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

AML Clinical Trial

— GRAPPA  

Official title:

Graft vs Host Disease Prophylaxis in Unrelated Donor Transplantation: a Randomized Clinical Trial Comparing PTCY vs ATG (GRAPPA)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05153226
• Other study ID #: DKMS-21-01
• Secondary ID: 2021-000853-17
• Status: Recruiting
• Phase: Phase 3
• Start date: March 2, 2022
• Est. completion date: August 2026

Study information

• Verified date: July 2023
• Source: DKMS gemeinnützige GmbH
• Contact: Sarah Trost, MSc
• Phone: +49 351 210 798
• Email: grappa[@]dkms.de
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 540
• Est. completion date: August 2026
• Est. primary completion date: August 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

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

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

Locations

Country	Name	City	State
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 des Saarlandes	Homburg
Germany	Universitätsklinikum Jena	Jena
Germany	Universitätsklinikum Schleswig-Holstein	Kiel
Germany	Universitätsklinikum Köln	Köln
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	Nürnberg
Germany	Universitätsmedizin Rostock	Rostock
Germany	Robert-Bosch-Krankenhaus	Stuttgart
Germany	Universitätsklinikum Tübingen	Tübingen
Germany	Universitätsklinikum Würzburg	Würzburg

Sponsors (1)

Lead Sponsor	Collaborator
DKMS gemeinnützige GmbH

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival from HCT		1 year
Primary	Relapse- and Immunosuppression-free Survival (RIFS)		1 year after HCT
Secondary	GVHD-and relapse-free survival (GRFS)		1 year
Secondary	Cumulative incidence of relapse		1 year
Secondary	Cumulative incidence of non-relapse mortality		1 year
Secondary	Cumulative incidences of acute and chronic GVHD		180 days and 2 years after HCT
Secondary	Event-free survival		1 year