The present study will be 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.
ID
Source
Brief title
Condition
- Leukaemias
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
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.
Secondary outcome
Comparison of haematopoietic recovery by day +30 post transplant between two
arms.
* Comparison of toxicity of both regimens.
* Incidence of acute GVHD by day +100 and of chronic GVHD by day +365.
* Overall survival and event-free survival post-transplant at two years.
* Incidence of relapse post-transplant at two years.
* Comparison of VOD (veno-occlusive disease0 between the two arms.
* Comparison of infectious complications at one year and at two years after
transplantation.
* Comparison of quality of life between the treatment arms.
Background summary
Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal
haematological disorders, which are characterised by abnormal cellular
maturation resulting in cytopenias and a variable risk of progression to acute
leukaemia.
Currently allogeneic stem cell transplantation has been shown the most
effective treatment. However this treatment is accompanied by high treatment
related mortality. Recently, reduced intensity allogeneic stem cell
transplantation has been developed for patients with hematological
malignancies. However this treatment is especially employed in older patients
and in patients who are due to comorbidity, not eligible for allogeneic stem
cell transplantation after standard conditioning. Comparable studies are not
available yet
Study objective
The present study will be 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.
Study design
Prospective randomised phase III multi-center study.
Intervention
Arm A (standard conditioning):
Busulfan 4 mg/kg/day orally during 4 days or Busilvex 3.2 mg/kg/day
intravenously. during 4 days.
Cyclophosphamide 60 mg/kg/day intravenously during 2 days
Arm B (reduced intensity conditioning)
Busulfan 4 mg/kg/day orally during 2 days or Busilvex 3.2 mg/kg/day
intravenously during 2 days.
Fludarabine 30 mg/m2/day intravenously during 5 days
Study burden and risks
The therapy strategies to be checked in this protocol have * in short * the
following advantages and disadvantages:
Standard-Conditioning (Arm A):
* Advantage: Because of the intensity of the chemotherapy, less relapses after
allogeneic
transplantation are probably to be expected.
* Disadvantage: Due to the intensity of the chemotherapy, more therapy-related
complications, especially a higher number of treatment-related mortality, are
probable.
Dose-reduced Conditioning (Arm B):
* Advantage: Because of the less intensive chemotherapy, less therapy-related
side effects and a lower risk of therapy-related mortality are probable.
* Disadvantage: Maybe a higher relapse rate due to the lower intensity of the
chemotherapy.
University Medical Center, Department of Hematology
Nijmegen
Nederland
University Medical Center, Department of Hematology
Nijmegen
Nederland
Listed location countries
Age
Inclusion criteria
Cytogenetically proven MDS or sAML
Patient between 18 and 60 years of age in case of a HLA matched unrelated donor
Patient between 50 and 65 years of age in case of a HLA matched related donor
Exclusion criteria
Blasts >20% in bone marrow at time of transplantation
Patients with a life-expectancy of less than six months because of another debilitating disease
Invasive fungal infection at time of registration
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL18050.091.07 |