Acute Myeloid Leukaemia
Conditions
Keywords
Treosulfan, Fludarabine, ATG, AML
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.
Interventions
DRUGTreosulfan
14 g/m²/d day -6 to -4
Sponsors
medac GmbH
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | 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
| Measure | 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 |
Countries
Germany
Outcome results
None listed