Dose-Reduced Versus Standard Conditioning Prior Allo SCT for MDS/sAML Patients


Tracking Information

Start Date  ICMJEMay 2004
Estimated Primary Completion DateMay 2012   (final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE 
 (submitted: September 17, 2008)
non relapse mortality [ Time Frame: every 6 months for safety and in the final analysis at one year after allogeneic stem cell transplantation ] [ Designated as safety issue: Yes ]
Original Primary Outcome Measures  ICMJE 
 (submitted: May 16, 2008)
The hypothesis is that a dose-reduced conditioning will reduce the non-relapse mortality from 40% to 20% at one year after allogeneic stem cell transplantation. [ Time Frame: 1 year after SCT ] [ Designated as safety issue: No ]
Change HistoryComplete list of historical versions of study NCT00682396 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE 
 (submitted: September 17, 2008)
  • organ related toxicity of conditioning [ Time Frame: every 6 months for safety and in the final analysis at day +30 after allogeneic stem cell transplantation ] [ Designated as safety issue: Yes ]
  • Incidence of aGvHD [ Time Frame: every 6 months for safety and in the final at day +100 after allogeneic stem cell transplantation ] [ Designated as safety issue: Yes ]
  • Incidence of cGvHD [ Time Frame: every 6 months for safety and in the final analysis at one year after allogeneic stem cell transplantation ] [ Designated as safety issue: Yes ]
  • overall survival [ Time Frame: every 6 months for safety and in the final analysis at 2 years after allogeneic stem cell transplantation ] [ Designated as safety issue: Yes ]
  • event-free survival [ Time Frame: every 6 months for safety and in the final analysis at 2 years after allogeneic stem cell transplantation ] [ Designated as safety issue: Yes ]
  • cumulative incidence of relapse [ Time Frame: every 6 months for safety and in the final analysis at 2 years after allogeneic stem cell transplantation ] [ Designated as safety issue: Yes ]
  • VOD [ Time Frame: every 6 months for safety and in the final analysis at day +100 after allogeneic stem cell transplantation ] [ Designated as safety issue: Yes ]
  • infection incidence [ Time Frame: every 6 months for safety and in the final analysis at day +100, 1 year and 2 years after allogeneic stem cell transplantation ] [ Designated as safety issue: Yes ]
  • Haematopoietic recovery [ Time Frame: every 6 months for safety and in the final analysis at day +30 after allogeneic stem cell transplantation ] [ Designated as safety issue: Yes ]
Original Secondary Outcome Measures  ICMJE 
 (submitted: May 16, 2008)
Comparison of: hematopoeitic recovery by day +30/ toxicity/ overall survival 2yrs post-transplant/ event-free survival 2yrs post-transplant/ VOD/ incidence of infection. Incidence of: aGvHD by day +100/ cGvHD by day +365/ relapse 2yrs post-transplant [ Time Frame: 2 years after transplantation ] [ Designated as safety issue: No ]

Descriptive Information

Brief Title  ICMJEDose-Reduced Versus Standard Conditioning Prior Allo SCT for MDS/sAML Patients
Official Title  ICMJEDose-Reduced Versus Standard Conditioning Followed by Allogeneic Stem Cell Transplantation in Patients With MDS or sAML: A Randomised Phase III Study
Brief Summary

The present study is a multicenter, prospective phase III-study comparing dose-reduced versus standard conditioning followed by allogeneic stem cell transplantation from related or unrelated donors in patients with MDS or secondary AML.

The hypothesis is that dose-reduced conditioning will reduce the non-relapse mortality from 40% to 20% at one year after allogeneic stem cell transplantation.

Detailed Description 
Study PhasePhase III
Study Type  ICMJEInterventional
Study Design  ICMJETreatment, Randomized, Open Label, Parallel Assignment, Safety/Efficacy Study
Condition  ICMJE
  • Myelodysplastic Syndrome
  • Secondary Acute Myeloid Leukemia
Intervention  ICMJE
  • Procedure: Standard conditioning prior allo SCT

    Busilvex 12.8 mg/kg IBW i.v.

    • day -9: 0.8 mg/kg IBW x 4 (every 6 hours)
    • day -8: 0.8 mg/kg IBW x 4 (every 6 hours)
    • day -7: 0.8 mg/kg IBW x 4 (every 6 hours)
    • day -6: 0.8 mg/kg IBW x 4 (every 6 hours)

    OR

    Busulfan 16.0 mg/kg BW p.o.

    • day -9: 4.0 mg/kg BW
    • day -8: 4.0 mg/kg BW
    • day -7: 4.0 mg/kg BW
    • day -6: 4.0 mg/kg BW

    PLUS

    Cyclophosphamide 120 mg/kg BW i.v.

    • day -4: 60 mg/kg BW
    • day -3: 60 mg/kg BW
  • Procedure: Dose-reduced conditioning prior allo SCT

    Busilvex 6.4 mg/kg IBW i.v.

    • day -7: 0.8 mg/kg IBW x 4 (every 6 hours)
    • day -6: 0.8 mg/kg IBW x 4 (every 6 hours)

    OR

    Busulfan 8.0 mg/kg BW p.o.

    • day -7: 4.0 mg/kg BW
    • day -6: 4.0 mg/kg BW

    PLUS

    Fludarabine 5 x 30 mg/m^2 BS i.v.:

    • day -7: 30 mg/m^2 BS
    • day -6: 30 mg/m^2 BS
    • day -5: 30 mg/m^2 BS
    • day -4: 30 mg/m^2 BS
    • day -3: 30 mg/m^2 BS
Study Arms / Comparison Groups
  • A: Active Comparator
    Standard conditioning
    Intervention: Procedure: Standard conditioning prior allo SCT
  • B: Experimental
    Dose-reduced conditioning
    Intervention: Procedure: Dose-reduced conditioning prior allo SCT

Recruitment Information

Estimated Enrollment  ICMJE160
Estimated Completion DateMay 2013
Estimated Primary Completion DateMay 2012   (final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Disease: cytologically proven

    • primary or therapy related myelodysplastic syndrome (MDS) either as

      • refractory anaemia (RA) according FAB or RA with or without dysplasia according WHO
      • refractory anaemia with ringsideroblasts (RARS) according FAB or RARS with or without dysplasia according WHO
      • refractory anaemia with excess of blasts (RAEB) according FAB or RAEB I or RAEB II according WHO
      • refractory anaemia with excess of blast in transformation (RAEB-T) according FAB
      • CMML (dysplastic type) according WHO
    • or secondary acute myeloid leukaemia (sAML)
  • Blast count <20 percent in bone marrow with or without chemotherapy at time of transplantation
  • Patient eligible for standard and dose-reduced conditioning as per local guideline
  • Patient age 18-60 years if donor is a HLA-matched UNRELATED donor (HLA-A, HLA-B, HLA-DRB1 and HLA-DQB1) (one mismatch allowed)
  • Patient age 18-65 years if donor is a HLA-matched RELATED donor (HLA-A, HLA-B, HLA-DRB1 and HLA-DQB1)(one antigen-mismatch allowed)
  • no major organ dysfunction
  • written informed consent of the patient

Exclusion Criteria:

  • Blasts >20% in bone marrow at time of transplantation
  • no written informed consent
  • central nervous involvement
  • Severe irreversible renal, hepatic, pulmonary or cardiac disease, such as

    • total bilirubin, SGPT or SGOT > 2 times upper the normal level
    • Left ventricular ejection fraction <30%
    • creatinine clearance <30 ml/min
    • DLCO <35% and/or receiving supplementary continuous oxygen
  • Positive serology for HIV
  • pregnant or lactating women
  • patients with a life-expectancy of less than six months because of another debilitating disease
  • serious psychiatric or psychological disorders
  • invasive fungal infection at time of registration
GenderBoth
Ages18 Years to 65 Years
Accepts Healthy VolunteersNo
Contacts  ICMJE
Contact: Nicolaus Kroeger, Prof. Dr.+49-40-42803-5864nkroeger@uke.uni-hamburg.de
Contact: Marleen van Os+31-71 526 9720ebmtcto@lumc.nl
Location Countries  ICMJEGermany,   Italy,   Netherlands,   Russian Federation

Administrative Information

NCT ID  ICMJENCT00682396
Responsible PartyProf. N. Kroeger, European Group for Blood and Marrow Transplantation
Study ID Numbers  ICMJERICMAC, EBMT 42205525
Study Sponsor  ICMJEUniversitätsklinikum Hamburg-Eppendorf
Collaborators  ICMJEPierre Fabre Medicament
Investigators  ICMJE
Study Chair:Nicolaus Kröger, MDUniversity Medical Center Hamburg-Eppendorf, Germany
Study Chair:Theo de Witte, MDUniversity Hospital Nijmegen, The Netherlands
Principal Investigator:Axel R. Zander, MDUniversity Medical Center Hamburg-Eppendorf, Germany
Principal Investigator:Ghulam J Mufti, MDKing's College Hospital London, United Kingdom
Principal Investigator:Marie Robin, MDHopital Saint-Louis Paris, France
Principal Investigator:Hartmut Biersack, MDUniversity Hospital, Essen
Principal Investigator:Christoph Schmid, MDKlinikum Augsburg, Germany
Principal Investigator:Kathrin Haifa Al-Ali, MDUniversity Hospital Leipzig, Germany
Principal Investigator:Dietger Niederwieser, MDUniversity Hospital Leipzig, Germany
Principal Investigator:Francesco Onida, MDIRCCS Ospedale Maggiore di Milano, Italy
Principal Investigator:Alois Gratwohl, MDUniversity Horpital Basel, Switzerland
Principal Investigator:Tapani Ruutu, MDHelsinki University Central Hospital, Finland
Principal Investigator:Giorgio Lambertenghi Deliliers, MDIRCCS Ospedal Maggiore di Milano, Italy
Principal Investigator:Augustin Ferrant, MDCliniques Universitaires St. Luc Bruxelles, Belgium
Information Provided ByUniversitätsklinikum Hamburg-Eppendorf