Treosulfan Based Conditioning Acute Myeloid Leukaemia (AML)

Sponsor

medac GmbH (Industry)

Overall Status

Completed

CT.gov ID

NCT01063660

Collaborator

(none)

Enrollment

Location

Arm

Duration (Months)

1.9

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 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.

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukaemia	Drug: Treosulfan	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

75 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Supportive Care

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 Acute Myeloid Leukaemia

Study Start Date :

Mar 1, 2004

Actual Study Completion Date :

Jul 1, 2007

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: 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

Drug: Treosulfan

14 g/m²/d day -6 to -4

Other Names:

Ovastat

Outcome Measures

Primary Outcome Measures

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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