Treosulfan Based Conditioning Myelodysplastic Syndrome (MDS)

Myelodysplastic Syndrome Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01062490
• Other study ID #: MC-FludT.8/MDS
• Status: Completed
• Phase: Phase 2
• First received: February 3, 2010
• Last updated: February 3, 2010
• Start date: November 2004
• Est. completion date: October 2009

Study information

• Verified date: February 2010
• Source: medac GmbH
• Contact: n/a
• Is FDA regulated: No
• Health authority: Finland: Finnish Medicines Agency
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 45
• Est. completion date: October 2009
• Est. primary completion date: July 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Myelodysplastic Syndrome
• Myelodysplastic Syndromes
• Preleukemia
• Syndrome

Intervention

Drug:
• Treosulfan
14 g/m2/d, day -6 to -4

Locations

Country	Name	City	State
Finland	Helsinki University Central Hospital	Helsinki

Sponsors (1)

Lead Sponsor	Collaborator
medac GmbH

Country where clinical trial is conducted

Finland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Efficacy: Evaluation of engraftment		4 years	Yes
Primary	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	Yes