A Randomized Phase II Trial Comparing a Calcineurin Inhibitor-free Graft-versus-host Disease Prophylaxis Regimen With Post-transplantation Cyclophosphamide and Abatacept to Standard of Care
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 43
- 试验地点
- 1
- 主要终点
- Occurrence of Moderate and Severe Chronic GVHD at One Year Post Transplant
研究概览
简要总结
The purpose of this study is to investigate whether the combination of cyclophosphamide and abatacept versus the treatment used in standard of care will reduce the incidence of moderate and severe chronic graft-versus-host disease (GVHD) following hematopoietic stem cell transplantation. GVHD occurs when the cells from your donor (the graft) see your body's cells (the host) as different and attack them.
详细描述
The experimental GVHD prophylaxis arm consists of cyclophosphamide and abatacept. Cyclophosphamide induces apoptosis of activated T cells and abatacept (CTLA4Ig) blocks activation of T cells by inhibiting the co-stimulatory signal.
Compared to the standard-of-care control arm, the experimental arm is much more convenient and expected to be associated with fewer toxicities.
In addition there is a great theoretical potential for immunological synergy between cyclophosphamide and abatacept for inducing post-transplant immunologic tolerance that clinically might translate into less GVHD without increase in relapse Patients will be randomized 1:1 to the experimental vs the standard of care arm. Randomization will be done prior to the use of any conditional therapy.
The two arms will be stratified by disease (acute leukemia vs others) and donor type (MRD vs MUD/MUD vs Haplo) in an effort to keep them balanced.
The conditioning regimen for both arms will be mainly Busulfan/Fludarabine (A Total Body Irradiation based conditioning regimen will be allowed for diseases such as ALL)
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •High risk hematologic malignancy justifying the need for an allogeneic hematopoetic stem cell transplantation: AML, ALL, CML in accelerated or blast phase, MDS/MPN, NHL, Hodgkin lymphoma, and multiple myeloma
- •Creatinine clearance > 40
- •Adequate hepatic function
- •Normal cardiac function (EF > 50%)
排除标准
- •Patients with hematologic malignancies for which transplant is not the only curative option, such as AML with good or intermediate cytogenetics or molecular markers in CR1 or CML in chronic phase
- •Inability to identify an 10/10 HLA-Matched Donor (related or unrelated) or a haploidentical donor
- •Active malignant disease relapse
- •Active, uncontrolled infection, uncontrolled cardiac angina, symptomatic congestive heart failure
- •Life expectancy <3 months
- •Pregnancy or lactation
- •Patients may not be receiving any other investigational agents in the last 28 days
- •Patients with chronic myeloid leukemia in first chronic phase
研究组 & 干预措施
Cyclophosphamide and abatacept
The GVHD prophylaxis regimen on the experimental arm will consist of high dose Cyclophosphamide on Days +3 and +4 followed by abatacept for 6 months. Abatacept at a dose of 10mg/kg will be administered on days +5, +14 and +28, +56, +84, +112, +140, +168
干预措施: Cyclophosphamide (Drug)
Cyclophosphamide and abatacept
The GVHD prophylaxis regimen on the experimental arm will consist of high dose Cyclophosphamide on Days +3 and +4 followed by abatacept for 6 months. Abatacept at a dose of 10mg/kg will be administered on days +5, +14 and +28, +56, +84, +112, +140, +168
干预措施: abatacept (Drug)
methotrexate and tacrolimus
The GVHD prophylaxis regimen on the standard of care arm will consist of methotrexate on Days +1,+3, +6 and +11 and tacrolimus
干预措施: Methotrexate (Drug)
methotrexate and tacrolimus
The GVHD prophylaxis regimen on the standard of care arm will consist of methotrexate on Days +1,+3, +6 and +11 and tacrolimus
干预措施: Tacrolimus (Drug)
结局指标
主要结局
Occurrence of Moderate and Severe Chronic GVHD at One Year Post Transplant
时间窗: through study completion, an average of 1 year
The occurrence of moderate and severe chronic GVHD at one year post Chronic GVHD will be diagnosed and staged according to the previously published and widely accepted National Institutes of Health consensus criteria
次要结局
- GVHD- and Relapse- Free Survival by One Year Post Transplant(through study completion, an average of 1 year)
研究者
Dimitrios Tzachanis, MD PhD
Assistant Clinical Professor of Medicine
University of California, San Diego