Overview
Primary objective of this open label, two-arm, multicenter, multinational, randomized trial is to compare anti-leukemic activity of allogeneic stem cell transplantation for patients with acute leukemia in complete remission between a 10/10 HLA matched unrelated donor and a haploidentical donor.
The hypothesis: Haploidentical stem cell transplantation with post cyclophosphamide induces a stronger anti-leukemic activity in comparison to 10/10 HLA matched unrelated donor and reduces the risk of relapse at 2 years after stem cell transplantation by 10%.
Description
Secondary objectives are to assess and compare the safety and efficacy of study treatments therapy in both study arms on non-relapse mortality (NRM), relapse-free survival (RFS), Overall survival (OS), QOL, toxicity, development of acute and chronic GvDH as well as engraftment and chimerism and impact of measurable residual disease.
Eligibility
Inclusion Criteria
- Acute Myeloid Leukemia (AML) intermediate or high risk according to ELN or Acute Lymphoblastic Leukemia (ALL) high risk according to ESMO guidelines in 1. CR or AML/ALL in 2. CR, or high risk MDS (according to IPSS-R) in 1. CR or 2. CR.
- Patients age: 18 - 70 years at time of inclusion (female and male).
- Patients understand and voluntarily sign an informed consent form.
- ECOG ≤ 2.
- 10/10 HLA-matched unrelated donor and haploidentical (≥ 5/10 and ≤ 8/10 HLA) relative matched donor available at least 4 weeks after completion of induction and/or consolidation therapy.
- Females/Males who agree to comply with the applicable contraceptive requirements of the protocol.
Exclusion Criteria
- Severe renal, hepatic, pulmonary or cardiac disease, such as:
- total bilirubin, SGPT or SGOT > 3 times upper the normal level
- left ventricular ejection fraction < 30 %
- creatinine clearance < 30 ml/min
- DLCO < 35 % and/or receiving supplementary continuous oxygen
- Positive serology for HIV.
- Pregnant or lactating women (positive serum pregnancy test).
- Age < 18 and ≥ 71 years.
- Uncontrolled invasive fungal infection at time of screening (baseline).
- Serious psychiatric or psychological disorders.
- Participation in another study with ongoing use of unlicensed investigational product from 28 days before study enrollment.
- Uncontrolled severe autoimmune disease or uncontrolled other malignancy.
- Availability of an HLA-identical sibling as donor source.