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

Phase 3

Active, not recruiting

• Conditions: MDS/MPN; Graft Vs Host Disease; CMML; Peripheral Blood Stem Cell Transplantation; AML; MDS
• Interventions: Biological: ATG; Drug: Cyclophosphamide

• Registration Number: NCT05153226
• Lead Sponsor: DKMS gemeinnützige GmbH

Brief Summary

Post-transplantation cyclophosphamide (PTCY) has become increasingly popular in the haploidentical HCT setting because it overcomes the HLA-mismatch barrier and levels GVHD risk. This advantage may also prove useful in the context of unrelated donor (UD) transplantation. GVHD prophylaxis for matched unrelated donor hematopoietic cell transplantation (alloHCT) in Europe is mainly conducted with ATG. Still, the burden of acute and chronic GVHD and especially of relapse remains high with both approaches for GVHD prevention.

PTCY has not been tested against the current standard ATG for GvHD prophylaxis in large randomized trials. The goal of this trial is to compare the outcomes of PTCY and ATG for patients receiving unrelated donor PBSCT. PTCY-based prophylaxis promises to have beneficial net effects on immune reconstitution, GVHD and disease control, and thus might impact on patient survival.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-11-26
• Study First Submitted QC: 2021-12-09
• Study First Posted: 2021-12-10
• Study Start: 2022-03-02
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-18
• Last Update Posted: 2025-03-25
• Primary Completion: 2025-06
• Study Completion: 2026-12

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 640

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ATG	ATG	ATG Grafalon 10 mg/kg i.v. d-3, d-2, d-1 pre-transplant
Cyclophosphamide	Cyclophosphamide	Cyclophosphamide 50 mg/kg (AIBW) i.v. d+3, d+4 post transplant

Primary Outcome Measures

Name	Time	Method
Overall survival	from randomization
GVHD- and relapse-free survival (GRFS)	from HCT

Secondary Outcome Measures

Name	Time	Method
Overall survival	from HCT
Relapse- and immunosuppression-free survival (RIFS)	from HCT
Event-free survival	1 year
Cumulative incidence of relapse	1 year
Cumulative incidence of non-relapse mortality	1 year
Cumulative incidences of acute and chronic GVHD	180 days and 2 years after HCT

Trial Locations

Locations (22)

Universitätsklinikum des Saarlandes; 🇩🇪 Homburg, Germany

Uniklinik RWTH Aachen; 🇩🇪 Aachen, Germany

Univeristätsklinikum Augsburg; 🇩🇪 Augsburg, Germany

Klinikum Chemnitz gGmbH; 🇩🇪 Chemnitz, Germany

St.-Johannes-Hospital Dortmund; 🇩🇪 Dortmund, Germany

Universitätsklinikum Dresden; 🇩🇪 Dresden, Germany

Uniklinikum Düsseldorf; 🇩🇪 Düsseldorf, Germany

Universitätsklinikum Essen (AöR); 🇩🇪 Essen, Germany

Universitätsklinikum Frankfurt; 🇩🇪 Frankfurt am Main, Germany

Universitätsklinikum Halle (Saale); 🇩🇪 Halle, Germany

Universitätsklinikum Jena; 🇩🇪 Jena, Germany

Universitätsklinikum Schleswig-Holstein; 🇩🇪 Lübeck, Germany

Universitätsklinikum Köln; 🇩🇪 Köln, Germany

Universitätsmedizin Mainz; 🇩🇪 Mainz, Germany

Universitätsmedizin Mannheim; 🇩🇪 Mannheim, Germany

Philipps Universität Marburg; 🇩🇪 Marburg, Germany

Universitätsklinikum Münster; 🇩🇪 Münster, Germany

Klinikum Nürnberg Nord; 🇩🇪 Nürnberg, Germany

Universitätsmedizin Rostock; 🇩🇪 Rostock, Germany

Robert-Bosch-Krankenhaus; 🇩🇪 Stuttgart, Germany

Universitätsklinikum Tübingen; 🇩🇪 Tübingen, Germany

Universitätsklinikum Würzburg; 🇩🇪 Würzburg, Germany