NCT01062490

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
45

participants targeted

Target at P25-P50 for phase_2

Timeline
Completed

Started Nov 2004

Longer than P75 for phase_2

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

November 1, 2004

Completed
3.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2008

Completed
1.3 years until next milestone

Study Completion

Last participant's last visit for all outcomes

October 1, 2009

Completed
4 months until next milestone

First Submitted

Initial submission to the registry

February 3, 2010

Completed
1 day until next milestone

First Posted

Study publicly available on registry

February 4, 2010

Completed
Last Updated

February 4, 2010

Status Verified

February 1, 2010

Enrollment Period

3.7 years

First QC Date

February 3, 2010

Last Update Submit

February 3, 2010

Conditions

Myelodysplastic Syndrome

Keywords

TreosulfanMDSallogeneic stem cell transplantationleukemiaConditioning

Outcome Measures

Primary Outcomes (2)

  • 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

Study Arms (1)

Treosulfan

EXPERIMENTAL

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

Interventions

TreosulfanDRUG

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

Also known as: Ovastat
Treosulfan

Eligibility Criteria

Age18 Years - 60 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64)

You may qualify if:

  • 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

You may not qualify if:

  • '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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Helsinki University Central Hospital

Helsinki, 00029, Finland

Location

Related Publications (1)

  • Ruutu T, Volin L, Beelen DW, Trenschel R, Finke J, Schnitzler M, Holowiecki J, Giebel S, Markiewicz M, Uharek L, Blau IW, Kienast J, Stelljes M, Larsson K, Zander AR, Gramatzki M, Repp R, Einsele H, Stuhler G, Baumgart J, Mylius HA, Pichlmeier U, Freund M, Casper J. Reduced-toxicity conditioning with treosulfan and fludarabine in allogeneic hematopoietic stem cell transplantation for myelodysplastic syndromes: final results of an international prospective phase II trial. Haematologica. 2011 Sep;96(9):1344-50. doi: 10.3324/haematol.2011.043810. Epub 2011 Jun 9.

    PMID: 21659356DERIVED

MeSH Terms

Conditions

Myelodysplastic SyndromesLeukemia

Interventions

treosulfan

Condition Hierarchy (Ancestors)

Bone Marrow DiseasesHematologic DiseasesHemic and Lymphatic DiseasesNeoplasms by Histologic TypeNeoplasms

Study Officials

  • Tapani Ruutu, MD

    Biomedicum Helsinki 2 C, POB 705, Turkholmankatu 8 C, FIN-00029 HUS Helsinki, Finland

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY

Study Record Dates

First Submitted

February 3, 2010

First Posted

February 4, 2010

Study Start

November 1, 2004

Primary Completion

July 1, 2008

Study Completion

October 1, 2009

Last Updated

February 4, 2010

Record last verified: 2010-02

Locations

FI(1)