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

Tracking Information

Start Date ^ICMJE	May 2004
Estimated Primary Completion Date	May 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 History	Complete 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 ^ICMJE	Dose-Reduced Versus Standard Conditioning Prior Allo SCT for MDS/sAML Patients
Official Title ^ICMJE	Dose-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 Phase	Phase III
Study Type ^ICMJE	Interventional
Study Design ^ICMJE	Treatment, 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 ^ICMJE

160

Estimated Completion Date

May 2013

Estimated Primary Completion Date

May 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

Gender

Both

Ages

18 Years to 65 Years

Accepts Healthy Volunteers

Contacts ^ICMJE

Contact: Nicolaus Kroeger, Prof. Dr.	+49-40-42803-5864	nkroeger@uke.uni-hamburg.de
Contact: Marleen van Os	+31-71 526 9720	ebmtcto@lumc.nl

Location Countries ^ICMJE

Germany, Italy, Netherlands, Russian Federation

Administrative Information

NCT ID ^ICMJE

NCT00682396

Responsible Party

Prof. N. Kroeger, European Group for Blood and Marrow Transplantation

Study ID Numbers ^ICMJE

RICMAC, EBMT 42205525

Study Sponsor ^ICMJE

Universitätsklinikum Hamburg-Eppendorf

Collaborators ^ICMJE

Pierre Fabre Medicament

Investigators ^ICMJE

Study Chair:	Nicolaus Kröger, MD	University Medical Center Hamburg-Eppendorf, Germany
Study Chair:	Theo de Witte, MD	University Hospital Nijmegen, The Netherlands
Principal Investigator:	Axel R. Zander, MD	University Medical Center Hamburg-Eppendorf, Germany
Principal Investigator:	Ghulam J Mufti, MD	King's College Hospital London, United Kingdom
Principal Investigator:	Marie Robin, MD	Hopital Saint-Louis Paris, France
Principal Investigator:	Hartmut Biersack, MD	University Hospital, Essen
Principal Investigator:	Christoph Schmid, MD	Klinikum Augsburg, Germany
Principal Investigator:	Kathrin Haifa Al-Ali, MD	University Hospital Leipzig, Germany
Principal Investigator:	Dietger Niederwieser, MD	University Hospital Leipzig, Germany
Principal Investigator:	Francesco Onida, MD	IRCCS Ospedale Maggiore di Milano, Italy
Principal Investigator:	Alois Gratwohl, MD	University Horpital Basel, Switzerland
Principal Investigator:	Tapani Ruutu, MD	Helsinki University Central Hospital, Finland
Principal Investigator:	Giorgio Lambertenghi Deliliers, MD	IRCCS Ospedal Maggiore di Milano, Italy
Principal Investigator:	Augustin Ferrant, MD	Cliniques Universitaires St. Luc Bruxelles, Belgium

Information Provided By

Universitätsklinikum Hamburg-Eppendorf

Source: http://clinicaltrials.gov/