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

Sponsor
DKMS gemeinnützige GmbH (Other)
Overall Status
Recruiting
CT.gov ID
NCT05153226
Collaborator
(none)
540
16
2
53
33.8
0.6

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Anticipated Enrollment :
540 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Prevention
Official Title:
Graft vs Host Disease Prophylaxis in Unrelated Donor Transplantation: a Randomized Clinical Trial Comparing PTCY vs ATG (GRAPPA)
Actual Study Start Date :
Mar 2, 2022
Anticipated Primary Completion Date :
Aug 1, 2025
Anticipated Study Completion Date :
Aug 1, 2026

Arms and Interventions

Arm Intervention/Treatment
Experimental: Cyclophosphamide

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

Drug: Cyclophosphamide
50 mg/kg (AIBW) i.v. d+3, d+4 post transplant
Other Names:
  • all brands
  • Active Comparator: ATG

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

    Biological: ATG
    10 mg/kg i.v. d-3, d-2, d-1 pre-transplant
    Other Names:
  • ATG Grafalon
  • Outcome Measures

    Primary Outcome Measures

    1. Overall survival from HCT [1 year]

    2. Relapse- and Immunosuppression-free Survival (RIFS) [1 year after HCT]

    Secondary Outcome Measures

    1. GVHD-and relapse-free survival (GRFS) [1 year]

    2. Cumulative incidence of relapse [1 year]

    3. Cumulative incidence of non-relapse mortality [1 year]

    4. Cumulative incidences of acute and chronic GVHD [180 days and 2 years after HCT]

    5. Event-free survival [1 year]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Univeristätsklinikum Augsburg Augsburg Germany 86156
    2 Klinikum Chemnitz gGmbH Chemnitz Germany 09113
    3 Universitätsklinikum Dresden Dresden Germany 01307
    4 Universitätsklinikum Essen (AöR) Essen Germany 45147
    5 Universitätsklinikum Frankfurt Frankfurt am Main Germany 60595
    6 Universitätsklinikum Halle (Saale) Halle Germany 06120
    7 Universitätsklinikum des Saarlandes Homburg Germany 66421
    8 Universitätsklinikum Jena Jena Germany 07747
    9 Universitätsklinikum Schleswig-Holstein Lübeck Germany 23538
    10 Universitätsmedizin Mainz Mainz Germany 55131
    11 Universitätsmedizin Mannheim Mannheim Germany 68167
    12 Philipps Universität Marburg Marburg Germany 35043
    13 Universitätsklinikum Münster Münster Germany 48149
    14 Klinikum Nürnberg Nord Nürnberg Germany 90419
    15 Universitätsmedizin Rostock Rostock Germany 18057
    16 Universitätsklinikum Tübingen Tübingen Germany 72076

    Sponsors and Collaborators

    • DKMS gemeinnützige GmbH

    Investigators

    • Study Chair: Johannes Schetelig, Prof Dr med, Universitätsklinikum Dresden

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    DKMS gemeinnützige GmbH
    ClinicalTrials.gov Identifier:
    NCT05153226
    Other Study ID Numbers:
    • DKMS-21-01
    • 2021-000853-17
    First Posted:
    Dec 10, 2021
    Last Update Posted:
    Aug 22, 2022
    Last Verified:
    Aug 1, 2022
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by DKMS gemeinnützige GmbH
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Aug 22, 2022