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

NCT05153226 | Active Not Recruiting Phase 3 DMC

• 2 other identifiers: DKMS-21-012021-000853-17
• Study Type: interventional
• Target: 640
• Locations: 1 country
• Sites: 23

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.

Conditions

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

Keywords

Graft vs Host Disease; Peripheral Blood Stem Cell Transplantation; Cyclophsophamide; Anti-thymocyte globulin (rabbit)

Outcome Measures

Primary Outcomes (2)

• Overall survival

  from randomization

• GVHD- and relapse-free survival (GRFS)

  from HCT

Secondary Outcomes (6)

• Overall survival

  from HCT

• Relapse- and immunosuppression-free survival (RIFS)

  from HCT

• Event-free survival

  1 year

• Cumulative incidence of relapse

  1 year

• Cumulative incidence of non-relapse mortality

  1 year

Study Arms (2)

Cyclophosphamide

EXPERIMENTAL

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

Drug: Cyclophosphamide

ATG

ACTIVE COMPARATOR

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

Biological: ATG

Interventions

Cyclophosphamide DRUG

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

Also known as: all brands

Cyclophosphamide

ATG BIOLOGICAL

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

Also known as: ATG Grafalon

ATG

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• DKMS gemeinnützige GmbH: lead

Study Sites (23)

Uniklinik RWTH Aachen

Aachen, 52074, Germany

Location

Univeristätsklinikum Augsburg

Augsburg, 86156, Germany

Location

Klinikum Chemnitz gGmbH

Chemnitz, 09113, Germany

Location

Universitätsklinikum Köln

Cologne, 50937, Germany

Location

St.-Johannes-Hospital Dortmund

Dortmund, 44137, Germany

Location

Universitätsklinikum Dresden

Dresden, 01307, Germany

Location

Uniklinikum Düsseldorf

Düsseldorf, 40225, Germany

Location

Universitätsklinikum Essen (AöR)

Essen, 45147, Germany

Location

Universitätsklinikum Frankfurt

Frankfurt am Main, 60595, Germany

Location

Universitätsklinikum Halle (Saale)

Halle, 06120, Germany

Location

Universitätsklinikum des Saarlandes

Homburg, 66421, Germany

Location

Universitätsklinikum Jena

Jena, 07747, Germany

Location

Universitätsklinikum Schleswig-Holstein

Kiel, 24105, Germany

Location

Universitätsklinikum Schleswig-Holstein

Lübeck, 23538, Germany

Location

Universitätsmedizin Mainz

Mainz, 55131, Germany

Location

Universitätsmedizin Mannheim

Mannheim, 68167, Germany

Location

Philipps Universität Marburg

Marburg, 35043, Germany

Location

Universitätsklinikum Münster

Münster, 48149, Germany

Location

Klinikum Nürnberg Nord

Nuremberg, 90419, Germany

Location

Universitätsmedizin Rostock

Rostock, 18057, Germany

Location

Robert-Bosch-Krankenhaus

Stuttgart, 70376, Germany

Location

Universitätsklinikum Tübingen

Tübingen, 72076, Germany

Location

Universitätsklinikum Würzburg

Würzburg, 97080, Germany

Location

MeSH Terms

Conditions

Graft vs Host Disease

Interventions

Cyclophosphamide

Condition Hierarchy (Ancestors)

Immune System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Johannes Schetelig, Prof Dr med

  Universitätsklinikum Dresden

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 26, 2021
• First Posted: December 10, 2021
• Study Start: March 2, 2022
• Primary Completion: June 1, 2025
• Study Completion (Estimated): December 1, 2026
• Last Updated: December 20, 2024

Record last verified: 2024-12

Locations

DE (23)