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.

Study Overview

• Status: Not yet recruiting
• Conditions: Hematologic Malignancies; Acute Graft-Versus-Host Disease; Haploidentical Peripheral Blood Stem Cell Transplantation
• Intervention / Treatment: Drug: Lanoracopan; Drug: Anti-thymocyte globulin (ATG); Drug: Calcineurin inhibitor (Cyclosporine or Tacrolimus); Drug: Mycophenolate mofetil (MMF); Drug: Methotrexate

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: LIMIN LIU, MD; Phone Number: +86-512-6778183; Email: Liminliu1006@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age 18-70 years, any gender.
2. Diagnosed with hematologic malignancy according to WHO 2022 guidelines and eligible for allogeneic hematopoietic stem-cell transplantation.
3. Scheduled to receive haploidentical peripheral blood stem-cell transplantation.
4. Receive myeloablative conditioning regimen.
5. Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
6. 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.
7. Able to understand study requirements and provide written informed consent.

Exclusion Criteria:

1. Prior allogeneic hematopoietic stem-cell transplantation.
2. Active uncontrolled infection judged by investigator.
3. Myocardial infarction or unstable angina within previous 6 months.
4. Known hypersensitivity to lanoracopan or its excipients.
5. Pregnant or breastfeeding female subjects.
6. Concurrent participation in other investigational drug clinical trials with similar mechanism.
7. Any other conditions that make the subject unsuitable for enrollment as judged by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Lanoracopan Combined With ATG and Standard GVHD Prophylaxis

Drug: Lanoracopan; 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.; Drug: Anti-thymocyte globulin (ATG); Total dose 7.5 mg/kg, administered intravenously from pre-transplant day -5 to day -2.; Drug: Calcineurin inhibitor (Cyclosporine or Tacrolimus); Standard-dose calcineurin inhibitor (either cyclosporine or tacrolimus) as part of routine GVHD prophylaxis.; Drug: Mycophenolate mofetil (MMF); Mycophenolate mofetil given per local center routine for GVHD prophylaxis.; Drug: Methotrexate; Short-course methotrexate for standard GVHD prophylaxis after allogeneic stem-cell transplantation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs); neutrophil and platelet engraftment; graft-failure rate; infectious complications	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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative incidence of grade II-IV acute graft-versus-host disease (aGVHD)	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)	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)	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

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Soochow University

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: November 4, 2026
• First Submitted That Met QC Criteria: November 4, 2026
• First Posted (Actual): November 9, 2026

Study Record Updates

• Last Update Posted (Actual): November 9, 2026
• Last Update Submitted That Met QC Criteria: November 4, 2026
• Last Verified: November 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Hematologic Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Fatty Acids; Lipids; Pharmacologic Actions; Chemical Actions and Uses; Acids, Acyclic; Carboxylic Acids; Polycyclic Compounds; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Macrolides; Lactones; Pterins; Pteridines; Aminopterin; Macrocyclic Compounds; Biological Products; Complex Mixtures; Peptides, Cyclic; Caproates; Cyclosporins; Immune Sera; Methotrexate; Mycophenolic Acid; Tacrolimus; Cyclosporine; Antilymphocyte Serum; Calcineurin Inhibitors
• Other Study ID Numbers: 20261008093031021

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD Plan Description

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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No