Treosulfan Based Conditioning Myelodysplastic Syndrome (MDS)

Sponsor

medac GmbH (Industry)

Overall Status

Completed

CT.gov ID

NCT01062490

Collaborator

(none)

Enrollment

Location

Arm

Duration (Months)

0.8

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Myelodysplastic Syndrome	Drug: Treosulfan	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

45 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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)

Study Start Date :

Nov 1, 2004

Actual Primary Completion Date :

Jul 1, 2008

Actual Study Completion Date :

Oct 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treosulfan 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 14 g/m2/d, day -6 to -4 Other Names: Ovastat

Arm

Intervention/Treatment

Experimental: Treosulfan

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

14 g/m2/d, day -6 to -4

Other Names:

Ovastat

Outcome Measures

Primary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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