NCT03207958已完成1 期
A Pilot Study of Belimumab (Benlysta) for Prevention of Chronic Graft-versus-Host Disease Following Allogeneic Hematopoietic Cell Transplantation
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- 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
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
研究组 & 干预措施
Belimumab
Experimental
- Subjects meeting eligibility criteria will start treatment between Day +30 and Day +80 after alloHCT
- Belimumab will be administered intravenously every 2 weeks for 3 doses followed by 4 doses at monthly intervals, for a total of 7 doses (6 months)
干预措施: Belimumab (Drug)
结局指标
主要结局
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
时间窗: 30 days following the completion of treatment (approximately 7 months)
-Adverse events will be graded according to CTCAE v4.03.
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
时间窗: From start of treatment through 30 days following the completion of treatment (median length of follow-up 205 days, full range 56-229 days)
* 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)
次要结局
- Incidence and severity of acute GvHD(6 months after alloHCT)
- Overall survival(24 months after alloHCT)
- Relapse rate(24 months after alloHCT)
- Overall corticosteroid requirement for treatment of chronic GvHD as measured by duration(24 months after alloHCT)
- Overall corticosteroid requirement for treatment of chronic GvHD as measured by dose(24 months after alloHCT)
- Necessity to use alternative treatment modalities for chronic GvHD(24 months after alloHCT)
- Incidence and severity of chronic GvHD(24 months after alloHCT)
- Overall Corticosteroid Requirement for Treatment of Chronic GvHD(6 months after alloHCT)
- Overall Corticosteroid Requirement for Treatment of Chronic GvHD(12 months after alloHCT)
- Overall Corticosteroid Requirement for Treatment of Chronic GvHD(24 months after alloHCT)
- Incidence and Severity of Chronic GvHD(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(Cycle 3 (each cycle is 4 weeks), Cycle 4, Cycle 5, Cycle 6, Cycle 7, and 6 months)
- Overall Survival(6 months, 12 months, and 24 months after alloHCT)
- Relapse Rate(6 months, 8 months, 12 months, and 24 months post-alloHCT)
- Number of Participants That Required Alternative Treatment Modalities for Chronic GvHD(6 months after alloHCT)
- Number of Participants That Required Alternative Treatment Modalities for Chronic GvHD(12 months after alloHCT)
- Number of Participants That Required Alternative Treatment Modalities for Chronic GvHD(24 months after alloHCT)
研究者
研究点 (1)
Loading locations...
相似试验
撤回
1 期
Belimumab for Treatment of cGVHD Following Allo-HCTcGVHDNCT05604742xuna
已完成
4 期
Efficacy of Basiliximab in the Prevention of Acute Graft-versus-host Disease in Unrelated Allogeneic Hematopoietic Stem Cell Transplantation Therapy for Thalassemia MajorNCT02342145Zhongming Zhang205
终止
不适用
In-Vivo Activated T-Cell Depletion to Prevent GVHDAcute Myelogenous LeukemiaAcute Lymphocytic LeukemiaMyelodysplasiaLymphoma, Non-Hodgkin'sMantle-Cell LymphomaHodgkin's DiseaseMultiple MyelomaChronic Lymphocytic LeukemiaMyelofibrosisChronic Myelogenous LeukemiaNCT00594308Indiana University10
尚未招募
不适用
Bortezomib therapy combined with donor lymphocyte infusion in patients with relapsed Multiple Myeloma following allogeneic stem cell transplantatioMultiple Myeloma/ Multiple Myeloom/ Morbus KahlerAllogeneic stem cell transplantation/allogene stamceltransplantatieDonor lymphocyte infusion/Donor lymfocyten infusieBortezomibNL-OMON25090MC Utrecht, afdeling hematologie20
终止
2 期
Blinatumomab Bridging Therapy for BALLB-cell Acute Lymphoblastic LeukemiaRefractory B Acute Lymphoblastic LeukemiaRelapsed B-cell Acute Lymphoblastic LeukemiaNCT04556084Michael Burke2