A Multi-Center Biologic Assignment Trial Comparing Allogeneic Hematopoietic Cell Transplant to Hypomethylating Therapy or Best Supportive Care in Patients w/Intermediate-2 & High Risk Myelodysplastic Syndrome (BMTCTN1102)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 384
- 试验地点
- 72
- 主要终点
- Percentage of Participants With Overall Survival (OS)
研究概览
简要总结
This study is designed as a multicenter trial, with biological assignment to one of two study arms; Arm 1: Reduced intensity conditioning allogeneic hematopoietic cell transplantation (RIC-alloHCT), Arm 2: Non-Transplant Therapy/Best Supportive Care.
详细描述
Background: MDS is a clonal disorder of hematopoietic precursors and stem cells, which may evolve to a terminal phase resembling acute leukemia. A subject of clinical urgency for researchers, clinicians, patients, and health care underwriters such as Medicare, is the role of allogeneic hematopoietic cell transplantation (alloHCT) in the treatment of older patients with higher risk myelodysplastic syndromes (MDS). The use of reduced intensity conditioning (RIC) regimens has extended HCT to the care of older patients with acute myelogenous leukemia (AML) and lymphoma and a number of retrospective and phase II trials for patients with MDS now show the curative potential of RIC alloHCT in selected patients.
This protocol is designed to evaluate the relative benefits of RIC alloHCT compared to non-transplant therapies focusing on overall survival. This will be done by having patients biologically assigned to the alloHCT arm or the hypomethylating therapy/best supportive care arm and following them for survival at 3 years.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
盲法说明
No parties are masked in this trial.
入排标准
- 年龄范围
- 50 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients fulfilling the following criteria will be eligible for entry into this study:
- •Patients with de novo MDS who have, or have previously had, Intermediate-2 or High risk disease as determined by the International Prognostic Scoring System (IPSS). Current Intermediate-2 or High risk disease is NOT a requirement.
- •Patients must have an acceptable MDS subtype:
- •Refractory cytopenia with unilineage dysplasia (RCUD) (includes refractory anemia (RA))
- •Refractory anemia with ringed sideroblasts (RARS)
- •Refractory anemia with excess blasts (RAEB-1)
- •Refractory anemia with excess blasts (RAEB-2)
- •Refractory cytopenia with multilineage dysplasia (RCMD)
- •Myelodysplastic syndrome with isolated del(5q) (5q-syndrome)
- •Myelodysplastic syndrome (MDS), unclassifiable
- •Patients must have fewer than 20% marrow blasts within 60 days of consent.
- •Patients may have received prior therapy for the treatment of MDS, including but not limited to: growth factor, transfusion support, immunomodulatory (IMID) therapy, DNA hypomethylating therapy, or cytotoxic chemotherapy prior to enrollment.
- •Age 50.0-75.0 years.
- •Karnofsky performance status > 70 or Eastern Cooperative Oncology Group (ECOG) ≤
- •Patients are eligible if no formal unrelated donor search has been activated prior to date of consent. A formal unrelated donor search begins at the time at which samples are requested from potential National Marrow Donor Program (NMDP) donors. Patients who have started a sibling donor search or who have found a matched sibling donor are eligible.
- •Patients and physicians must be willing to comply with treatment assignment:
- •No intent to proceed with alloHCT using donor sources not specified in this protocol, including human leukocyte antigen (HLA)-mismatched related or unrelated donors (< 6/6 HLA related matched or < 8/8 HLA unrelated matched) or umbilical cord blood unit(s).
- •No intent to use myeloablative conditioning regimens.
- •Intent to proceed with RIC alloHCT if a matched sibling or matched unrelated donor is identified. There is no requirement as to the timing of the transplantation.
- •Patients must be considered to be suitable RIC alloHCT candidates at the time of enrollment based on medical history, physical examination, and available laboratory tests. Specific testing for organ function is not required for eligibility but, if available, these tests should be used to judge eligibility.
- •Signed informed consent
排除标准
- •Patients with the following will be ineligible for registration onto this study:
- •Therapy-related MDS (defined as the occurrence of MDS due to prior exposure to systemic chemotherapy and/or radiation for malignancy)
- •Current or prior diagnosis of AML
- •Chronic myelomonocytic leukemia or myelodysplastic/myeloproliferative neoplasm (unacceptable MDS subtypes); uncontrolled bacterial, viral or fungal infection (currently taking medication and with progression or no clinical improvement) at time of enrollment.
- •Patients with prior malignancies, except treated non-melanoma skin cancer or treated cervical carcinoma in situ. Cancer treated with curative surgery without chemotherapy/radiation therapy > 5 years previously will be allowed. Cancer treated with curative surgery < 5 years previously will not be allowed unless approved by the Protocol Officer or one of the Protocol Chairs.
- •Prior autologous or allogeneic HCT
- •Human Immunodeficiency Virus (HIV) infection
- •Patients of childbearing potential unwilling to use contraceptive techniques
- •Patients with psychosocial conditions that would prevent study compliance
结局指标
主要结局
Percentage of Participants With Overall Survival (OS)
时间窗: 3 years
The primary endpoint for this study is overall survival (OS) at three years post-consent. Death from any cause will be considered an event for this endpoint. Surviving participants are censored at the time of last follow-up. Three year OS estimates are adjusted for age, race/ethnicity, performance status, IPSS score, duration of disease, and response to prior hypomethylating therapy. The results posted are from the February 2020 interim analysis per protocol study design. Two interim analyses for efficacy were performed previously in January and November 2019 and presented to the Data and Safety Monitoring Board (DSMB). Results at the second analysis was crossing the efficacy boundary. Subsequently, the DSMB approved early release of study data as of February 2020.
次要结局
- Percentage of Participants With Leukemia-free Survival (LFS)(3 years)
- Quality of Life (QOL) - Medical Outcomes Study Short Form (MOS SF-36)(3 years)
- Percentage of Participants on HCT Arm With Overall Survival (OS)(27 months post-transplant)
- Quality of Life (QOL) - Functional Assessment of Cancer Therapy-General (FACT-G)(3 years)
- Quality of Life (QOL) - EQ-5D(3 years)
- Percentage of Participants With Overall Survival (OS) in As-treated Population(3 years)
- Percentage of Participants on HCT Arm With Disease Relapse(27 months post-transplant)
- Percentage of Participants on HCT Arm With Grade II-IV Acute GVHD (aGVHD)(27 months post-transplant)
- Percentage of Participants With Leukemia-free Survival (LFS) in As-treated Population(3 years)
- Percentage of Participants on HCT Arm With Chronic GVHD(27 months post-transplant)
- Percentage of Participants on HCT Arm With Disease-free Survival (DFS)(27 months post-transplant)
- Percentage of Participants on HCT Arm With Treatment-related Mortality(27 months post-transplant)
- Percentage of Participants on HCT Arm With Grade III-IV Acute GVHD(27 months post-transplant)