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

Completed · Phase 1

Conditions studied: Graft Vs Host Disease, Graft-versus-host-disease

In brief

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 prophylaxis of chronic GvHD. The investigators propose a pilot and feasibility study to assess the safety and tolerability, as well as preliminary efficacy, of belimumab as prophylaxis of chronic GvHD following allogeneic hematopoietic cell transplantation (alloHCT). The investigators' central hypothesis is that belimumab will be well tolerated and have a favorable effect on incidence and severity of chronic GvHD.

Key facts

Study ID: NCT03207958
Run by: Washington University School of Medicine
People needed: 10
Starts: 2018-05-16
Expected to finish: 2024-02-09
Last updated by the study team: 2026-04-20

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

At least 18 years of age
Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
Diagnosis of hematologic malignancy (i.e. acute myeloid leukemia, acute lymphoblastic leukemia, chronic lymphocytic leukemia, chronic myelogenous leukemia, Hodgkin's lymphoma, non-Hodgkin's lymphoma, myelodysplastic syndrome, chronic myelomonocytic leukemia)
Use of myeloablative or non-myeloablative conditioning regimen
Use of mobilized peripheral blood stem cells from fully HLA-matched related or unrelated donor as a graft source
Acute GvHD prophylaxis with methotrexate and tacrolimus
Documented complete remission with full donor engraftment (by STR identity testing) on Day +30 bone marrow biopsy
Complete remission: less than 5% blasts in an aspirate bone marrow sample with a count of at least 200 nucleated cells, no blasts with Auer rods or persistence of extramedullary disease PLUS absolute neutrophil count (ANC) > 1,500/μL, platelet count ≥ 50,000/μL and no leukemic blasts in the peripheral blood.
Negative minimal residual disease
Full donor engraftment by STR testing (either by bone marrow or peripheral blood testing)
Adequate end organ function:
Serum bilirubin ≤ 1.5 x upper limit of normal (ULN)
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x ULN
Creatinine clearance ≥ 40 mL/min/1.73 m\^2 by the Cockcroft-Gault formula
Women of childbearing potential must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry, for the duration of study participation, and for 16 weeks after the last dose of study drug. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
Able to understand and willing to sign an Institutional Review Board (IRB)-approved written informed consent.

You may not qualify if…

Active grade III-IV classic acute GvHD; subjects with prior resolved acute GvHD on stable doses of immunosuppression at time of enrollment will be permitted
Evidence of classic chronic GvHD or overlap chronic GvHD at time of enrollment
Subjects who participated in a clinical trial of acute GvHD prophylaxis in which chronic GvHD was a secondary end point
Donor lymphocyte infusion administered to treat relapse or loss of donor chimerism
Treatment with rituximab or other anti-B cell specific antibodies within previous 3 months
History of other malignancy ≤ 5 years previous with the exception of basal cell or squamous cell carcinoma of the skin which were treated with local resection only or carcinoma in situ of the cervix
Currently receiving any other investigational agents
Known allergy or intolerance to any component of belimumab, including human or murine proteins or monoclonal antibodies
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations (including current drug or alcohol abuse or dependence, or history of drug or alcohol abuse or dependence within the last year) that would limit compliance with study requirements
Use of parenteral (IV or IM) antibiotics (antibacterials, antivirals, anti-fungals, or anti-parasitic agents) within 14 days prior to planned start of therapy
Evidence of serious suicide risk including any history of suicidal behavior in the last 6 months and/or any suicidal ideation in the last 2 months and/or poses a significant suicide risk in the judgment of the investigator
History of pre-existing immunodeficiency disorder, autoimmune condition, or chronic infection
Known HIV positivity
Serologic evidence of current or past hepatitis B infection based on the results of testing for HBsAg and anti-HBc - Patients positive for HBsAg or HBcAb are excluded
Positive test for hepatitis C antibody (patients with documented clearance of hepatitis C by PCR following treatment will be permitted)
Currently on therapy for active chronic infection (such as tuberculosis, pneumocystis, cytomegalovirus, herpes simplex virus, herpes zoster and atypical mycobacteria). Prophylactic therapy is allowed.
Has any other clinically significant abnormal laboratory value in the opinion of the investigator

Where it is running

Washington University School of Medicine — St Louis, Missouri, United States

Full record on ClinicalTrials.gov

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