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.
Studieoversikt
Status
Forhold
Studietype
Registrering (Antatt)
Fase
- Fase 2
Kontakter og plasseringer
Studiekontakt
- Navn: LIMIN LIU, MD
- Telefonnummer: +86-512-6778183
- E-post: Liminliu1006@163.com
Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
Tar imot friske frivillige
Kjønn som er kvalifisert for studier
Beskrivelse
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
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Forebygging
- Tildeling: N/A
- Intervensjonsmodell: Enkeltgruppeoppdrag
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
|
Eksperimentell: 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. |
Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Safety: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs); neutrophil and platelet engraftment; graft-failure rate; infectious complications
Tidsramme: 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
|
Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Cumulative incidence of grade II-IV acute graft-versus-host disease (aGVHD)
Tidsramme: 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)
Tidsramme: 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)
Tidsramme: 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
|
Samarbeidspartnere og etterforskere
Studierekorddatoer
Studer hoveddatoer
Studiestart (Antatt)
Primær fullføring (Antatt)
Studiet fullført (Antatt)
Datoer for studieregistrering
Først innsendt
Først innsendt som oppfylte QC-kriteriene
Først lagt ut (Faktiske)
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Sist bekreftet
Mer informasjon
Begreper knyttet til denne studien
Ytterligere relevante MeSH-vilkår
- Neoplasmer etter nettsted
- Neoplasmer
- Hematologiske sykdommer
- Hemic og lymfatiske sykdommer
- Hematologiske neoplasmer
- Molekylære mekanismer for farmakologisk virkning
- Enzymhemmere
- Peptider
- Aminosyrer, peptider og proteiner
- Proteiner
- Organiske kjemikalier
- Heterocykliske forbindelser
- Heterocykliske forbindelser, 2-ring
- Heterocykliske forbindelser, smeltet ringen
- Fettsyrer
- Lipider
- Farmakologiske handlinger
- Kjemiske handlinger og bruk
- Syrer, acyklisk
- Karboksylsyrer
- Polysykliske forbindelser
- Antistoffer
- Immunoglobuliner
- Immunoproteiner
- Blodproteiner
- Serumglobuliner
- Globuliner
- Makrolider
- Laktoner
- Pteriner
- Pteridiner
- Aminopterin
- Makrosykliske forbindelser
- Biologiske produkter
- Komplekse blandinger
- Peptider, syklisk
- Caproates
- Cyclosporins
- Immunsera
- Metotreksat
- Mykofenolsyre
- Takrolimus
- Syklosporin
- Antilymfocyttserum
- Calcineurin-hemmere
Andre studie-ID-numre
- 20261008093031021
Plan for individuelle deltakerdata (IPD)
Planlegger du å dele individuelle deltakerdata (IPD)?
IPD-planbeskrivelse
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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