NCT01203228

Brief Summary

In this trial dose reduced conditioning is compared to standard conditioning followed by allogeneic stem cell transplantation from related or unrelated donors in patients with MDS or secondary AML. Conditioning is the very high dose chemotherapy treatment that is given in the days before the stem cell transplant. 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.

Trial Health

60
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
129

participants targeted

Target at P25-P50 for phase_3

Timeline
Completed

Started May 2004

Longer than P75 for phase_3

Geographic Reach
4 countries

14 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

May 1, 2004

Completed
6.4 years until next milestone

First Submitted

Initial submission to the registry

September 15, 2010

Completed
1 day until next milestone

First Posted

Study publicly available on registry

September 16, 2010

Completed
4.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2015

Completed
1 month until next milestone

Study Completion

Last participant's last visit for all outcomes

February 1, 2015

Completed
Last Updated

April 3, 2015

Status Verified

April 1, 2015

Enrollment Period

10.7 years

First QC Date

September 15, 2010

Last Update Submit

April 2, 2015

Conditions

Myelodysplastic SyndromesSecondary Acute Myeloid Leukemia

Keywords

Reduced Intensity conditioningMyeloablative conditionigAllogeneic stem cell transplantationMUD

Outcome Measures

Primary Outcomes (1)

  • non-relapse mortality

    every 6 months for safety and in the final analysis at one year after allogeneic stem cell transplantation

Secondary Outcomes (9)

  • organ related toxicity of conditioning

    every 6 months for safety and in the final analysis at day +30 after allogeneic stem cell transplantation

  • Incidence of aGVHD

    every 6 months for safety and in the final analysis at day +100 after allogeneic stem cell transplantation

  • incidence of cGVHD

    every 6 months for safety and in the final analysis at one year after allogeneic stem cell transplantation

  • overall survival

    every 6 months for safety and in the final analysis at 2 years after allogeneic stem cell transplantation

  • event-free survival

    every 6 months for safety and in the final analysis at 2 years after allogeneic stem cell transplantation

  • +4 more secondary outcomes

Study Arms (2)

A

ACTIVE COMPARATOR

Myeloablative conditioning

Other: Myeloablative conditioning

B

EXPERIMENTAL

Reduced Intensity Conditioning

Other: Reduced Intensity Conditioning

Interventions

Reduced Intensity ConditioningOTHER

Busilvex®: 6.4 mg/kg IBW i. v. day -7: 0.8 mg/kg IBW x 4 (2 hour infusion every 6 hours) day -6: 0.8 mg/kg IBW x 4 (2 hour infusion every 6 hours) or (if i.v.-application is not available) 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/m² BS i. v.: day -7: 30 mg/m² BS day -6: 30 mg/m² BS day -5: 30 mg/m² BS day -4: 30 mg/m² BS day -3: 30 mg/m² BS

Also known as: Myleran, Sulphabutin, Busulphan, Leucosulfan, Myeloleukon, Citosulfan, Mielevcin, Milecitan, Fludara, Beneflur, Fludura, FAMP, 2-Fluoro-ara-AMP
B
Myeloablative conditioningOTHER

Busilvex®: 12.8 mg/kg IBW i. v.; day -9: 0.8 mg/kg IBW x 4 (2 hour infusion every 6 hours) day -8: 0.8 mg/kg IBW x 4 (2 hour infusion every 6 hours) day -7: 0.8 mg/kg IBW x 4 (2 hour infusion every 6 hours) day -6: 0.8 mg/kg IBW x 4 (2 hour infusion every 6 hours) or (if i.v.-application is not available): 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

Also known as: Myleran, Sulphabutin, Busulphan, Leucosulfan, Myeloleukon, Citosulfan, Mielevcin, Milecitan, cyclophosphamide, Procytox, Cytoxan, Cyclophosphan, Cytophosphan, Claphene, Cyclostin, Endoxan
A

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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 anti¬gen-mismatch allowed):
  • No major organ dysfunction.
  • Written informed consent of the patient.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (14)

University Hospital

Cologne, Germany

Location

University Hospital

Düsseldorf, Germany

Location

Martin-Luther-Universität Halle-Wittenberg

Halle, Germany

Location

University Hospital Eppendorf

Hamburg, Germany

Location

University Hospital

Heidelberg, Germany

Location

UKSH Campus Kiel

Kiel, Germany

Location

University Hospital

Leipzig, Germany

Location

Universitätsklinikum Munster

Münster, Germany

Location

University Hospital

Tübingen, Germany

Location

Santi Antonio e Biagio

Alessandria, Italy

Location

Ospedale di Careggi

Florence, Italy

Location

Ospedale Maggiore di Milano

Milan, Italy

Location

Radboud University MC

Nijmegen, Netherlands

Location

SPb State I. Pavlov Medical University

Saint Petersburg, Russia

Location

Related Links

MeSH Terms

Conditions

Myelodysplastic Syndromes

Interventions

Busulfanfludarabine phosphateBone Marrow PurgingCyclophosphamide

Condition Hierarchy (Ancestors)

Bone Marrow DiseasesHematologic DiseasesHemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Butylene GlycolsGlycolsAlcoholsOrganic ChemicalsMesylatesAlkanesulfonatesAlkanesulfonic AcidsAlkanesHydrocarbons, AcyclicHydrocarbonsSulfonic AcidsSulfur AcidsSulfur CompoundsBlood Component RemovalTherapeuticsPhosphoramide MustardsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedPhosphoramidesOrganophosphorus Compounds

Study Officials

  • Nicolaus Kröger, MD

    Universitätsklinikum Hamburg-Eppendorf

    STUDY CHAIR

  • Axel R Zander, MD

    University Hospital 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

  • Kathrin Haifa Al-Ali, MD

    University Hospital Leipzig, Germany

    PRINCIPAL INVESTIGATOR

  • Dietger Niederwieser, MD

    University Hospital Leipzig, Germany

    PRINCIPAL INVESTIGATOR

  • Giorgio Lambertenghi Deliliers

    IRCCS Ospedale Maggiore of Milan, Italy

    PRINCIPAL INVESTIGATOR

  • Domink Heim, Prof.

    University Hospital, Basel, Switzerland

    PRINCIPAL INVESTIGATOR

  • Liisa Volin, MD

    Helsinki University Central Hospital, Finland

    PRINCIPAL INVESTIGATOR

  • Stefano Guidi, MD

    Careggi Hospital - Florence, Italy

    PRINCIPAL INVESTIGATOR

  • Augustin Ferrant, MD

    Cliniques Universitaires St. Luc Bruxelles, Belgium

    PRINCIPAL INVESTIGATOR

  • Afanasyer Boris

    SPB Pavlov Medical Univ, St. Petersburg, Russia

    PRINCIPAL INVESTIGATOR

  • Kai Hubel

    University of Cologne

    PRINCIPAL INVESTIGATOR

  • Peter Dreger

    Univ Hospital Heidelberg - Germany

    PRINCIPAL INVESTIGATOR

  • Martin Gramatzlle

    University Hospital Münster - Germany

    PRINCIPAL INVESTIGATOR

  • Gerhard Behre

    Martin-Luther-Universitaet Halle-Wittenberg - Germany

    PRINCIPAL INVESTIGATOR

  • Martin Gramatzlle

    Univ Hospital Kiel - Germany

    PRINCIPAL INVESTIGATOR

  • Allione Bernardino

    Santi Antonio E Biagio

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
NETWORK
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 15, 2010

First Posted

September 16, 2010

Study Start

May 1, 2004

Primary Completion

January 1, 2015

Study Completion

February 1, 2015

Last Updated

April 3, 2015

Record last verified: 2015-04

Locations

IT(3)DE(9)RU(1)NL(1)