Phase-II Trial to Assess the Efficacy and Toxicity of 5-Azacitidine in Addition to Standard DLI for the Treatment of Patients With AML or MDS Relapsing After Allogeneic Stem Cell Transplantation
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 30
- 试验地点
- 6
- 主要终点
- Best response
研究概览
简要总结
This open label phase-II trial evaluates hematological response of an additional treatment with 5-Azacitidine to common DLI in patients with MDS or AML relapsing after allogeneic stem cell transplantation.
详细描述
Relapse after allogeneic stem cell transplantation is a major problem in patients with poor prognosis AML or MDS. Donor lymphocyte infusions alone re-induce remission in a minority of these patients, which may be the result of poor differentiation of the leukemic cells. The study drug 5-Aza is effective in AML and MDS.In addition to direct cytotoxicity, it alters gene expression and induces differentiation of leukemic blast cells. Furthermore, DNA-demethylating treatment results in an induction of transcription and cell surface expression of formerly unexpressed KIRs (killer Ig-like receptors) in NK cells, which are involved in the specific recognition of leukemic target cells and who are able to generate a specific graft-versus leukemia effect. The increased expression of MHC class I and II molecules on the surface of the recipient's leukemic cells and the de novo expression of formerly silenced KIR genes in donor NK cells due to treatment with 5-Aza may result in an increased susceptibility of myeloid leukemic cells to the allogeneic graft versus leukemia effect. Therefore, the graft-versus leukemia effect by donor lymphocyte infusions and NK cells from the original donor may be supported by additional therapy with 5-Azacitidine.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- •Primary and secondary MDS, AML after MDS, and de novo AML relapsing after allogeneic stem cell transplantation
- •Eligibility for Donor Lymphocyte Infusions
- •Performance status according to the WHO scale: 0, 1 or
- •Adequate renal and liver function: bilirubin < 1.5 times the upper limit of normal and a GFR > 50 ml/min
- •Absence of severe cardiovascular disease, i.e., arrhythmias requiring chronic treatment, congestive heart failure (NYHA Class III or IV) or symptomatic ischemic heart disease, where New-York Heart Association (NYHA)
- •HIV negative and HBs-Ag negative.
- •Absence of active uncontrolled infection (Septicaemia).
- •No prior history or current evidence of central nervous system and psychiatric disorders requiring hospitalization.
- •Age at least 18 years.
- •Negative pregnancy test for women with reproductive potential.
- •Signed written informed consent must be given according to national/local regulations.
排除标准
- •Have malignant hepatic tumors.
- •Severe liver dysfunction CHILD B and C.
- •Renal insufficiency with a GFR < 50 ml/min
- •Radiation therapy, chemotherapy, or cytotoxic therapy, given to treat conditions other than MDS, AML or applied for conditioning prior allogeneic stemcell transplantation.
- •Psychiatric illness that would prevent granting of informed consent.
- •Treatment with androgenic hormones during the previous 14 days prior Day
- •Active viral infection with known human immunodeficiency virus (HIV) or viral Hepatitis B or C.
- •Hypersensitivity to Mannitol or 5-Azacitidine.
- •Treatment with other investigational drugs following relapse after allogeneic stemcell transplantation or ongoing adverse events from previous treatment with investigational drugs regardless of time period.
研究组 & 干预措施
5-Azacitidine
5-Azacitidine in addition to standard donor lymphocyte infusions.
干预措施: 5-Azacitidine (Drug)
结局指标
主要结局
Best response
时间窗: within the 6 months of treatment
次要结局
- Safety and Toxicity of 5-Azacitidine for patients relapsing after allo-SCT(within 3 years)
- Response rate(within 6 months)
- Duration of remissions(within 3 years)
- Incidence of acute and chronic GvHD(3 years)
- Achievement of complete chimerism(6 month)
- Toxicity(wtihin 3 years)