Belimumab for Treatment of cGVHD Following Allo-HCT

Study Overview
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Brief Summary
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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.

Official Title
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Belimumab for Treatment of Chronic Graft-versus-Host Disease Following Allogeneic Hematopoietic Cell Transplantation

Conditions
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cGVHD

Intervention / Treatment
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* Drug: Belimumab (Benlysta)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1.18 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). 7.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. 8.Patients tested positive for autoantibodies (ANA titer ≥1:80) and high BAFF levels (plasma concentration ≥15ng/ml). 9.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 Exclusion Criteria: 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 -

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low-dose group of Belimumab<br>Belimumab 1mg/kg com combined with conventional therapy | Drug: Belimumab (Benlysta)<br>* Belimumab will be administered intravenously every 2 weeks for 3 cycles and then every 4 weeks for a total of 5 cycles<br>|
| Experimental: High-dose group of Belimumab<br>Belimumab 4mg/kg com combined with conventional therapy | Drug: Belimumab (Benlysta)<br>* Belimumab will be administered intravenously every 2 weeks for 3 cycles and then every 4 weeks for a total of 5 cycles<br>|
| No Intervention: Control group<br>conventional therapy | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate of chronic GvHD after belimumab treatment | cGVHD grade according NIH | approximately 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of response rate of chronic GvHD after belimumab treatment | Duration of ORR chronic GvHD after belimumab treatment | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cGVHD, Resistance, belimumab