NCT05153226: GRAPPA

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

Active, enrolled Phase 3 Last updated 18 December 2024

What this trial tests

Phase 3 trial testing Cyclophosphamide in Graft Vs Host Disease in 640 participants. Participants enrolled and being followed up; not accepting new ones.

Timeline

2 March 2022

Primary endpoint
1 June 2025

1 December 2026

Quick facts

Lead sponsor	DKMS gemeinnützige GmbH
Phase	Phase 3
Status	Active, enrolled
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	prevention
Enrollment	640
Start date	2 March 2022
Primary completion	1 June 2025
Estimated completion	1 December 2026
Sites	23 locations across Germany

Drugs / interventions tested

• Cyclophosphamide (cyclophosphamide) — full drug profile →
• ATG — full drug profile →

Conditions studied

• Graft Vs Host Disease — all drugs for Graft Vs Host Disease →
• Peripheral Blood Stem Cell Transplantation — all drugs for Peripheral Blood Stem Cell Transplantation →
• AML — all drugs for AML →
• MDS — all drugs for MDS →

Sponsor

DKMS gemeinnützige GmbH — full company profile →

Who can join

18 and older, any sex, with Graft Vs Host Disease or Peripheral Blood Stem Cell Transplantation. Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• Overall survival
  Time frame: from randomization
• GVHD- and relapse-free survival (GRFS)
  Time frame: from HCT

Sponsor's own description

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.

Publications & conference data

5 peer-reviewed publications reference this trial (live from Europe PMC):

1. Post-Transplant Cyclophosphamide-Based Graft-Versus-Host Disease Prophylaxis Attenuates Disparity in Outcomes Between Use of Matched or Mismatched Unrelated Donors.
   Shaffer BC, Gooptu M, DeFor TE, Maiers M, et al · · 2024 · cited 59× · PMID 39018507 · DOI 10.1200/jco.24.00184
2. Immunopathogenic mechanisms and modulatory approaches to graft-versus-host disease prevention in acute myeloid leukaemia.
   Pang Y, Holtzman NG. · · 2023 · cited 3× · PMID 37353287 · DOI 10.1016/j.beha.2023.101475
3. Novel approaches to acute graft-versus-host disease prevention.
   Watkins B, Qayed M. · · 2023 · cited 2× · PMID 38066861 · DOI 10.1182/hematology.2023000426
4. Posttransplant cyclophosphamide in HLA-matched peripheral blood transplantation: what's next?
   Curtis DJ, Hill GR. · · 2026 · PMID 41411147 · DOI 10.1182/blood.2025030416
5. Post-transplant cyclophosphamide improves survival compared to antithymocyte globulin in HLA-mismatched unrelated donor stem cell transplantation.
   Bordat J, Kaphan E, Robin M, Xhaard A, et al · · 2026 · PMID 40874329 · DOI 10.3324/haematol.2024.287157