GvHD Prophylaxis in Unrelated Donor HCT: Randomized Trial Comparing PTCY Versus ATG (GRAPPA)

This is an interventional prevention trial for Graft Vs Host Disease focused on measuring Graft vs Host Disease, Peripheral Blood Stem Cell Transplantation, Cyclophsophamide, Anti-thymocyte globulin (rabbit) Read More

Inclusion Criteria:

• Signed written Informed Consent and able to understand the nature of the trial and the trial related procedures and to comply with them.
• Age ≥ 18 years.
• One of the following eligible diagnoses: AML in CR1 with intermediate or adverse risk genetic abnormalities (according to the ELN 2017 guidelines), or undefined risk. AML of any ELN risk category after hematological or molecular relapse, or with primary refractory disease. AML arising from myelodysplastic syndrome (MDS) or a myeloproliferative neoplasia, except if favourable genetic abnormalities (according to ELN 2017 guidelines) are present. Therapy-related myeloid neoplasia (t-MN), except if favourable genetic abnormalities (according to ELN 2017 guidelines) are present. MDS with intermediate risk, high risk or very high risk disease (according to the IPSS-R Score) regardless of treatment status. MDS/MPN and CMML-1/CMML-2 regardless of treatment status.
• The left ventricular ejection fraction (LVEF) was assessed ≥40% at last echocardiography.
• Transplantation with Peripheral Blood Stem Cells (PBSC) scheduled to be performed 4 to 14 days after date of randomization.
• The scheduled donor is unrelated to the patient, and matched or partially matched (with not more than one allele or antigen mismatch) at HLA-A, -B, -C, or -DRB1.
• Absence of pregnancy confirmed by highly sensitive pregnancy test for WOCBP. Test must not date back more than 3 days prior to randomization, or more than 3 days prior to start of conditioning, if it started before randomization.

Exclusion Criteria:

• Anamnestic intravenous or subcutaneous exposure to rabbit immunoglobin-preparations (e.g. Grafalon or Thymoglobulin)
• Known hypersensitivity to ATG-Grafalon or its excipients.
• Known hypersensitivity to cyclophosphamide, its metabolites or excipients.
• Prior allogeneic hematopoietic transplantation.
• Patients who receive supplementary continuous oxygen at the time of randomization.
• Symptomatic heart failure (NYHA ≥2) at the time of randomization.
• Uncontrolled viral, bacterial or fungal infection with progression or no clinical improvement at the time of randomization.
• Symptomatic cystitis or known obstruction of urine flow at the time of randomization.
• Breast-feeding women.
• WOCBP and fertile male patients unable or unwilling to follow highly effective contraception methods from enrollment to minimum six months after the last dose of the IMP.
• Simultaneous participation in another interventional clinical trial with an investigational medicinal product.