Natural Killer Cel Alloreactive Bone Marrow Transplantation for Multiple Myeloma
试验速览
- 阶段
- 1 期
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Progression free survival (scale)
研究概览
简要总结
The aim of this phase 2 study is to demonstrate that KIR-ligand mismatched haploBMT with post-transplant cyclophosphamide will improve progression free survival in poor risk multiple myeloma patients.
详细描述
The goal of this study is to evaluate the effectiveness of a new treatment modality, the KIR-ligand mismatched haploidentical stem cell transplantation (haploBMT), for poor risk multiple myeloma (MM) patients. MM is a malignancy of plasma cells that usually resides in the bone marrow. Despite new treatment modalities that have been introduced in the last years, MM is still an incurable disease for most patients and median survival for the younger patients (<65) is about 5 years. MM can be treated by several disease modifiers - classical chemotherapy, high dose chemotherapy and autologous stem cell transplantation (ASCT), immunomodulators like thalidomide and lenalidomide, and drugs like bortezomib that interact with relevant intracellular pathways of malignant plasma cells. Though these treatment modalities have improved overall survival and quality of life, patients are not cured.
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
- •Patients with MM <60 years.
- •Poor prognosis MM patients, permissive for KIR-ligand mismatch and with a KIR-ligand mismatched haploidentical donor. Poor prognosis is based on:
- •Patients with early disease recurrence (within 12 months after first ASCT) or
- •Patients after a minimum of three lines of chemotherapy (including high dose therapy followed by ASCT rescue therapy) or
- •Poor risk based on the cytogenetic profile.
- •Written informed consent
- •No HLA identical related or 10/10 matched unrelated donor
- •Permissive for KIR-ligand mismatch
- •Responsive after reinduction therapy
- •Measurable disease
排除标准
- •- Patients with an full matched (10/10) donor, who will enroll in the HOVON 96 study
- •Active uncontrolled infections
- •Uncontrolled CNS involvement by the malignant disease
- •Severe cardiovascular disease (arrhythmias requiring chronic treatment, congestive heart failure or symptomatic ischemic heart disease)
- •Severe pulmonary dysfunction (CTCAE grade III-IV)
- •Severe neurological or psychiatric disease
- •Significant hepatic dysfunction (serum bilirubin or transaminases ≥ 3 times upper limit of normal)
- •Significant renal dysfunction (creatinine clearance < 30 ml/min after rehydration)
- •History of active malignancy during the past 5 years with the exception of basal carcinoma of the skin or stage 0 cervical carcinoma
- •Any psychological, familial, lingual, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule
- •Breast-feeding female patients.
- •Concurrent severe and/or uncontrolled medical condition (DM, hypertension, cancer).
研究组 & 干预措施
Bone MarrowTransplantation
KIR-mismatched haploidentical bone marrow transplantation
干预措施: Donor Bone Marrow stem cell transplantation (Procedure)
结局指标
主要结局
Progression free survival (scale)
时间窗: 1 year
次要结局
- Response rate (scale)(analyzed at -7, 30, 60, 90, 120, 150, 180, 270 and 360 days post-transplatation)
- Incidence of graft failure, engraftment and time to neutrophil and platelet recovery (hematology)(30 days after transplantation)
- Incidence and Severity of Acute and Chronic GVHD (scale)(analyzed during follow-up of 1,5 years)
- Non-Relapse Mortality (number)(1.5 years)
- Evaluation of infections after haploBMT and T cell reconstitution (scale)(1 year after transplantation)
- NK cell repertoire reconstitution and maturation rates including alloreactivity (facs)(1 year after transplantation)
- NK cell repertoire in the Bone Marrow before and after transplantation (facs)(6 weeks after transplantation)
- Cost calculation (euro)(1.5 years)
- Quality of Life (questionnaire)(1.5 years)
研究者
Gerard Bos
Prof Dr
Maastricht University Medical Center