Single Arm, Open Label, Phase I Study for Dose and Schedule Finding of Decitabine in Patients With Higher-risk MDS and MDS/AML Receiving Allogeneic Stem Cell Transplantation
试验速览
- 阶段
- 1 期
- 入组人数
- 19
- 试验地点
- 1
- 主要终点
- Dose and schedule finding of post-BMT Decitabine Treatment
研究概览
简要总结
Brief Scientific Rationale:
Decitabine has been shown to be effective for treatment of MDS and associated with very limited extramedullary toxicity at the lower doses. Furthermore, the hypomethylating effects of decitabine require an extended period of therapy and are likely to be more beneficial in the setting of a minimal residual disease after transplantation. The drug might exert a cytoreductive effect on the MDS clone, but ex vivo expansion strategy using decitabine and HDAC inhibitor provides a potential to expand the number of hematopoietic stem cells. There are lots of evidence which showed the the drug have immunostimulatory effects and can be used to enhance graft-versus leukemia effects. And also, some investigator suggested that decitabine could induce FOXP3 expression, promoting the conversion of naïve T cells to Tregs which are known to suppress GVHD while maintaining GVL effect in allo-SCT setting. As such, decitabine is an ideal agent to be investigated in the post-transplant setting.
The investigators hypothesized that post-transplant maintenance therapy with decitabine may reduce relapse rate, which may maximize the beneficial effects from reduced TRM of ATG-containing FB4 or FB2 conditioning regimen in higher-risk MDS or AML evolving from MDS patients.
详细描述
- Transplant course
- BMT from an HLA-matched sibling or a suitably matched (up to 2-allele mismatched) family or unrelated donor will be performed according to the policies of the institute.
- A preparative regimen will be started 6 days before the day of stem cell infusion
- Myeloablative-intensity conditioning regimen: FB4+ATG
- Reduced-intensity conditioning regimen; FB2+ATG
- Graft-versus-host disease prophylaxis
- Sibling transplant: Cyclosporine and short-course Methotrexate
- Unrelated transplant: Tacrolimus and short-course Methotrexate
- The dose of calcineurin inhibitors (cyclosporine and tacrolimus) will be gradually tapered from day 60 (for all sibling transplants) or day 90 (for all unrelated transplants) and discontinued within 2 or 3 months after SCT in the absence of graft-versus-host disease.
- Decitabine maintenance course
- For the patients who finish the above transplant procedure and meet the enrollment criteria, decitabine will be given at a dose of 5mg/m2/day ~ 15mg/m2/day iv over 1 hour for 5 consecutive days. The drug will be repeated every 4 weeks for up to 12 cycles.
- Dose escalation strategy between cohorts and between cycles in the same cohort patients will be based upon the quantitatively measured hematological toxicity (e.g., ANC or platelet count at nadir). In other words, a mechanism-based pharmacokinetic / pharmacodynamic model developed using sparsely sampled patients' PK data and toxicity response will be used to titrate next cycle doses for the patients and initial doses for new cohort patients. In other words, a mechanism-based pharmacokinetic / pharmacodynamic model developed using sparsely sampled patients' PK data and toxicity response will be used to titrate next cycle doses for the patients and initial doses for new cohort patients.
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- •HIV positive
- •Active uncontrolled infection
- •Pregnancy or breastfeeding
- •patients who have residual disease after allo SCT or primary graft failure
- •Uncontrolled grade 3- 4 acute GVHD
- •patients who are known or suspected hypersensitivity to decitabine
- •patient who are not suitable for the trial in accordance with principal investigator's decision
研究组 & 干预措施
Decitabine, MDS treatment, IV injection
For the patients who achieve remission after allogeneic BMT and meet the enrollment criteria, decitabine will be given at a dose of 5mg/kg/day ~ 15mg/kg/day iv over 1 hour for 5 consecutive days starting 42-90 days after transplantation. The drug will be repeated every 4 weeks for up to 12 cycles.
干预措施: Decitabine (Drug)
结局指标
主要结局
Dose and schedule finding of post-BMT Decitabine Treatment
时间窗: For up to 2 years after the start of Decitabine
To find the safe dose and schedule of administration of the drug decitabine that can be given to patients with higher risk MDS or secondary AML evolving from MDS who received allogeneic stem cell transplantation
次要结局
- Transplant outcomes of Decitabine maintenance treatment following transplantation(For up to 2 years after the start of Decitabine)
研究者
Yoo-Jin Kim
Associate Professor
Seoul St. Mary's Hospital