Treosulfan Based Conditioning Acute Myeloid Leukaemia (AML)

Phase 2

Completed

• Conditions: Acute Myeloid Leukaemia
• Interventions: Drug: Treosulfan

• Registration Number: NCT01063660
• Lead Sponsor: medac GmbH

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 AML.

The aim is to demonstrate a clinical benefit compared with historical data on intravenous busulfan (BusulfexTM, BusilvexTM), the only drug so far registered in the indication conditioning before allogeneic stem cell transplantation.

Detailed Description

Not available

Study Timeline

• Study Start: 2004-03
• Study Completion: 2007-07
• Status Verified: 2010-02
• Study First Submitted: 2010-02-03
• Study First Submitted QC: 2010-02-04
• Last Update Submitted: 2010-02-04
• Study First Posted: 2010-02-05
• Last Update Posted: 2010-02-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 75

Inclusion Criteria

• Patients with acute myeloid leukaemia (AML) according to WHO classification (> 20% myeloblasts in peripheral blood or bone marrow at initial diagnosis) with < 5% myeloblast in the bone marrow, 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: A, B, DRB1, DQB1.
• Target graft size (unmanipulated)
• bone marrow: 2 - 10 x 106 CD34+ cells/kg BW recipient or > 2 x 108 nucleated cells/kg BW recipient or
• peripheral blood: 4 - 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

• Therapy related secondary AML
• AML with t(8;21)(q22;q22) in CR1
• Acute promyelocytic leukaemia with t(15;17)(q22;q12) in CR1
• Secondary malignancies
• 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 day -6
• Non-co-operative behaviour or non-compliance
• Psychiatric diseases or conditions that might impair the ability to give informed consent

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treosulfan	Treosulfan	Patients with acute myeloid leukaemia (AML) according to WHO classification (\> 20% myeloblasts in peripheral blood or bone marrow at initial diagnosis) with \< 5% myeloblasts in the bone marrow, indicated for allogeneic transplantation

Primary Outcome Measures

Name	Time	Method
Efficacy - Evaluation of engraftment. Safety - Evaluation of the incidence of the following CTC grade 3 and 4 adverse events between day -6 and day +28 - hyperbilirubinemia and mucositis / stomatitis - veno-occlusive disease - seizures	3.5 years

Secondary Outcome Measures

Name	Time	Method
Efficacy - Evaluation of disease free survival (DFS) - Evaluation of overall survival (OS) - Evaluation of relapse incidence (RI) - Donor chimerism on day +28, +56 and +100. Safety - Evaluation of NRM on days +28 and +100	3.5 years

Trial Locations

Locations (1)

University of Rostock; 🇩🇪 Rostock, Germany