Bortezomib-based Graft-Versus-Host-Disease Prophylaxis After Myeloablative Allogeneic Stem Cell Transplantation for Patients Lacking HLA-matched Related Donors: A Phase 2 Study
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 35
- 试验地点
- 1
- 主要终点
- The Cumulative Incidence of Grade II-IV Acute GVHD up to Day 100 After Stem Cell Infusion
研究概览
简要总结
A common problem after stem cell transplant is graft-versus-host-disease (GVHD). GVHD is a complication of transplantation where the donor graft attacks and damages some of your tissues. After stem cell transplant, all patients receive prophylactic medications against GVHD.
In this research study, we are studying the safety and effectiveness of a bortezomib based GVHD prophylaxic drug combination in participants after myeloablative allogeneic stem call transplantation from a matched unrelated donor, mismatched related or unrelated donor.
详细描述
Before your transplant you will receive conditioning therapy with fludarabine and busulfan given 7, 6, 5, and 4 days before your transplant. On day 0, you will receive selected blood cells taken from your sibling or unrelated donor.
You will receive 3 drugs for your GVHD prophylaxis:
Tacrolimus will be started 3 days before your transplant. It will be given intravenously and later by mouth. You will continue to take tacrolimus for 3 to 6 months after transplant.
Methotrexate will be given intravenously 1, 3, 6 and 11 days after your transplant.
Bortezomib will be given intravenously 1, 4, and 7 days after your transplant. On days 1, 4, 7, 30 and 3, 6 and 12 months after your transplant you will have a physical exam, blood work, and be asked to complete a questionnaire.
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 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically or cytologically confirmed advanced and/or aggressive hematologic malignancy (including myelodysplastic syndrome) that is unlikely to be cured by alternative therapies
- •HLA-Matched unrelated donor; or 1-locus HLA-mismatched related or unrelated donor
- •ECOG performance status 0-2
- •Adequate organ function
- •Able to understand and willing to sign a written informed consent document
- •Agrees to practice adequate contraception per study requirements
排除标准
- •Pregnant or breastfeeding
- •Recipient of prior allogeneic or autologous stem cell transplantation
- •Prior abdominal radiation therapy
- •HIV-positive on combination antiretroviral therapy
- •Seropositive for hepatitis B or C
- •Allergies to bortezomib, boron, or mannitol
- •Myocardial infarction within last 6 months, NYHA Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias
- •Uncontrolled bacterial, viral or fungal infections
- •Seizures or history of seizures
- •History of another non-hematologic malignancy unless disease-free for at least 5 years
- •Uncontrolled intercurrent illness
研究组 & 干预措施
Velcade/Tac/MTX
Drug: Bortezomib. Other Names: Velcade. Bortezomib 1.3 mg/m^2 IV
Drug: Tacrolimus. Tacrolimus 0.05 mg/kg PO bid
Drug: Methotrexate. Methotrexate 15 mg/m^2 IV
干预措施: Methotrexate (Drug)
Velcade/Tac/MTX
Drug: Bortezomib. Other Names: Velcade. Bortezomib 1.3 mg/m^2 IV
Drug: Tacrolimus. Tacrolimus 0.05 mg/kg PO bid
Drug: Methotrexate. Methotrexate 15 mg/m^2 IV
干预措施: Bortezomib (Drug)
Velcade/Tac/MTX
Drug: Bortezomib. Other Names: Velcade. Bortezomib 1.3 mg/m^2 IV
Drug: Tacrolimus. Tacrolimus 0.05 mg/kg PO bid
Drug: Methotrexate. Methotrexate 15 mg/m^2 IV
干预措施: Tacrolimus (Drug)
结局指标
主要结局
The Cumulative Incidence of Grade II-IV Acute GVHD up to Day 100 After Stem Cell Infusion
时间窗: Day 100
The primary outcome of this study is the cumulative incidence of grade II-IV acute GVHD up to Day 100 after stem cell infusion. Acute GHVD is graded according to the modified Glucksberg criteria (adapted from Thomas et al., NEJM ,1975, pp. 895-90), which is based on criteria by which the provider classifies acute GVHD per its objective organ staging. Acute GVHD is assessed in weekly standard of care visits post stem cell infusion and is captured in the protocol EDC upon evaluation of clinical notes up to Day 100. Data for acute GVHD organ staging and etiologies are collected in an acute GVHD separate case report form and do not include system organ class, expectedness or attribution.
次要结局
- The Cumulative Incidence of Chronic GVHD Requiring Systemic Immune Suppression up to 1 Year After Stem Cell Infusion(1 year)
- The Non-relapse Mortality, Progression-free and Overall Survival up to 1 Year After Stem Cell Infusion(1 year)
- The Percentage Donor Engraftment up to Day 30 Post Stem Cell Infusion(Day 30)
研究者
John Koreth, MD
Principal Investigator
Dana-Farber Cancer Institute