Treosulfan Based Conditioning Acute Myeloid Leukaemia (AML)

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Acute Myeloid Leukaemia

Intervention / Treatment
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* Drug: Treosulfan


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treosulfan<br>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<br>* 14 g/m²/d day -6 to -4<br>* Other names: Ovastat;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Treosulfan, Fludarabine, ATG, AML