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

Conditions:Orthopedic, Hematology
Therapuetic Areas:Hematology, Orthopedics / Podiatry
Age Range:18 - Any
Start Date:May 16, 2018
End Date:April 16, 2021
Contact:Iskra Pusic, M.D.

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A Pilot Study of Belimumab (Benlysta) for Prevention 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 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.

Inclusion Criteria:

- 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) in complete remission at the time of transplant

- Use of 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

- 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.

Exclusion Criteria:

- 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

- 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

- 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
We found this trial at
660 S Euclid Ave
Saint Louis, Missouri 63110
(314) 362-5000
Principal Investigator: Iskra Pusic, M.D.
Phone: 314-454-8304
Washington University School of Medicine Washington University Physicians is the clinical practice of the School...
Saint Louis, MO
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