Myelodysplastic Syndrome
Conditions
Keywords
Treosulfan, MDS, allogeneic stem cell transplantation, leukemia, Conditioning
Brief summary
This is a multicenter, multinational, non-randomized, non-controlled open-label phase II trial to evaluate the safety and efficacy of treosulfan in a combination regimen with fludarabine as conditioning therapy prior to allogeneic stem cell transplantation (SCT) in patients with MDS. The aim is to demonstrate a clinical benefit compared to historical data with intravenous busulfan.
Interventions
DRUGTreosulfan
14 g/m2/d, day -6 to -4
Sponsors
medac GmbH
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
1. Patients with myelodysplastic syndrome, (MDS) according to WHO classification (\< 20 % myeloblasts in peripheral blood or bone marrow at initial diagnosis) indicated for allogeneic transplantation 2. Availability of an HLA-identical sibling donor (MRD) or HLA-identical unrelated donor (MUD) HLA-identity defined by the following markers: HLA-A, -B, -DRB1, DQB1. 3. Target graft size (unmanipulated) bone marrow: 2 to 10 x 106 CD34+ cells/kg BW recipient or at least 2 x 108 nucleated cells /kg BW or peripheral blood: 4 to 10 x 106 CD34+ cells/kg BW recipient 4. Age \> 18 and \< 60 years 5. Karnofsky Index \> 80 % 6. Adequate contraception in female patients of child-bearing potential 7. Written informed consent
Exclusion criteria
1. 'Secondary' or therapy-related MDS with known history of exposure to cytotoxic alkylating drugs and/or radiation therapy 2. Previous AML-induction therapy with more than two courses (e.g. in case of blast excess) 3. Previous allogeneic transplantation 4. Severe concomitant illnesses / medical conditions (e.g. impaired respiratory and/or cardiac function) 5. Known and manifested malignant involvement of the CNS 6. Active infectious disease 7. HIV- positivity or active hepatitis infection 8. Impaired liver function (Bilirubin \> upper normal limit; Transaminases \> 3.0 x upper normal limit) 9. Impaired renal function (Creatinine-clearance \< 60 ml/min; Serum Creatinine \> 1.5 x upper normal limit). 10. Pleural effusion or ascites \> 1.0 L 11. Pregnancy or lactation 12. Known hypersensitivity to treosulfan and/or fludarabine 13. Participation in another experimental drug trial within 4 weeks before study 14. Non-co-operative behaviour or non-compliance 15. Psychiatric diseases or conditions that might impair the ability to give informed consent
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Efficacy: Evaluation of engraftment | 4 years |
| Safety: Evaluation of CTC grade 3 and 4 adverse events between Day -6 and Day +28: hyperbilirubinemia and mucositis/stomatitis, veno-occlusive disease, seizures | 4 years |
Countries
Finland
Outcome results
None listed