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.
Studieöversikt
Status
Betingelser
Studietyp
Inskrivning (Beräknad)
Fas
- Fas 2
Kontakter och platser
Studiekontakt
- Namn: LIMIN LIU, MD
- Telefonnummer: +86-512-6778183
- E-post: Liminliu1006@163.com
Deltagandekriterier
Urvalskriterier
Åldrar som är berättigade till studier
Tar emot friska volontärer
Kön som är behöriga för studier
Beskrivning
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.
Studieplan
Hur är studien utformad?
Designdetaljer
- Primärt syfte: Förebyggande
- Tilldelning: N/A
- Interventionsmodell: Enskild gruppuppgift
- Maskning: Ingen (Open Label)
Vapen och interventioner
Deltagargrupp / Arm |
Intervention / Behandling |
|---|---|
|
Experimentell: 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. |
Vad mäter studien?
Primära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
|---|---|---|
|
Safety: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs); neutrophil and platelet engraftment; graft-failure rate; infectious complications
Tidsram: 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
|
Sekundära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
|---|---|---|
|
Cumulative incidence of grade II-IV acute graft-versus-host disease (aGVHD)
Tidsram: 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)
Tidsram: 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)
Tidsram: 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
|
Samarbetspartners och utredare
Studieavstämningsdatum
Studera stora datum
Studiestart (Beräknad)
Primärt slutförande (Beräknad)
Avslutad studie (Beräknad)
Studieregistreringsdatum
Först inskickad
Först inskickad som uppfyllde QC-kriterierna
Första postat (Faktisk)
Uppdateringar av studier
Senaste uppdatering publicerad (Faktisk)
Senaste inskickade uppdateringen som uppfyllde QC-kriterierna
Senast verifierad
Mer information
Termer relaterade till denna studie
Ytterligare relevanta MeSH-villkor
- Neoplasmer efter plats
- Neoplasmer
- Hematologiska sjukdomar
- Hemiska och lymfsjukdomar
- Hematologiska neoplasmer
- Molekylära mekanismer för farmakologisk verkan
- Enzyminhibitorer
- Peptider
- Aminosyror, peptider och proteiner
- Proteiner
- Organiska kemikalier
- Heterocykliska föreningar
- Heterocykliska föreningar, 2-ring
- Heterocykliska föreningar, smältring
- Fettsyror
- Lipider
- Farmakologiska åtgärder
- Kemiska åtgärder och användningar
- Syror, acykliska
- Karboxylsyror
- Polycykliska föreningar
- Antikroppar
- Immunglobuliner
- Immunoproteiner
- Blodproteiner
- Serumglobuliner
- Globuliner
- Makrolider
- Laktoner
- Pteriner
- Pteridiner
- Aminopterin
- Makrocykliska föreningar
- Biologiska produkter
- Komplexa blandningar
- Peptider, cykliska
- Caproates
- Cyklosporiner
- Immunsera
- Metotrexat
- Mykofenolsyra
- Takrolimus
- Cyklosporin
- Antimfocytserum
- Calcineurin-hämmare
Andra studie-ID-nummer
- 20261008093031021
Plan för individuella deltagardata (IPD)
Planerar du att dela individuella deltagardata (IPD)?
IPD-planbeskrivning
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.
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