Patients with acute myeloid leukaemia (AML) or myelodysplastic syndrome (MDS) considered ineligible to standard conditioning therapies prior to allogeneic stem cell transplantation. MedDRA version: 20.0 Level: PT Classification code 10000881 Term: Acute myeloid leukaemia (in remission) System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: LLT Classification code 10028534 Term: Myelodysplastic syndrome NOS System Organ Cla
Conditions
Interventions
Trade Name: Ovastat 1000 (Treosulfan injection)
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: Treosulfan
CAS Number: 299-75-2
Other descriptive name: Treograft
Concentrati
Sponsors
medac Gesellschaft für klinische Spezialpräparate mbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients with acute myeloid leukaemia acc. to WHO, 2008 (AML in complete remission at transplant, i.e. blast counts 2 [according to Sorror et al., 2005] 2. Availability of an HLA-identical sibling donor (MRD) or HLA-identical unrelated donor (MUD). Donor selection is based on molecular high resolution typing (4 digits) of class II alleles of the DRB1 and DQB1 gene loci and molecular (at least) low resolution typing (2 digits) of class I alleles (i.e., antigens) of the HLA- A, B, and C gene loci. In case no class I and class II completely identical donor (10 out of 10 gene loci) can be identified, one antigen disparity (class I) and/or one allele disparity (class II) between patient and donor are acceptable. Conversely, disparity of two antigens (irrespective of the involved gene loci) cannot be accepted. These definitions for the required degree of histocompatibility apply to the selection of related as well as unrelated donors. 3. Adult patients of both gender, 18 – 70 years of age 4. Karnofsky Index = 60 % 5. Written informed consent 6. Men capable of reproduction and women of childbearing potential must be willing to consent to using a highly effective method of birth control such as condoms, implants, injectables, combined oral contraceptives, IUDs, sexual abstinence or vasectomised partner while on treatment and for at least 6 months thereafter. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 787 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 173
Exclusion criteria
Exclusion criteria: 1. Patients with acute promyelocytic leukaemia with t(15;17)(q22;q12) and in CR1 2. Patients considered contra-indicated for allogeneic HSCT due to severe concomitant illness (within three weeks prior to scheduled day -6): - patients with severe renal impairment like patients on dialysis or prior renal transplantation or S-creatinine > 3.0 x ULN or calculated creatinine-clearance 3 x ULN or ALT / AST > 5 x ULN 3. Active malignant involvement of the CNS 4. HIV-positivity, active non-controlled infectious disease under treatment (no decrease of CRP or PCT) including active viral liver infection 5. Previous allogeneic HSCT 6. Pleural effusion or ascites > 1.0 L 7. Pregnancy or lactation 8. Known hypersensitivity to treosulfan, busulfan and/or related ingredients 9. Participation in another experimental drug trial within 4 weeks prior to day –6 of the protocol 10. Non-cooperative behaviour or non-compliance 11. Psychiatric diseases or conditions that might compromise the ability to give informed consent
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To show at least non-inferiority of treosulfan-based conditioning to reduced-intensity conditioning therapy based on i.v. busulfan and to compare the associated safety profiles. The aim of the study is to compare event-free survival within 2 years after transplantation between treosulfan-based conditioning and busulfan-based conditioning. Events are defined as relapse of disease, graft failure or death (whatever occurs first).;Secondary Objective: 1. Comparative evaluation of incidence of CTC grade III/IV mucositis between day -6 and day +28. 2. Comparative evaluation of overall survival (OS) and cumulative incidence of relapse (RI), non-relapse mortality (NRM) and transplantation-related mortality (TRM) within 2 years after transplantation. 3. Comparative evaluation of day +28 conditional cumulative incidence of engraftment. 4. Comparative evaluation of day +28 and day +100 incidence of complete donor-type chimerism. 5. Comparative evaluation of cumulative incidence of acute and chronic GvHD within 2 years after transplantation. 6. Comparative evaluation of incidence of other CTC grade III/IV adverse events between day -6 and day +28. ;Primary end point(s): Event-free survival (EFS) within 2 years after transplantation measured from time of start of HSCT (= day 0) to time of event. Events are defined as relapse of disease, graft failure or death (whatever occurs first). ;Timepoint(s) of evaluation of this end point: 2 years after start of transplantation. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): CTC grade III/IV mucositis between day -6 and day +28. Overall survival, relapse, non-relapse mortality and transplantation-related mortality within 2 years after transplantation. Engraftment until day +28. Complete donor-type chimerism of day +28 and day +100. Acute and chronic GvHD within 2 years after transplantation. ;Timepoint(s) of evaluation of this end point: Please refer to E.5.2 | — |
Countries
Finland, France, Germany, Hungary, Italy, Poland
Contacts
Public ContactClinical Research
medac Gesellschaft für klinische Spezialpräparate mbH
Outcome results
None listed