Clinical trial NCT01203228: Dose-reduced Versus Standard Conditioning in MDS/sAML
Official title: Dose-reduced Versus Standard Conditioning Followed by Allogeneic Stem Cell Transplantation in Patients With MDS or sAML: A Randomised Phase III Study (RICMAC)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Myelodysplastic Syndromes
Secondary Acute Myeloid Leukemia
Keywords: Reduced Intensity conditioning
Myeloablative conditionig
Allogeneic stem cell transplantation
MUD
Lead sponsor: European Society for Blood and Marrow Transplantation
Sponsor class: NETWORK
Collaborators: name: Pierre Fabre Medicament
First posted: 2010-09-16
Enrollment: 129
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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 anti¬gen-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.

Primary outcomes:
measure: non-relapse mortality
timeFrame: every 6 months for safety and in the final analysis at one year after allogeneic stem cell transplantation
Secondary outcomes:
measure: organ related toxicity of conditioning
timeFrame: every 6 months for safety and in the final analysis at day +30 after allogeneic stem cell transplantation
measure: Incidence of aGVHD
timeFrame: every 6 months for safety and in the final analysis at day +100 after allogeneic stem cell transplantation
measure: incidence of cGVHD
timeFrame: every 6 months for safety and in the final analysis at one year after allogeneic stem cell transplantation
measure: overall survival
timeFrame: every 6 months for safety and in the final analysis at 2 years after allogeneic stem cell transplantation
measure: event-free survival
timeFrame: every 6 months for safety and in the final analysis at 2 years after allogeneic stem cell transplantation
measure: cumulative incidence of relapse
timeFrame: every 6 months for safety and in the final analysis at 2 years after allogeneic stem cell transplantation
measure: VOD
timeFrame: every 6 months for safety and in the final analysis at day +100 after allogeneic stem cell transplantation
measure: infection incidence
timeFrame: every 6 months for safety and in the final analysis at day +100, 1 year and 2 years after allogeneic stem cell transplantation
measure: Haematopoeitic recovery
timeFrame: every 6 months for safety and in the final analysis at day +30 after allogeneic stem cell transplantation
Other outcomes:
Locations:
city: Düsseldorf
country: Germany
facility: University Hospital
city: Halle
country: Germany
facility: Martin-Luther-Universität Halle-Wittenberg
city: Hamburg
country: Germany
facility: University Hospital Eppendorf
city: Heidelberg
country: Germany
facility: University Hospital
city: Kiel
country: Germany
facility: UKSH Campus Kiel
city: Köln
country: Germany
facility: University Hospital
city: Leipzig
country: Germany
facility: University Hospital
city: Munster
country: Germany
facility: Universitätsklinikum Munster
city: Tübingen
country: Germany
facility: University Hospital
city: Alessandria
country: Italy
facility: Santi Antonio e Biagio
city: Firenze
country: Italy
facility: Ospedale di Careggi
city: Milano
country: Italy
facility: Ospedale Maggiore di Milano
city: Nijmegen
country: Netherlands
facility: Radboud University MC
city: St. Petersburg
country: Russian Federation
facility: SPb State I. Pavlov Medical University
Study officials:
affiliation: Universitätsklinikum Hamburg-Eppendorf
name: Nicolaus Kröger, MD
role: STUDY_CHAIR
affiliation: University Hospital Hamburg-Eppendorf, Germany
name: Axel R Zander, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: King's College Hospital London, United Kingdom
name: Ghulam J Mufti, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hopital Saint-Louis Paris, France
name: Marie Robin, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital Leipzig, Germany
name: Kathrin Haifa Al-Ali, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital Leipzig, Germany
name: Dietger Niederwieser, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: IRCCS Ospedale Maggiore of Milan, Italy
name: Giorgio Lambertenghi Deliliers
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital, Basel, Switzerland
name: Domink Heim, Prof.
role: PRINCIPAL_INVESTIGATOR
affiliation: Helsinki University Central Hospital, Finland
name: Liisa Volin, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Careggi Hospital - Florence, Italy
name: Stefano Guidi, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Cliniques Universitaires St. Luc Bruxelles, Belgium
name: Augustin Ferrant, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: SPB Pavlov Medical Univ, St. Petersburg, Russia
name: Afanasyer Boris
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Cologne
name: Kai Hubel
role: PRINCIPAL_INVESTIGATOR
affiliation: Univ Hospital Heidelberg - Germany
name: Peter Dreger
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital Münster - Germany
name: Martin Gramatzlle
role: PRINCIPAL_INVESTIGATOR
affiliation: Martin-Luther-Universitaet Halle-Wittenberg - Germany
name: Gerhard Behre
role: PRINCIPAL_INVESTIGATOR
affiliation: Univ Hospital Kiel - Germany
name: Martin Gramatzlle
role: PRINCIPAL_INVESTIGATOR
affiliation: Santi Antonio E Biagio
name: Allione Bernardino
role: PRINCIPAL_INVESTIGATOR
References: