Belimumab for Treatment of cGVHD Following Allo-HCT

NCT05604742 | Withdrawn Phase 1

• 1 other identifier: cGVHD202210310
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Given the role of B cells in the pathophysiology of chronic graft versus host disease (GvHD), the association between elevated BAFF levels post-transplant in abnormal B-cell homeostasis and chronic GvHD, and the efficacy of belimumab in the inhibition of soluble human B lymphocyte stimulator protein (BAFF) signaling, these proof-of-principle findings support the rational for use of belimumab as treatment of chronic GvHD.The investigators propose a pilot and feasibility study to assess the safety and tolerability, as well as preliminary efficacy, of belimumab a treatment of cGvHD following allogeneic hematopoietic cell transplantation (alloHCT). The investigators' central hypothesis is that belimumab will be well tolerated and have a favorable effect on chronic GvHD,and we explored therapeutic dosage of belimumab.

Conditions

cGVHD

Keywords

cGVHD; Resistance; belimumab

Outcome Measures

Primary Outcomes (1)

• Overall response rate of chronic GvHD after belimumab treatment

  cGVHD grade according NIH

  approximately 6 months

Secondary Outcomes (1)

• Duration of response rate of chronic GvHD after belimumab treatment

  12 months

Other Outcomes (2)

• Safety and tolerability of belimumab as treatment of chronic GvHD

  approximately 12 months

• Overall survival

  24 months

Study Arms (3)

Low-dose group of Belimumab

EXPERIMENTAL

Belimumab 1mg/kg com combined with conventional therapy

Drug: Belimumab (Benlysta)

High-dose group of Belimumab

EXPERIMENTAL

Belimumab 4mg/kg com combined with conventional therapy

Drug: Belimumab (Benlysta)

Control group

NO INTERVENTION

conventional therapy

Interventions

Belimumab (Benlysta) DRUG

Belimumab will be administered intravenously every 2 weeks for 3 cycles and then every 4 weeks for a total of 5 cycles

High-dose group of Belimumab; Low-dose group of Belimumab

Eligibility Criteria

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

You may qualify if:

• to 65years old 2.Newly diagnosed, moderate or severe chronic GvHD according to the 2014 NIH Consensus Criteria, requiring systemic immunosuppression 3.Karnofsky performance status greater than or equal to 60% 4.History of prior alloHSCT; any donors, conditioning regimens and graft sources are allowed 5.Newly diagnosed moderate or severe chronic Graft versus Host Disease (GvHD) (according to the 2014 NIH Consensus Criteria, requiring systemic immunosuppression 6.History of prior allogeneic Hematopoietic Stem Cell Transplant (HSCT) (any donors, conditioning regimens and graft sources are allowed).
• Stable doses of other immunosuppressive medications (e.g., calcineurin inhibitors, mycophenolate mofetil, rapamune, etc.) with no dose increase in the 2 weeks prior to study treatment initiation. Doses may be adjusted for trough levels.
• Patients tested positive for autoantibodies (ANA titer ≥1:80) and high BAFF levels (plasma concentration ≥15ng/ml).
• Laboratory parameters as defined below: Serum creatinine less than or equal to 2.0 x ULN AST and ALT less than or equal to 3 x ULN (less than or equal to 5 x ULN if unequivocal liver GvHD) Total bilirubin less than or equal to 3 x ULN 10.Ability to understand and willingness to sign a written informed consent fo

You may not qualify if:

• Relapsed or progressive malignant disease (other than minimal residual disease)
• History of other malignant diseases, including post-transplant lymphoproliferative disease
• Rituximab or other anti-B cell-specific antibodies were used in the past 3 months.
• Uncontrolled infections (including prior aspergillosis) not responsive to antibiotics, antiviral medicines, or antifungal medicines
• Donor lymphocyte transfusion for donor chimeric relapse or loss.
• Any other reason at the discretion of the investigators and documented in the medical record that may raise concerns about the subject safety or ability to participate on this study -

Sponsors & Collaborators

• xuna: lead

Study Sites (1)

Department of Hematology, Nanfang Hospital, Southern Medical University,

Guanzhou, 510515, China

Location

MeSH Terms

Interventions

belimumab

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: professor

Study Record Dates

• First Submitted: October 30, 2022
• First Posted: November 3, 2022
• Study Start: January 1, 2022
• Primary Completion: December 30, 2024
• Study Completion: December 31, 2024
• Last Updated: January 18, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)