Clinical trial NCT05153226: GvHD Prophylaxis in Unrelated Donor HCT: Randomized Trial Comparing PTCY Versus ATG
Official title: Graft vs Host Disease Prophylaxis in Unrelated Donor Transplantation: a Randomized Clinical Trial Comparing PTCY vs ATG (GRAPPA)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
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)
Lead sponsor: DKMS gemeinnützige GmbH
Sponsor class: OTHER
First posted: 2021-12-10
Enrollment: 640
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


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.

Primary outcomes:
measure: Overall survival
timeFrame: from randomization
measure: GVHD- and relapse-free survival (GRFS)
timeFrame: from HCT
Secondary outcomes:
measure: Overall survival
timeFrame: from HCT
measure: Relapse- and immunosuppression-free survival (RIFS)
timeFrame: from HCT
measure: Event-free survival
timeFrame: 1 year
measure: Cumulative incidence of relapse
timeFrame: 1 year
measure: Cumulative incidence of non-relapse mortality
timeFrame: 1 year
measure: Cumulative incidences of acute and chronic GVHD
timeFrame: 180 days and 2 years after HCT
Other outcomes:
Locations:
city: Aachen
country: Germany
facility: Uniklinik RWTH Aachen
city: Augsburg
country: Germany
facility: Univeristätsklinikum Augsburg
city: Chemnitz
country: Germany
facility: Klinikum Chemnitz gGmbH
city: Dortmund
country: Germany
facility: St.-Johannes-Hospital Dortmund
city: Dresden
country: Germany
facility: Universitätsklinikum Dresden
city: Düsseldorf
country: Germany
facility: Uniklinikum Düsseldorf
city: Essen
country: Germany
facility: Universitätsklinikum Essen (AöR)
city: Frankfurt am Main
country: Germany
facility: Universitätsklinikum Frankfurt
city: Halle
country: Germany
facility: Universitätsklinikum Halle (Saale)
city: Homburg
country: Germany
facility: Universitätsklinikum des Saarlandes
city: Jena
country: Germany
facility: Universitätsklinikum Jena
city: Kiel
country: Germany
facility: Universitätsklinikum Schleswig-Holstein
city: Köln
country: Germany
facility: Universitätsklinikum Köln
city: Lübeck
country: Germany
facility: Universitätsklinikum Schleswig-Holstein
city: Mainz
country: Germany
facility: Universitätsmedizin Mainz
city: Mannheim
country: Germany
facility: Universitätsmedizin Mannheim
city: Marburg
country: Germany
facility: Philipps Universität Marburg
city: Münster
country: Germany
facility: Universitätsklinikum Münster
city: Nürnberg
country: Germany
facility: Klinikum Nürnberg Nord
city: Rostock
country: Germany
facility: Universitätsmedizin Rostock
city: Stuttgart
country: Germany
facility: Robert-Bosch-Krankenhaus
city: Tübingen
country: Germany
facility: Universitätsklinikum Tübingen
city: Würzburg
country: Germany
facility: Universitätsklinikum Würzburg
Study officials:
affiliation: Universitätsklinikum Dresden
name: Johannes Schetelig, Prof Dr med
role: STUDY_CHAIR
References: