Study of Fludarabine Based Conditioning for Allogeneic Stem Cell Transplantation for Myelofibrosis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 66
- 试验地点
- 12
- 主要终点
- The Primary Endpoint is Progression-free Survival.
研究概览
简要总结
Stem cell transplantation is used to treat may types of diseases. There a 2 types of transplants, conventional (very intense) and reduced intensity-non-myeloablative, also called mini-transplants.
This study proposes to use a conditioning regimen for allogeneic transplantation along with a reduced intensity transplant. Conditioning regiment is the name for the combination of chemotherapy drugs that is given to patients before receiving a transplantation of donor stem cells. It is hoped that the regimen designed for this study proves to be less toxic and has an equal or better anticancer effect than the regimens that are normally used. The regimen being used is a combination of two chemotherapy drugs, fludarabine and melphalan. This regimen has been studied in recipients of matched sibling transplants and in recipients of alternative donor stem cells in other hematologic malignancies. Those subjects, who receive stem cells from an unrelated donor, will also receive and additional drug called ATG or anti thymocyte globulin. ATG suppresses the immune system, thus reducing the chances for the recipient rejecting the transplant (graft).
The purpose of this study is to observe if reduced intensity transplants can be used to allow engraftment or "take" of the donor's bone marrow. Studies conducted in the past show this type of transplant is much less toxic than traditional bone marrow transplants. Reduced intensity transplants may be better tolerated by patients who may experience serious side effects from standard (very intense) stem cell transplant.
The study has been recently amended to follow all subjects for survival.
详细描述
This study is designed as a single arm Phase II clinical trial in patients with myelofibrosis who are eligible for transplantation from a related donor or from an unrelated donor source. Patients will be accrued into two separate strata defined by donor type. Each of the two strata will be analyzed separately.
Patients will be followed yearly from time of enrollment into the study to assess clinical response and overall, progression and event free survival, as well as incidence and degree of acute and chronic GVHD. We will estimate cumulative survival and transplant related mortality in patients enrolled in each of the two strata.
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
- •Patients with the following disease: Idiopathic myelofibrosis, or spent PV-, or ET-related myelofibrosis in chronic phase (<20% blast cells in the bone marrow) with Lille score >1 at any time, or platelet <100K.
- •Age 18-65 years.
- •ECOG performance status <
- •Life expectancy >3 months.
- •Adequate cardiac function, normal LVEF ≥ 45% by MUGA or echocardiogram and adequate pulmonary function DLCO ≥ 50% of predicted.
- •Serum creatinine < 1.1 x the upper limit of normal (ULN) or Creatinine Clearance >50 ml/min.
- •Serum bilirubin < 2.0 mg/dl, SGPT <2.5 x upper limit of normal
- •No evidence of chronic active hepatitis or cirrhosis
- •HIV-negative
- •Patient is not pregnant
- •Patient or guardian able to sign informed consent.
- •Patients with >20% myeloblasts in the blood or marrow, extramedullary blast cell proliferation or large foci of blasts in bone marrow biopsy specimens are not eligible.
- •Pretransplant splenectomy: MMM patients with variable degrees of splenomegaly, or splenectomized, are eligible to be enrolled. Any decision of having a patient splenectomized prior to transplant will be made in each center prior to enrolling the patient in the study.
- •Patients should be off treatment with investigational for at least 4 weeks and have recovered from all toxicities.
排除标准
- •Pregnancy
- •HIV positive
- •> 20% myeloblasts in the peripheral blood or bone marrow
- •LVEF < 45%
- •DLCO < 50% of predicted
- •ECOG performance status ≥ 3
- •Chronic active hepatitis or cirrhosis
- •Chronic renal insufficiency
研究组 & 干预措施
Fludarabine, Melphalan +/- ATG
Fludarabine, Melphalan +/- ATG
干预措施: Fludarabine, Melphalan +/- ATG (Drug)
结局指标
主要结局
The Primary Endpoint is Progression-free Survival.
时间窗: 2 years
Number of participants alive at 2 years who are progression-free
次要结局
- Response Outcomes(180 days)
- Overall Survival(73 months)
- PLT(2 years)
- Absolute Neutrophil Count (ANC)(2 years)
- Transplant-related Mortality(2 years)
研究者
John Mascarenhas
Assistant Professor
Icahn School of Medicine at Mount Sinai