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

NCT ID: NCT05153226

Last Updated: 2024-12-20

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 640 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-03-02
• Study Completion Date: 2026-12-31

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.

Conditions

Graft Vs Host Disease; Peripheral Blood Stem Cell Transplantation; AML; MDS; MDS/MPN; CMML

Keywords

Graft vs Host Disease; Peripheral Blood Stem Cell Transplantation; Cyclophsophamide; Anti-thymocyte globulin (rabbit)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Cyclophosphamide

Cyclophosphamide 50 mg/kg (AIBW) i.v. d+3, d+4 post transplant

Group Type: EXPERIMENTAL

Cyclophosphamide

Intervention Type: DRUG

50 mg/kg (AIBW) i.v. d+3, d+4 post transplant

ATG

ATG Grafalon 10 mg/kg i.v. d-3, d-2, d-1 pre-transplant

Group Type: ACTIVE_COMPARATOR

ATG

Intervention Type: BIOLOGICAL

10 mg/kg i.v. d-3, d-2, d-1 pre-transplant

Interventions

Cyclophosphamide

50 mg/kg (AIBW) i.v. d+3, d+4 post transplant

Intervention Type: DRUG

ATG

10 mg/kg i.v. d-3, d-2, d-1 pre-transplant

Intervention Type: BIOLOGICAL

Other Intervention Names

all brands; ATG Grafalon

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

DKMS gemeinnützige GmbH

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Johannes Schetelig, Prof Dr med

Role: STUDY_CHAIR

Universitätsklinikum Dresden

Locations

Uniklinik RWTH Aachen

Aachen, , Germany

Univeristätsklinikum Augsburg

Augsburg, , Germany

Klinikum Chemnitz gGmbH

Chemnitz, , Germany

Universitätsklinikum Köln

Cologne, , 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 des Saarlandes

Homburg, , Germany

Universitätsklinikum Jena

Jena, , Germany

Universitätsklinikum Schleswig-Holstein

Kiel, , Germany

Universitätsklinikum Schleswig-Holstein

Lübeck, , Germany

Universitätsmedizin Mainz

Mainz, , Germany

Universitätsmedizin Mannheim

Mannheim, , Germany

Philipps Universität Marburg

Marburg, , Germany

Universitätsklinikum Münster

Münster, , Germany

Klinikum Nürnberg Nord

Nuremberg, , Germany

Universitätsmedizin Rostock

Rostock, , Germany

Robert-Bosch-Krankenhaus

Stuttgart, , Germany

Universitätsklinikum Tübingen

Tübingen, , Germany

Universitätsklinikum Würzburg

Würzburg, , Germany

Countries

Germany

Other Identifiers

2021-000853-17

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

DKMS-21-01

Identifier Type: -

Identifier Source: org_study_id