Belimumab for Treatment of cGVHD Following Allo-HCT

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

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.

Study Overview

• Status: Withdrawn
• Conditions: cGVHD
• Intervention / Treatment: Drug: Belimumab (Benlysta)

• Study Type: Interventional
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Guanzhou, China, 510515
    • Department of Hematology, Nanfang Hospital, Southern Medical University,

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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:

1. Relapsed or progressive malignant disease (other than minimal residual disease)
2. History of other malignant diseases, including post-transplant lymphoproliferative disease
3. Rituximab or other anti-B cell-specific antibodies were used in the past 3 months.
4. Uncontrolled infections (including prior aspergillosis) not responsive to antibiotics, antiviral medicines, or antifungal medicines
5. Donor lymphocyte transfusion for donor chimeric relapse or loss.
6. 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 -

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and tolerability of belimumab as treatment of chronic GvHD	Adverse events will be graded according to CTCAE v4.03.	approximately 12 months
Overall survival	Overall survival will be determined from date of belimumab initiation, with death from any cause as the event of interest, and censoring at last follow up date for those with incomplete observations. Overall survival will be determined from date of belimumab initiation, with death from any cause as the event of interest, and censoring at last follow up date for those with incomplete observations. Overall survival will be determined from date of belimumab initiation, with death from any cause as the event of interest, and censoring at last follow up date for those with incomplete observations.	24 months

Collaborators and Investigators

• Sponsor: xuna

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2022
• Primary Completion (Anticipated): December 30, 2024
• Study Completion (Anticipated): December 31, 2024

Study Registration Dates

• First Submitted: October 30, 2022
• First Submitted That Met QC Criteria: October 30, 2022
• First Posted (Actual): November 3, 2022

Study Record Updates

• Last Update Posted (Actual): January 18, 2023
• Last Update Submitted That Met QC Criteria: January 16, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: Resistance; cGVHD; belimumab
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Immunosuppressive Agents; Immunologic Factors; Belimumab
• Other Study ID Numbers: cGVHD202210310

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No