A Pilot Study Of Pre-Transplant 5-Azacitidine (Vidaza) In Patients With High-Risk Myelodysplastic Syndrome (MDS) Who Are Candidates For Allogeneic Hematopoietic Cell Transplantation
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 25
- 试验地点
- 1
- 主要终点
- Percentage of Participants With Relapse-free Survival (RFS)
研究概览
简要总结
The purpose of this study is to find out if treating people who have high-risk myelodysplastic syndrome (MDS) with 5-Azacitidine (Vidaza) prior to their allogeneic hematopoietic cell transplant (HCT) is helpful in preventing their myelodysplastic syndrome from coming back.
In previous research, 5-Azacitidine appeared to help the bone marrow of a patient with MDS begin to function more normally. This means bone marrow cells can grow and do their work the way they were meant to. 5-Azacitidine is approved by the Food and Drug Administration (FDA) for the treatment of MDS. The effect of 5-Azacitidine in patients receiving hematopoietic cell transplants have not been studied.
详细描述
RESEARCH PLAN
- This will be a single-center prospective trial
- Patients with high risk MDS that are potentially eligible for HCT will be enrolled.
- A donor search will be initiated, and 5-Azacitidine will be given per standard practice.
- 5-Azacitidine dose is 75 mg/M^2/day subcutaneously by standard practice (generally this is 7 days per monthly cycle, but alterations occur depending on clinical and laboratory parameters).
- Patients where a suitable donor is not found can continue with 5-Azacitidine per standard treatment. These patients will be followed until progression of MDS to acute myelogenous leukemia (AML) or death, for up to one year.
- If a suitable donor is obtained, the patient will proceed to HCT. The HCT conditioning regimen will be dictated by the Blood and Marrow Transplant (BMT) physician. While waiting HCT, additional cycles 5-Azacitidine may be given. Pre-HCT conditioning regimen therapy will begin no more than 8 weeks and no less than 4 weeks after the last administration of 5-Azacitidine.
- As the number of cycles of 5-Azacitidine is not standardized and the retrospective review of our patients noted above indicated a benefit to ANY exposure to 5-Azacitidine, the actual number of cycles of 5-Azacitidine delivered will not be specified. In addition, as high risk MDS patients have an average time to death of 0.4 years, any delay to HCT once it is available is to be avoided.
- A bone marrow biopsy will be performed to reassess disease response to therapy after the last cycle of 5-Azacitidine before transplant, or after the fourth cycle of 5-Azacitidine, whichever comes first. Note that both the biopsy and the timing of the biopsy is a standard evaluation procedure.
- Donor progenitor cell collection will be prescribed by the BMT Attending Physician.
HCT
- The patient will undergo HCT designated per attending BMT physician.
- Supportive care will be based on institutional guidelines, Stem cell collections, processing and laboratory studies
Stem cell collections, processing and laboratory studies
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 68 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Potential candidate for HCT.
- •Histologically confirmed diagnosis by pathologic review of previous diagnosis of high-risk myelodysplastic syndrome (MDS): International Prognostic Scoring System (IPSS) > 1 or AML-MDS or treatment related MDS.
- •Serum bilirubin levels ≤1.5 times the upper limit of the normal (ULN) range for the laboratory. Higher levels are acceptable if these can be attributed to active hemolysis or ineffective erythropoiesis; Serum glutamic-oxaloacetic transaminase (SGOT) [aspartate aminotransferase (AST)] or serum glutamic pyruvic transaminase (SGPT) [alanine aminotransferase (ALT)] levels ≤2 x ULN.
- •Serum creatinine levels ≤1.5 x ULN
- •Karnofsky performance status greater or equal to 70%
- •Signed informed consent form in accordance with institutional policies
排除标准
- •Known or suspected hypersensitivity to Vidaza or mannitol
- •Pregnant or lactating women
- •Human immunodeficiency virus (HIV) or seropositive, confirmed by nucleic acid amplification testing (NAT)
- •Active central nervous system (CNS) malignancy
- •Active infection
- •History or presence of primary hepatoma
研究组 & 干预措施
Combined Therapy
5-azacitidine therapy followed Allogeneic Hematopoietic Cell Transplantation (HCT).
干预措施: 5-azacitidine (Drug)
Combined Therapy
5-azacitidine therapy followed Allogeneic Hematopoietic Cell Transplantation (HCT).
干预措施: Allogeneic Hematopoietic Cell Transplantation (HCT) (Procedure)
结局指标
主要结局
Percentage of Participants With Relapse-free Survival (RFS)
时间窗: One year post allogeneic HCT
Relapse-free survival one year after allogeneic HCT in MDS patients receiving at least one complete cycle of 5-azacitidine (Vidaza) in the pre-transplantation setting. Relapsed disease: if with complete remission (CR) - greater than 5% blasts in bone marrow; if with partial response (PR) - greater than 30% increase in blasts in the marrow; if with stable disease (SD) - return to pretreatment peripheral blood levels and transfusion requirements due to disease.
次要结局
- Percentage of Participants With Overall Survival (OS)(One year)
- Overall Response Rate (ORR)(At the end of up to six (28 day) cycles of 5-azacitidine)
- Percentage of Participants Who Proceed to Hematopoietic Cell Transplantation (HCT)(Up to 3 years)