Matched Unrelated vs. Haploidentical Donor for Allogeneic Stem Cell Transplantation in Patients With Acute Leukemia

Matched Unrelated vs. Haploidentical Donor for Allogeneic Stem Cell Transplantation in Patients With Acute Leukemia With Identical GVHD Prophylaxis - A Randomized Prospective European Trial.

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%.

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.

Inclusion Criteria

1. 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.
2. Patients age: 18 - 70 years at time of inclusion (female and male).
3. Patients understand and voluntarily sign an informed consent form.
4. ECOG ≤ 2.
5. 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.
6. Females/Males who agree to comply with the applicable contraceptive requirements of the protocol.

Exclusion Criteria

1. 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

2. Positive serology for HIV.

3. Pregnant or lactating women (positive serum pregnancy test).

4. Age < 18 and ≥ 71 years.

5. Uncontrolled invasive fungal infection at time of screening (baseline).

6. Serious psychiatric or psychological disorders.

7. Participation in another study with ongoing use of unlicensed investigational product from 28 days before study enrollment.

8. Uncontrolled severe autoimmune disease or uncontrolled other malignancy.

9. Availability of an HLA-identical sibling as donor source.