH:

Primary Outcome Measures:
  • Event-free survival (EFS) [ Time Frame: within 2 years after transplantation ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Comparative evaluation of incidence of CTC grade III/IV mucositis/stomatitis between day -6 and day +28 [ Time Frame: between day -6 and day +28 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 960
Study Start Date: November 2008
Estimated Study Completion Date: March 2019
Estimated Primary Completion Date: January 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
Drug: Busulfan
4 x 0.8 mg/kg/d Intravenous Day -4 and -3
Experimental: 2
Drug: Treosulfan
10 g/m2/d Intravenous Day -4, -3, -2

Detailed Description:

To compare efficacy and safety of Treosulfan-based conditioning (test) with i.v. Busulfan-based reduced intensity conditioning (reference).

The statistical aim of the study is to show non-inferiority with respect to:

Event-free survival (EFS) within 2 years after transplantation. Events are defined as relapse of disease, graft failure or death (whatever occurs first).

  1. Comparative evaluation of incidence of CTC grade III/IV mucositis/stomatitis between day -6 and day +28
  2. Comparative evaluation of overall survival (OS) and cumulative incidence of relapse (RI) as well as non-relapse mortality (NRM) and transplantation-related mortality (TRM)within 2 years after transplantation
  3. Comparative evaluation of day +28 conditional cumulative incidence of engraftment
  4. Comparative evaluation of day +28 and day +100 incidence of complete donor-type chimerism
  5. Comparative evaluation of cumulative incidence of acute and chronic GvHD within 2 years after transplantation
  6. Comparative evaluation of incidence of other CTC grade III/IV adverse events between day -6 and day +28

Individual patients will be followed-up for at most 2 years after transplantation. Three confirmatory interim evaluations and one final analysis are planned, which allow to stop the trial as soon as the question of non-inferiority is answered (as outlined below). In addition, post-surveillance with respect to OS and EFS will be conducted one year after transplantation of the last randomised patient.


Ages Eligible for Study:   18 Years to 70 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Patients with acute myeloid leukaemia acc. to WHO, 2008 (AML in complete remission at transplant, i.e. blast counts < 5 % in bone marrow) or myelodysplastic syndrome acc. to WHO, 2008 (MDS with blast counts < 20 % in bone marrow during disease history) indicated for allogeneic haematopoietic progenitor cell transplantation but considered to be at increased risk for standard conditioning therapies according to the following criteria:

    • patients aged ≥ 50 years at transplant and / or
    • patients with a HCT-CI score > 2 [acc. to Sorror et al., 2005]
  2. Availability of an HLA-identical sibling donor (MRD) or HLA-identical unrelated donor (MUD). Donor selection is based on molecular high resolution typing (4 digits) of class II alleles of the DRB1 and DQB1 gene loci and molecular (at least) low resolution typing (2 digits) of class I alleles (i.e., antigens) of the HLA- A, B, and C gene loci. In case, no class I and class II completely identical donor (10 out of 10 gene loci) can be identified, one antigen disparity (class I) and/or one allele disparity (class II) between patient and donor are acceptable. Conversely, disparity of two antigens (irrespective of the involved gene loci) cannot be accepted. These definitions for the required degree of histocompatibility apply to the selection of related as well as of unrelated donors.
  3. Adult patients of both gender, age 18 - 70 years
  4. Karnofsky Index ≥ 60 %
  5. Written informed consent
  6. Men capable of reproduction and women of childbearing potential must be willing to consent to using a highly effective method of birth control such as condoms, implants, injectables, combined oral contraceptives, IUDs, sexual abstinence or vasectomised partner while on treatment and for at least 6 months thereafter

Exclusion Criteria:

  1. Patients with acute promyelocytic leukaemia with t(15;17)(q22;q12) and in CR1
  2. Patients considered contra-indicated for allogeneic HSCT due to severe concomitant illness (within three weeks prior to scheduled day -6):

    • patients with severe renal impairment like patients on dialysis or prior renal transplantation or S-creatinine > 3.0 x ULN or calculated creatinine-clearance < 60 ml/min
    • patients with severe pulmonary impairment, DLCOsb (Hb-adjusted)/or FEV1 < 50 % or severe dyspnoea at rest or requiring oxygen supply
    • patients with severe cardiac impairment diagnosed by echocardiography and LVEF < 40 %
    • patients with severe hepatic impairment indicated by hyperbilirubinaemia > 3 x ULN or ALT / AST > 5 x ULN
  3. Active malignant involvement of the CNS
  4. HIV-positivity, active non-controlled infectious disease under treatment (no decrease of CRP or PCT) including active viral liver infection
  5. Previous allogeneic HSCT
  6. Pleural effusion or ascites > 1.0 L
  7. Pregnancy or lactation
  8. Known hypersensitivity to treosulfan, busulfan and/or related ingredients
  9. Participation in another experimental drug trial within 4 weeks prior to day -6 of the protocol
  10. Non-cooperative behaviour or non-compliance
  11. Psychiatric diseases or conditions that might compromise the ability to give informed consent
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00822393

Contact: Anja Klein, PhD +49 4103 8006 ext 792
Contact: Jochen Kehne, PhD + 49 4103 8006 ext 388

Helsinki University Central Hospital, Dept. of Medicine Active, not recruiting
Helsinki, Finland, 00290
Centre Hospitalier Lyon Sud Recruiting
Lyon, France, 69495
Contact: Mauricette Michallet, MD    (+33) 47886 ext 2233   
Principal Investigator: Mauricette Michallet, MD, Prof         
Hopital Saint-Louis Recruiting
Paris, France, 75475
Contact: Gerard Socie, MD    (+33) 1-42-49-9639   
Principal Investigator: Gerard Socie, MD, Prof.         
Universitätsklinikum Carl Gustav Carus Dresden, Med. Klinik I Recruiting
Dresden, Germany, 01307
Contact: Friedrich Stölzel, MD    (+49) 351-458 ext 4673   
Principal Investigator: Friedrich Stölzel, MD         
Klinik für Knochenmarktransplantation Recruiting
Essen, Germany, 45122
Contact: Dietrich W. Beelen, MD, Prof.    (+49) 201-7 23 ext 3117   
Principal Investigator: Dietrich W Beelen, MD, Prof.         
Malteser Krankenhaus St. Franziskus-Hospital Recruiting
Flensburg, Germany, 24939
Contact: Helge Menzel, MD    (+49) 461-816 ext 2737   
Principal Investigator: Helge Menzel, MD         
Universitätsklinikum Freiburg Recruiting
Freiburg, Germany, 79106
Contact: Juergen Finke, MD, Prof.    +49(0)761-2 70-3 ext 3200   
Principal Investigator: Juergen Finke, MD, Prof.         
Universitätsmedizin Goettingen, Haematolgie und Onkologie Recruiting
Goettingen, Germany, 37075
Contact: Gerald Wulf, MD, Prof.    (+49) 551-39 ext 6303   
Principal Investigator: Gerald Wulf, MD, Prof.         
Asklepios Kliniken Hamburg GmbH Recruiting
Hamburg, Germany, 20099
Contact: Bertram Glass, MD, Prof.    +49(0)40-18 18-85 ext 3537   
Principal Investigator: Bertram Glass, MD, Prof.         
Universitätsklinikum Heidelberg Recruiting
Heidelberg, Germany, 69120
Contact: Peter Dreger, MD, Prof.    (+49) 6221-56 ext 8008   
Principal Investigator: Peter Dreger, MD, Prof.         
Friedrich-Schiller-Universität Jena Recruiting
Jena, Germany, 07747
Contact: Inken Hilgendorf, MD    (+49) 3641-932 ext 4664   
Principal Investigator: Inken Hilgendorf, MD         
Universitätsklinikum Koeln, Stammzelltransplantation Recruiting
Koeln, Germany, 50937
Contact: Christof Scheid, MD, Prof.    (+49) 221-478 86 ext 169   
Principal Investigator: Christof Scheid, MD, Prof.         
Universitätsklinikum Leipzig, Haematologie, internistische Onkologie Recruiting
Leipzig, Germany, 04109
Contact: Dietger Niederwieser, MD, Prof.    (+49) 341-97 ext 13050   
Principal Investigator: Dietger Niederwieser, MD, Prof.         
Johannes-Gutenberg-Universität Mainz, III. Medizinische Klinik Recruiting
Mainz, Germany, 55131
Contact: Eva Wagner, MD    (+49) 6131-17 ext 6924   
Principal Investigator: Eva Wagner, MD         
Klinikum Rechts der Isar der TU München, III. Med. Klinik Recruiting
Muenchen, Germany, 81675
Contact: Mareike Verbeek, MD    (+49) 89-4140 ext 5336   
Principal Investigator: Mareike Verbeek, MD         
Universitätsklinikum Münster Recruiting
Münster, Germany, 48129
Contact: Matthias Stelljes, MD, Prof.    (+49) 251-835 ext 2801   
Principal Investigator: Matthias Stelljes, MD, Prof.         
Klinikum Nürnberg, 5. Medizinische Klinik Recruiting
Nürnberg, Germany, 90419
Contact: Kerstin Schaefer-Eckhart, MD    (+49) 911- 3 98 ext 3656   
Principal Investigator: Kerstin Schaefer-Eckhart, MD         
Klinikum Oldenburg gGmbH Recruiting
Oldenburg, Germany, 26133
Contact: Jochen Casper, MD, Prof.    (+49) 441-403 ext 2904   
Principal Investigator: Jochen Casper, MD, Prof.         
Klinikum der Universität Regensburg Recruiting
Regensburg, Germany, 93053
Contact: Ernst Holler, MD, Prof.    (+49) 941-9 44 ext 5570   
Principal Investigator: Ernst Holler, MD, Prof.         
Universität Rostock Recruiting
Rostock, Germany, 18057
Contact: Christian Junghanss, MD, Prof.    (+49) 381-4 94 ext 7424   
Principal Investigator: Christian Junghanss, MD, Prof.         
Universität Tübingen Recruiting
Tübingen, Germany, 72076
Contact: Wolfgang Bethge, MD, Prof.    (+49) 7071-29- ext 8 31 76   
Principal Investigator: Wolfgang Bethge, MD, Prof.         
Stiftung Deutsche Klinik für Diagnostik Recruiting
Wiesbaden, Germany, 65191
Contact: Gernot Stuhler, MD, Prof.    (+49) 611-572 ext 169   
Principal Investigator: Gernot Stuhler, MD, Prof.         
Klinikum der Universität Würzburg Recruiting
Würzburg, Germany, 97070
Contact: Goetz U Grigoleit, MD    (+49) 931-2 01-4 ext 0942   
Principal Investigator: Goetz U Grigoleit, MD         
St. Istvan and St. Laszlo Hospital of Budapest Recruiting
Budapest, Hungary, 1097
Contact: Tamas Masszi, MD    (+36)1-4 5582 ext 18   
Principal Investigator: Tamas Masszi, MD, Prof.         
Azienda Ospedaliera Papa Giovanni XXIII Recruiting
Bergamo, Italy, 24127
Contact: Alessandro Rambaldi, MD    (+39) 030-2694 ext 92 0   
Principal Investigator: Alessandro Rambaldi, MD, Prof.         
Hematology University of Brescia Recruiting
Brescia, Italy, 1-25123
Contact: Domenico Russo, MD, Prof.    (+39) 0303996812 ext 811   
Principal Investigator: Domenico Russo, MD, Prof.         
Scientific Institute H. San Raffaele Recruiting
Milan, Italy, 20132
Contact: Fabio Ciceri, MD, Prof.    (+39) 02-26 43 ext 77 03   
Principal Investigator: Fabio Ciceri, MD, Prof.         
Ospedale Civile Pescara Active, not recruiting
Pescara, Italy, 65123
Policlinico Umberto I Univ. La Sapienza Recruiting
Rome, Italy, 00161
Contact: Anna P Iori, MD    (+39) 06-85795282   
Principal Investigator: Anna P Iori, MD         
Clinica Ematologica ed Unita di Terapie Cellulari 'Carlo Melzi' Recruiting
Udine, Italy, 33100
Contact: Francesca Patriarca, MD    (+39) 432 559 ext 662   
Principal Investigator: Francesca Patriarca, MD         
Policlinico GB Rossi (Borgo Roma), Div. di Ematologia Recruiting
Verona, Italy, 37134
Contact: Fabio Benedetti, MD    (+39) 045812 ext 4647   
Principal Investigator: Fabio Benedetti, MD         
Medical University of Gdansk Recruiting
Gdansk, Poland, 80-952
Contact: Andrzej Hellmann, MD, Prof.    (+48) 58-349 ext 22 30   
Principal Investigator: Andrzej Hellmann, MD, Prof.         
Silesian Medical University Recruiting
Katowice, Poland, 40-032
Contact: Sławomira Kyrcz-Krzemień, MD, Prof.    (+48) 32 256 ext 28 58   
Principal Investigator: Sławomira Kyrcz-Krzemień, MD, Prof.         
Sponsors and Collaborators
medac GmbH
Principal Investigator: Dietrich W. Beelen, MD University Hospital, Essen
  More Information

Additional Information:
Responsible Party: medac GmbH Identifier: NCT00822393     History of Changes
Other Study ID Numbers: MC-FludT.14/L  EudraCT-No.: 2008-002356-18 
Study First Received: January 13, 2009
Last Updated: April 21, 2016
Health Authority: Germany: Federal Institute for Drugs and Medical Devices
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Italy: The Italian Medicines Agency
France: Agence Nationale de Sécurité du Médicament et des produits de santé
Hungary: National Institute for Quality and Organizational Development in Healthcare and Medicines
Individual Participant Data  
Plan to Share IPD: Undecided

Keywords provided by medac GmbH:

Additional relevant MeSH terms:
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Leukemia, Myeloid
Neoplasms by Histologic Type
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Alkylating
Antineoplastic Agents
Myeloablative Agonists processed this record on December 08, 2016