Lanoracopan to Prevent Acute GVHD Following Haploidentical Peripheral Blood Stem Cell Transplantation: A Prospective Multicenter Single-Arm Exploratory Study
Lanoracopan for Prevention of Acute Graft-Versus-Host Disease After Haploidentical Peripheral Blood Stem Cell Transplantation: A Prospective, Multicenter, Single-Arm Exploratory Study
This is a prospective, multicenter, open-label, single-arm exploratory study. Thirty adult patients with hematologic malignancies who are scheduled to receive haploidentical peripheral blood stem-cell transplantation with myeloablative conditioning will be enrolled.
All participants will receive standard anti-thymocyte globulin (ATG, total 7.5 mg/kg), standard graft-versus-host-disease (GVHD) prophylaxis (calcineurin inhibitor + mycophenolate mofetil + short-course methotrexate), plus lanoracopan 200 mg twice daily from day +1 to day +90 after stem-cell infusion. Lanoracopan is an approved complement alternative-pathway inhibitor being used off-label for GVHD prevention in this trial. Mandatory antibiotic prophylaxis against encapsulated bacterial pathogens will be given.
The primary goal is to evaluate the safety of lanoracopan in this transplant setting, including adverse events / serious adverse events, neutrophil and platelet engraftment, graft-failure rate, and infectious complications. The key secondary objective is to explore the cumulative incidence of grade II-IV acute GVHD at day 100 post-transplant. Additional secondary outcomes include chronic GVHD, TA-TMA, 1-year overall survival, disease-free survival, cumulative incidence of relapse, and non-relapse mortality. Exploratory biomarker assessments will be performed on plasma and serum samples.
Participants will be followed for 1 year after transplantation. No control group is included in this exploratory study.
Aperçu de l'étude
Statut
Les conditions
Type d'étude
Inscription (Estimé)
Phase
- Phase 2
Contacts et emplacements
Coordonnées de l'étude
- Nom: LIMIN LIU, MD
- Numéro de téléphone: +86-512-6778183
- E-mail: Liminliu1006@163.com
Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
La description
Inclusion Criteria:
- Age 18-70 years, any gender.
- Diagnosed with hematologic malignancy according to WHO 2022 guidelines and eligible for allogeneic hematopoietic stem-cell transplantation.
- Scheduled to receive haploidentical peripheral blood stem-cell transplantation.
- Receive myeloablative conditioning regimen.
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
- Adequate major organ function: left-ventricular ejection fraction ≥50%; DLCO ≥50% predicted value; ALT/AST ≤3×ULN, total bilirubin ≤2×ULN; creatinine clearance ≥60 mL/min.
- Able to understand study requirements and provide written informed consent.
Exclusion Criteria:
- Prior allogeneic hematopoietic stem-cell transplantation.
- Active uncontrolled infection judged by investigator.
- Myocardial infarction or unstable angina within previous 6 months.
- Known hypersensitivity to lanoracopan or its excipients.
- Pregnant or breastfeeding female subjects.
- Concurrent participation in other investigational drug clinical trials with similar mechanism.
- Any other conditions that make the subject unsuitable for enrollment as judged by the investigator.
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: La prévention
- Répartition: N / A
- Modèle interventionnel: Affectation à un seul groupe
- Masquage: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
|
Expérimental: Lanoracopan Combined With ATG and Standard GVHD Prophylaxis
|
200 mg oral, twice daily, administered from post-transplant day +1 to day +90. Off-label use for prevention of acute graft-versus-host-disease. Total dose 7.5 mg/kg, administered intravenously from pre-transplant day -5 to day -2. Standard-dose calcineurin inhibitor (either cyclosporine or tacrolimus) as part of routine GVHD prophylaxis. Mycophenolate mofetil given per local center routine for GVHD prophylaxis. Short-course methotrexate for standard GVHD prophylaxis after allogeneic stem-cell transplantation. |
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Safety: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs); neutrophil and platelet engraftment; graft-failure rate; infectious complications
Délai: From study drug initiation (post-transplant day +1) up to 1 year after stem-cell transplantation
|
To evaluate the safety of lanoracopan for aGVHD prophylaxis. Assess the incidence and maximum grade of adverse events (AEs) and serious adverse events (SAEs) graded by CTCAE version 5.0; time to neutrophil engraftment, time to platelet engraftment; graft failure rate; incidence of infectious complications among participants. |
From study drug initiation (post-transplant day +1) up to 1 year after stem-cell transplantation
|
Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Cumulative incidence of grade II-IV acute graft-versus-host disease (aGVHD)
Délai: 100 days after stem-cell transplantation
|
Key secondary endpoint. Cumulative incidence of grade II-IV aGVHD at day 100 after haploidentical peripheral blood stem-cell transplantation, estimated by cumulative incidence function with non-relapse mortality as competing event. |
100 days after stem-cell transplantation
|
|
Cumulative incidence of chronic graft-versus-host disease (cGVHD)
Délai: Up to 1 year after stem-cell transplantation
|
Cumulative incidence of cGVHD within 1-year post-transplantation. |
Up to 1 year after stem-cell transplantation
|
|
One-year overall survival (OS), disease-free survival (DFS), cumulative incidence of relapse (CIR), non-relapse mortality (NRM)
Délai: Up to 1 year after stem-cell transplantation
|
Evaluate 1-year OS, 1-year DFS, 1-year CIR and 1-year NRM after haploidentical peripheral blood stem-cell transplantation. |
Up to 1 year after stem-cell transplantation
|
Collaborateurs et enquêteurs
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude (Estimé)
Achèvement primaire (Estimé)
Achèvement de l'étude (Estimé)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Réel)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
- Tumeurs par site
- Tumeurs
- Maladies hématologiques
- Maladies hémiques et lymphatiques
- Tumeurs hématologiques
- Mécanismes moléculaires d'action pharmacologique
- Inhibiteurs d'enzymes
- Peptides
- Acides aminés, peptides et protéines
- Protéines
- Produits chimiques organiques
- Composés hétérocycliques
- Composés hétérocycliques, 2 anneaux
- Composés hétérocycliques, anneau fusionné
- Acides gras
- Lipides
- Actions pharmacologiques
- Actions et utilisations chimiques
- Acides, acyclique
- Acides carboxyliques
- Composés polycycliques
- Anticorps
- Immunoglobulines
- Immunoprotéines
- Protéines sanguines
- Globulines sériques
- Globulines
- Macrolides
- Lactones
- Pterines
- Ptéridines
- Aminoptérine
- Composés macrocycliques
- Produits biologiques
- Mélanges complexes
- Peptides, cyclique
- Caproates
- Cyclosporines
- Sérums immunitaires
- Méthotrexate
- Acide mycophénolique
- Tacrolimus
- Cyclosporine
- Sérum antilymphocytaire
- Inhibiteurs de la calcineurine
Autres numéros d'identification d'étude
- 20261008093031021
Plan pour les données individuelles des participants (IPD)
Prévoyez-vous de partager les données individuelles des participants (DPI) ?
Description du régime IPD
Individual participant-level data (IPD) will not be shared with external researchers. This is a single-arm exploratory study sponsored by a hospital. Aggregated study results will be published in peer-reviewed journals and presented at academic conferences, but raw individual-level participant data cannot be released due to participant privacy protection and institutional data management requirements.
Informations sur les médicaments et les dispositifs, documents d'étude
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