Pilot Safety and Feasibility Trial of Mycophenolate and Sirolimus for Prevention of GVHD in Mismatched Unrelated and Related Donor Hematopoietic Stem Cell Transplantation for Hematologic Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 1
- 试验地点
- 1
- 主要终点
- Incidence of acute GvHD grade 3 & 4, according to the Glucksberg staging criteria
研究概览
简要总结
This pilot phase I/II trial studies the side effects and how well sirolimus and mycophenolate mofetil work in preventing graft versus host disease (GvHD) in patients with hematologic malignancies undergoing hematopoietic stem cell transplant (HSCT). Biological therapies, such as sirolimus and mycophenolate mofetil, use substances made from living organisms that may stimulate or suppress the immune system in different ways and stop tumor cells from growing. Giving sirolimus and mycophenolate mofetil after hematopoietic stem cell transplant may be better in preventing graft-versus-host disease.
详细描述
PRIMARY OBJECTIVES:
I. Evaluate the safety and feasibility of administering sirolimus and mycophenolate mofetil (MMF) as prophylaxis of grade III-IV acute graft versus host disease (aGvHD) in patients undergoing mismatched unrelated and related donor hematopoietic stem cell transplant (HSCT).
OUTLINE:
Patients receive sirolimus orally (PO) starting on day -3, 3 times a week during hospitalization and then once a week for up to 6 months. Patients undergo HSCT on day 0. Patients also receive mycophenolate mofetil intravenously (IV) or PO three times a day (TID) on days 1-180. Treatment continues in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at days 30, 60, 100, 180, 270, and 365, and then yearly thereafter.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 3 Years 至 30 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects must have one of the following disease categories:
- •Acute myeloid leukemia (AML) beyond 2nd remission or relapsed/refractory disease
- •Acute lymphoblastic leukemia (ALL) beyond 2nd remission or relapsed/refractory disease
- •Chronic myeloid leukemia (CML) beyond 2nd chronic phase or in blast crises
- •Myelodysplastic syndrome (MDS)
- •Myeloproliferative disorders including myeloid metaplasia and myelofibrosis
- •High risk non-Hodgkin's lymphoma (NHL) in first remission
- •Relapsed or refractory NHL
- •Hodgkin's lymphoma (HL) beyond first remission
- •Performance status by Karnofsky of >= 70% or Lansky > 70% for patients < 16 years of age
- •Human leukocyte antigen (HLA) mismatched related or unrelated donor identified 8/10 or 9/10
- •Willingness to take oral medications during the transplantation period
- •Willingness and ability to sign a written informed consent (assent if applicable)
排除标准
- •Prior myeloablative allogeneic or autologous HSCT
- •Human immunodeficiency virus (HIV) infection
- •Pregnant or lactating females
- •Evidence of uncontrolled active infection
- •Down syndrome
- •Serum creatinine (CR) < 1.5mg/dl or 24 hour CR clearance < 50 ml/min
- •Direct bilirubin > 2 x upper limit of normal (ULN)
- •Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2 x ULN
- •Carbon monoxide diffusing capability test (DLCO) > 60% predicted and in children- room air oxygen saturation > 92%
- •Left ventricular ejection fraction < 45% and in children-shortening fraction < 26%
- •Fasting cholesterol > 300 mg/dl or triglycerides > 300 while on lipid lowering agents
- •Patients who have received an investigational drug within 30 days of enrollment in study
- •Patients with prior malignancies except basal cell carcinoma or treated carcinoma in-situ; cancer treated with curative intent > 5 years will be allowed; cancer treatment with curative intent =< 5 years will not be allowed
研究组 & 干预措施
Treatment (sirolimus, HSCT, MMF)
Patients receive sirolimus PO starting on day -3, 3 times a week during hospitalization and then once a week for up to 6 months. Patients undergo HSCT on day 0. Patients also receive mycophenolate mofetil IV or PO TID on days 1-180. Treatment continues in the absence of disease progression or unacceptable toxicity.
干预措施: Allogeneic Hematopoietic Stem Cell Transplantation (Procedure)
Treatment (sirolimus, HSCT, MMF)
Patients receive sirolimus PO starting on day -3, 3 times a week during hospitalization and then once a week for up to 6 months. Patients undergo HSCT on day 0. Patients also receive mycophenolate mofetil IV or PO TID on days 1-180. Treatment continues in the absence of disease progression or unacceptable toxicity.
干预措施: Laboratory Biomarker Analysis (Other)
Treatment (sirolimus, HSCT, MMF)
Patients receive sirolimus PO starting on day -3, 3 times a week during hospitalization and then once a week for up to 6 months. Patients undergo HSCT on day 0. Patients also receive mycophenolate mofetil IV or PO TID on days 1-180. Treatment continues in the absence of disease progression or unacceptable toxicity.
干预措施: Mycophenolate Mofetil (Drug)
Treatment (sirolimus, HSCT, MMF)
Patients receive sirolimus PO starting on day -3, 3 times a week during hospitalization and then once a week for up to 6 months. Patients undergo HSCT on day 0. Patients also receive mycophenolate mofetil IV or PO TID on days 1-180. Treatment continues in the absence of disease progression or unacceptable toxicity.
干预措施: Sirolimus (Drug)
结局指标
主要结局
Incidence of acute GvHD grade 3 & 4, according to the Glucksberg staging criteria
时间窗: Up to 100 days post-transplant
Statistical analysis results will be reported using summary tables, figures, and data listings. Continuous variables will be summarized using the mean, standard deviation, median, minimum, and maximum.
次要结局
- Incidence of thrombotic microangiopathy defined according to the bone marrow transplant clinical trials network toxicity committee(Up to 100 days)
- Time to neutrophil engraftment defined as first of 3 consecutive days with the absolute neutrophil count is > 500/ul in the peripheral blood(Baseline to up to 100 days)
- Time to platelet engraftment defined as the first day of a minimum of three consecutive measurements on different days when platelet count > 50,000/mm^3 and patient is transfusion-independent for a minimum of 7 days(Baseline to up to 100 days)
- Incidence of venous-occlusive disease (VOD) using Modified Seattle Criteria(Up to 100 days)
- Severity of mucositis determined by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03(Up to 100 days)