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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
10
-Given over 1 hour
Washington University School of Medicine
St Louis, Missouri, United States
Safety and Tolerability of Belimumab as Prophylaxis of Chronic GvHD in Subjects Following alloHCT as Measured by Number of Participants Who Experience Each Adverse Event
* Adverse events were graded according to CTCAE v4.03. * All adverse events were collected with the exception of: * Adverse events that are less than CTCAE grade 3 unless the AE met the definition of a serious adverse event. * Adverse events not of special interest as defined in the protocol (special interest AEs will be recorded regardless of grade, including those thought to be related to chronic GvHD)
Time frame: From start of treatment through 30 days following the completion of treatment (median length of follow-up 205 days, full range 56-229 days)
Incidence and Severity of Chronic GvHD
-The presence of chronic GvHD will be determined according to the 2014 NIH Criteria. If chronic GvHD is diagnosed, each organ will be scored 0-3 and graded, according to the 2014 NIH criteria for Diagnosing and Staging of Chronic GvHD. These data will allow calculation of the NIH global severity score of mild, moderate or severe.
Time frame: Cycle 3 (each cycle is 4 weeks), Cycle 4, Cycle 5, Cycle 6, Cycle 7, 6 months, 9 months, 12 months, 15 months, 18 months, 21 months, and 24 months
Incidence and Severity of Acute GvHD
* Acute GvHD staging has 4 organ systems: skin, lower gastrointestinal (GI), upper GI, and liver. * Skin (% body surface area): stage 0 no rash, stage 1 \< 25%, stage 2 25%-50%, stage 3 \>50%, stage 4 generalized erythroderma with bullae * Lower GI (diarrhea, mL/day): stage 0 \<500, stage 1 \>500, stage 2 \>1000, stage 3 \>1500, stage 4 severe abdominal pain +/- ileus * Upper GI: only stage is stage 1 which is persistent, severe nausea * Liver (bilirubin, mg/dL): stage 0 ≥2, stage 1 2.1-3, stage 2 3.1-6, stage 3 6.1-15, stage 4 \>15 * Acute GvHD will be graded according to modified Minnesota grading scale. Organ systems are broken down into skin, liver, lower gastrointestinal (GI), and upper gastrointestinal (GI) and the grades are I, II, III, IV. * I: skin stage 1-2, liver/lower GI/upper GI stage 0 * II: skin stage 3, liver/lower GI/upper GI stage 1 * III: liver stage 2-4, lower GI stage 2-3 * IV: skin stage 4, lowr GI stage 4 Grade IV is t
Time frame: Cycle 3 (each cycle is 4 weeks), Cycle 4, Cycle 5, Cycle 6, Cycle 7, and 6 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.
Time frame: 6 months, 12 months, and 24 months after alloHCT
Relapse Rate
Time frame: 6 months, 8 months, 12 months, and 24 months post-alloHCT
Overall Corticosteroid Requirement for Treatment of Chronic GvHD
Time frame: 6 months after alloHCT
Overall Corticosteroid Requirement for Treatment of Chronic GvHD
Time frame: 12 months after alloHCT
Overall Corticosteroid Requirement for Treatment of Chronic GvHD
Time frame: 24 months after alloHCT
Number of Participants That Required Alternative Treatment Modalities for Chronic GvHD
-The use of additional systemic immune suppressive agents will be captured at each study visit.
Time frame: 6 months after alloHCT
Number of Participants That Required Alternative Treatment Modalities for Chronic GvHD
-The use of additional systemic immune suppressive agents will be captured at each study visit.
Time frame: 12 months after alloHCT
Number of Participants That Required Alternative Treatment Modalities for Chronic GvHD
-The use of additional systemic immune suppressive agents will be captured at each study visit.
Time frame: 24 months after alloHCT
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