Tacrolimus, Mini-dose Methotrexate and Mycophenolate Mofetil Versus Tacrolimus and Methotrexate for the Prevention of Acute Graft-versus-Host-Disease
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 101
- 试验地点
- 1
- 主要终点
- Percentage of Severe (Grade 3-4) Mucositis Graded According to the World Health Organization (WHO) Grading Scale
研究概览
简要总结
This randomized clinical trial studies standard GVHD prophylaxis with tacrolimus and methotrexate compared to tacrolimus, mycophenolate mofetil and a reduced-dose methotrexate in patients with hematologic malignancies undergoing allogeneic hematopoietic cell transplant. Both mycophenolate mofetil and reduced-dose methotrexate, in combination with a calcineurin inhibitor, have been shown to be safe and effective in GVHD prevention with less toxicity than standard dose methotrexate. It is not yet known, however, whether this combination of mycophenolate mofetil and reduced-dose methotrexate with tacrolimus is more effective than tacrolimus and standard dose methotrexate in preventing GVHD.
详细描述
Study Design This is a prospective randomized trial to determine the effectiveness of different doses of GVHD prophylaxis on mucositis, engraftment and aGVHD. Study consists of two study groups of 50 subjects each.
Group A will receive Tac and MTX (15 mg/m2 day +1, 10 mg/m2 day +3, +6, +11). Group B will receive Tac, Mini-dose MTX (5 mg/m2 on day +1, +3, +6) and MMF.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 盲法
- None
入排标准
- 年龄范围
- — 至 70 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must have one of the following documented diseases:
- •Chronic myelogenous leukemia
- •Chronic lymphocytic leukemia
- •Multiple myeloma
- •Myelodysplasia
- •Myeloproliferative disorder
- •Non-Hodgkin's lymphoma
- •Hodgkin's disease
- •Acute myelogenous leukemia
- •Acute lymphoblastic leukemia
- •Acute biphenotypic leukemia
- •Patients must be undergoing a myeloablative allogeneic hematopoietic cell transplant with one of the following conditioning regimens:
- •Busulfan (≥ 12.8 mg/kg IV or PO) and cyclophosphamide (≥ 120 mg/kg)
- •-- Busulfan dose may be adjusted according to pharmacokinetics targeting a daily AUC of 5000 μmol-min/L, per institution standard of practice.
- •Total body irradiation (TBI) (≥ 1200 cGy) and etoposide (60 mg/kg)
- •TBI (≥ 1200 cGy) and cyclophosphamide (120 mg/kg)
- •Patient must have achieved and be in complete morphologic remission prior to starting conditioning regimen
- •Patient's donor must be a related or unrelated human leukocyte antigen (HLA) 8/8 allele-level match (HLA-A, B, C and DRB1)
- •Adult patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; pediatric patients must have Lansky score ≥ 60%
- •Patients must have a life expectancy of 100 days
- •Patients must sign written informed consent
排除标准
- •Patients who have undergone any prior transplant
- •Patients who are seropositive for human immunodeficiency virus (HIV)
- •Patients with any medical illness or concurrent psychiatric illness which, in the investigators' opinion, cannot be adequately controlled with appropriate therapy
- •Patients who are pregnant or lactating
研究组 & 干预措施
Group A (tacrolimus, methotrexate)
Participants receive tacrolimus IV over 24 hours beginning on day -1 (or tacrolimus orally beginning on day -3) and then PO BID after engraftment with a taper from day 100 to day 180 (in the absence of GVHD). Patients also receive methotrexate IV on days 1, 3, 6, and 11.
干预措施: tacrolimus (Drug)
Group A (tacrolimus, methotrexate)
Participants receive tacrolimus IV over 24 hours beginning on day -1 (or tacrolimus orally beginning on day -3) and then PO BID after engraftment with a taper from day 100 to day 180 (in the absence of GVHD). Patients also receive methotrexate IV on days 1, 3, 6, and 11.
干预措施: methotrexate (Drug)
Group B (tacrolimus, methotrexate, mycophenolate mofetil)
Patients receive tacrolimus as in group A and methotrexate (low dose) IV on days 1, 3, and 6. Patients also receive oral mycophenolate mofetil BID beginning on day 1, with a taper from day 45 to day 100 (in the absence of GVHD).
干预措施: tacrolimus (Drug)
Group B (tacrolimus, methotrexate, mycophenolate mofetil)
Patients receive tacrolimus as in group A and methotrexate (low dose) IV on days 1, 3, and 6. Patients also receive oral mycophenolate mofetil BID beginning on day 1, with a taper from day 45 to day 100 (in the absence of GVHD).
干预措施: Mycophenolate mofetil (Drug)
Group B (tacrolimus, methotrexate, mycophenolate mofetil)
Patients receive tacrolimus as in group A and methotrexate (low dose) IV on days 1, 3, and 6. Patients also receive oral mycophenolate mofetil BID beginning on day 1, with a taper from day 45 to day 100 (in the absence of GVHD).
干预措施: Methotrexate (low dose) (Drug)
结局指标
主要结局
Percentage of Severe (Grade 3-4) Mucositis Graded According to the World Health Organization (WHO) Grading Scale
时间窗: Up to day 28
Participants (percentage of) will be graded three times per week through day 28 of the study. Incidence will be compared through Wilcoxon rank sum tests. The WHO grading scale for mucositis is scaled depending on the severity of mucositis symptoms, with a lower stage associated with a better outcome and greater stages associated with worse outcomes. The staging is as follows: Stage 0: None Stage 1 (mild): Oral soreness, erythema Stage 2 (moderate): Oral erythema, ulcers, solid diet tolerated Stage 3 (severe): Oral ulcers, liquid diet only Stage 4 (life-threatening): Oral alimentation impossible
Time to Neutrophil Engraftment
时间窗: Up to 28 days
The number of days to reach a neutrophil count of greater than or equal to 500/ul for three consecutive laboratory values obtained on different days. The day of engraftment will be the first day of the three consecutive laboratory values.
Cumulative Incidence of Participants With Acute GVHD
时间窗: Day 7- Day 100
Acute GVHD by grade will be estimated using cumulative incidence methods and compared using the Gray test. A lower clinical grade and/or stage of GVHD corresponds to a better participant outcome and a higher grade corresponds to a worse participant outcome. Grading is as follows: Grade 0: No stage 1-4 of any organ Grade 1: Stage 1-2 skin without liver, upper GI, or lower GI involvement. Grade 2: Stage 3 rash and/or stage 1 liver and/or stage 1 upper GI and/or stage 1 lower GI. Grade 3: Stage 2-3 liver and/or stage 2-3 lower GI, with stage 0-3 skin and/or stage 0-1 upper GI. Grade 4: Stage 4 skin, liver, or lower GI involvement, with stage 0-1 upper GI. A greater stage of GVHD involves worsening end-organ involvement and worse participant outcomes based on the skin, liver, lower GI, and upper GI.
Time to Platelet Engraftment
时间窗: The date the participant engrafts, up to 28 days
The number of days to reach a platelet count of greater than or equal to 20,000/ul for three consecutive laboratory values obtained on different days, independent of platelet transfusions the prior 7 days. The day of engraftment will be the first day of the three consecutive laboratory values. For cases of delayed engraftment beyond 28 days, results will be recorded once the participant engrafts.
次要结局
- Overall Survival(Up to 1 year)
- Incidence of Hepatotoxicity as Measured by Veno-occlusive Disease (VOD)(Up to day +100)
- Incidence of Hepatotoxicity as Measured by Elevated Liver Enzymes(Up to day +100)
- Incidence of Pulmonary Toxicity Measured by Pulmonary Edema(Up to day +180)
- Length of Time on Continuous Infusion Narcotics(up to +28 day)
- Incidence of Infection(Up to day +100)
- Incidence of Pulmonary Toxicity Measured by Pulmonary Hemorrhage(Up to day +180)
- Incidence of Pulmonary Toxicity Measured by Respiratory Failure(Up to day +180)
- Length of Hospitalization(Date of transplant to date of discharge, assessed up to 1 year)
- Percentage of Participants Using Total Parenteral Nutrition (TPN) Within 100 Days(Up to day 100)
- Progression-free Survival(Up to 1 year)
- Incidence of Hepatotoxicity as Measured by Bilirubin(Up to day +100)
- Incidence of Chronic GVHD(at 12 months)
- Incidence of Nephrotoxicity(Up to day +100)