GRAPPA

Phase 3

Active, not recruiting

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

• Registration Number: 2023-510441-24-00
• Lead Sponsor: DKMS Group gGmbH

Brief Summary

One of the key elements to improve allogeneic HCT is the administration of optimized

conditioning treatment including immunosuppressive drugs to facilitate engraftment, prevent

GVHD and induce tolerance of donor immune cells.

Specifically, the goal of this trial is to investigate the impact of PTCY versus ATG Grafalon ®

as part of a conditioning treatment for alloHCT on overall survival (OS) and on graft-versus host

disease-free and relapse-free survival (GRFS).

Information on the investigational drugs provided by these two endpoints will enable the

scientific community a comprehensive assessment of the two approaches for alloHCT.

Detailed Description

Not available

Study Timeline

• Study First Posted: 2024-09-20
• Last Update Posted: 2024-09-20

Recruitment & Eligibility

• Status: Ongoing, recruitment ended
• Sex: Not specified
• Target Recruitment: 640

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 (see Section 24.3). − Age ≥ 18 years. − One of the following eligible diagnoses: - AML in CR1 with intermediate or adverse risk genetic abnormalities (according to the ELN 2022 guidelines1), or undefined risk. - AML of any ELN risk category after hematological or molecular relapse0F a, or with primary refractory disease. - AML arising from myelodysplastic syndrome (MDS) or a myeloproliferative neoplasia, except if favourable genetic abnormalities (according to ELN 2022 guidelines1) are present. - Therapy-related myeloid neoplasia (t-MN), except if favourable genetic abnormalities (according to ELN 2022 guidelines1) are present. - MDS with intermediate risk, high risk or very high risk disease according to the IPSS-R Score or MDS with moderate high, high, or very high risk disease according to the IPSS-M Score2 regardless of treatment status. - MDS/MPN and CMML-1/CMML-2 according to WHO 20223 regardless of treatment status. − The left ventricular ejection fraction (LVEF) was ≥40% at last assessment. − Planned transplantation with Peripheral Blood Stem Cells (PBSC). − Transplantation 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 (see Section 17.7). 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 (see Section 17.7). − Simultaneous participation in another interventional clinical trial with an investigational medicinal product.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
(1) overall survival (OS) from randomization, and (2) graft-versus-host disease-free and relapse-free survival (GRFS) from time of transplantation.		(1) overall survival (OS) from randomization, and (2) graft-versus-host disease-free and relapse-free survival (GRFS) from time of transplantation.

Secondary Outcome Measures

Name	Time	Method
− Overall survival from HCT. − Relapse- and immunosuppression-free survival (RIFS) from HCT. − Event-free survival (EFS) from HCT. − Cumulative incidences of relapse from HCT. − Cumulative incidences of non-relapse mortality (NRM) from HCT, etc. (s.protocol section 10.2).		− Overall survival from HCT. − Relapse- and immunosuppression-free survival (RIFS) from HCT. − Event-free survival (EFS) from HCT. − Cumulative incidences of relapse from HCT. − Cumulative incidences of non-relapse mortality (NRM) from HCT, etc. (s.protocol section 10.2).

Trial Locations

Locations (24)

Universitaetsklinikum Aachen AöR; 🇩🇪 Aachen, Germany

Philipps-Universitaet Marburg; 🇩🇪 Marburg, Germany

Universitaet Des Saarlandes; 🇩🇪 Homburg, Germany

Universitaetsklinikum Schleswig-Holstein AöR; 🇩🇪 Luebeck, Germany

Universitaetsklinikum Duesseldorf AöR; 🇩🇪 Duesseldorf, Germany

Klinikum Nuernberg; 🇩🇪 Nuremberg, Germany

Universitaetsklinikum Wuerzburg AöR; 🇩🇪 Wuerzburg, Germany

Universitaetsklinikum Jena KöR; 🇩🇪 Jena, Germany

Staedtisches Klinikum Karlsruhe gGmbH; 🇩🇪 Karlsruhe, Germany

Rostock University Medical Center; 🇩🇪 Rostock, Germany

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Universitaetsklinikum Aachen AöR

🇩🇪Aachen, Germany

Edgar Jost

Site contact

+4902418080732

ejost@ukaachen.de