Clinical trial NCT05604742: Belimumab for Treatment of cGVHD Following Allo-HCT
Official title: Belimumab for Treatment of Chronic Graft-versus-Host Disease Following Allogeneic Hematopoietic Cell Transplantation
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
PHASE2
Conditions: cGVHD
Keywords: cGVHD
Resistance
belimumab
Lead sponsor: Nanfang Hospital, Southern Medical University
Sponsor class: OTHER
First posted: 2022-11-03
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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 -

Primary outcomes:
measure: Overall response rate of chronic GvHD after belimumab treatment
timeFrame: approximately 6 months
Secondary outcomes:
measure: Duration of response rate of chronic GvHD after belimumab treatment
timeFrame: 12 months
Other outcomes:
measure: Safety and tolerability of belimumab as treatment of chronic GvHD
timeFrame: approximately 12 months
measure: Overall survival
timeFrame: 24 months
Locations:
city: Guanzhou
country: China
facility: Department of Hematology, Nanfang Hospital, Southern Medical University,
Study officials:
References: