GvHD Prophylaxis in Unrelated Donor HCT: Randomized Trial Comparing PTCY Versus ATG (GRAPPA)
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ClinicalTrials.gov Identifier: NCT05153226 |
Recruitment Status :
Recruiting
First Posted : December 10, 2021
Last Update Posted : December 15, 2023
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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 |
---|---|---|
Graft Vs Host Disease Peripheral Blood Stem Cell Transplantation AML MDS MDS/MPN CMML | Drug: Cyclophosphamide Biological: ATG | Phase 3 |
Study Type : | Interventional (Clinical Trial) |
Estimated 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 : | March 2, 2022 |
Estimated Primary Completion Date : | August 2025 |
Estimated Study Completion Date : | August 2026 |
Arm | Intervention/treatment |
---|---|
Experimental: Cyclophosphamide
Cyclophosphamide 50 mg/kg (AIBW) i.v. d+3, d+4 post transplant
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Drug: Cyclophosphamide
50 mg/kg (AIBW) i.v. d+3, d+4 post transplant
Other Name: all brands |
Active Comparator: ATG
ATG Grafalon 10 mg/kg i.v. d-3, d-2, d-1 pre-transplant
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Biological: ATG
10 mg/kg i.v. d-3, d-2, d-1 pre-transplant
Other Name: ATG Grafalon |
- Overall survival from HCT [ Time Frame: 1 year ]
- Relapse- and Immunosuppression-free Survival (RIFS) [ Time Frame: 1 year after HCT ]
- GVHD-and relapse-free survival (GRFS) [ Time Frame: 1 year ]
- Cumulative incidence of relapse [ Time Frame: 1 year ]
- Cumulative incidence of non-relapse mortality [ Time Frame: 1 year ]
- Cumulative incidences of acute and chronic GVHD [ Time Frame: 180 days and 2 years after HCT ]
- Event-free survival [ Time Frame: 1 year ]
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Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05153226
Contact: Sarah Trost, MSc | +49 351 210 798 ext 28 | grappa@dkms.de |
Study Chair: | Johannes Schetelig, Prof Dr med | Universitätsklinikum Dresden |
Responsible Party: | DKMS gemeinnützige GmbH |
ClinicalTrials.gov Identifier: | NCT05153226 |
Other Study ID Numbers: |
DKMS-21-01 2021-000853-17 ( EudraCT Number ) |
First Posted: | December 10, 2021 Key Record Dates |
Last Update Posted: | December 15, 2023 |
Last Verified: | July 2023 |
Studies a U.S. FDA-regulated Drug Product: | No |
Studies a U.S. FDA-regulated Device Product: | No |
Graft vs Host Disease Peripheral Blood Stem Cell Transplantation Cyclophsophamide Anti-thymocyte globulin (rabbit) |
Graft vs Host Disease Immune System Diseases Cyclophosphamide Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs |
Antirheumatic Agents Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Myeloablative Agonists |