Treosulfan Based Conditioning Myelodysplastic Syndrome (MDS)

Study Overview
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Brief Summary
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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.

Official Title
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Clinical Phase II Trial to Evaluate the Safety and Efficacy of Treosulfan Based Conditioning Prior to Allogeneic Haematopoietic Stem Cell Transplantation in Patients With Myelodysplastic Syndrome (MDS)

Conditions
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Myelodysplastic Syndrome

Intervention / Treatment
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* Drug: Treosulfan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with myelodysplastic syndrome, (MDS) according to WHO classification (< 20 % myeloblasts in peripheral blood or bone marrow at initial diagnosis) indicated for allogeneic transplantation 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. 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 Age > 18 and < 60 years Karnofsky Index > 80 % Adequate contraception in female patients of child-bearing potential Written informed consent Exclusion Criteria: 'Secondary' or therapy-related MDS with known history of exposure to cytotoxic alkylating drugs and/or radiation therapy Previous AML-induction therapy with more than two courses (e.g. in case of blast excess) Previous allogeneic transplantation Severe concomitant illnesses / medical conditions (e.g. impaired respiratory and/or cardiac function) Known and manifested malignant involvement of the CNS Active infectious disease HIV- positivity or active hepatitis infection Impaired liver function (Bilirubin > upper normal limit; Transaminases > 3.0 x upper normal limit) Impaired renal function (Creatinine-clearance < 60 ml/min; Serum Creatinine > 1.5 x upper normal limit). Pleural effusion or ascites > 1.0 L Pregnancy or lactation Known hypersensitivity to treosulfan and/or fludarabine Participation in another experimental drug trial within 4 weeks before study Non-co-operative behaviour or non-compliance Psychiatric diseases or conditions that might impair the ability to give informed consent

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treosulfan<br>Patients with myelodysplastic syndrome, (MDS) according to WHO classification (< 20 % myeloblasts in peripheral blood or bone marrow at initial diagnosis) indicated for allogeneic transplantation | Drug: Treosulfan<br>* 14 g/m2/d, day -6 to -4<br>* Other names: Ovastat;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Treosulfan, MDS, allogeneic stem cell transplantation, leukemia, Conditioning