Clinical Phase III Trial Treosulfan-based Conditioning Versus Reduced-intensity Conditioning (RIC)

Inclusion Criteria:

1. Patients with acute myeloid leukaemia acc. to WHO, 2008 (AML in complete remission attransplant, i.e. blast counts < 5 % in bone marrow) or myelodysplastic syndrome acc.to WHO, 2008 (MDS with blast counts < 20 % in bone marrow during disease history)indicated for allogeneic haematopoietic progenitor cell transplantation but consideredto be at increased risk for standard conditioning therapies according to the followingcriteria:

• patients aged ≥ 50 years at transplant and / or

• patients with a HCT-CI score > 2 [acc. 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) ofclass II alleles of the DRB1 and DQB1 gene loci and molecular (at least) lowresolution typing (2 digits) of class I alleles (i.e., antigens) of the HLA- A, B, andC gene loci. In case, no class I and class II completely identical donor (10 out of 10gene loci) can be identified, one antigen disparity (class I) and/or one alleledisparity (class II) between patient and donor are acceptable. Conversely, disparityof two antigens (irrespective of the involved gene loci) cannot be accepted. Thesedefinitions for the required degree of histocompatibility apply to the selection ofrelated as well as of unrelated donors.

3. Adult patients of both gender, age 18 - 70 years

4. Karnofsky Index ≥ 60 %

5. Written informed consent

6. Men capable of reproduction and women of childbearing potential must be willing toconsent to using a highly effective method of birth control such as condoms, implants,injectables, combined oral contraceptives, IUDs, sexual abstinence or vasectomisedpartner while on treatment and for at least 6 months thereafter

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 concomitantillness (within three weeks prior to scheduled day -6):

• patients with severe renal impairment like patients on dialysis or prior renaltransplantation or S-creatinine > 3.0 x ULN or calculated creatinine-clearance < 60 ml/min

• patients with severe pulmonary impairment, DLCOsb (Hb-adjusted)/or FEV1 < 50 % orsevere dyspnoea at rest or requiring oxygen supply

• patients with severe cardiac impairment diagnosed by echocardiography and LVEF < 40 %

• patients with severe hepatic impairment indicated by hyperbilirubinaemia > 3 xULN or ALT / AST > 5 x ULN

3. Active malignant involvement of the CNS

4. HIV-positivity, active non-controlled infectious disease under treatment (no decreaseof 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 theprotocol

10. Non-cooperative behaviour or non-compliance

11. Psychiatric diseases or conditions that might compromise the ability to give informedconsent