A Randomized, Double-blind, Placebo-controlled Trial to Evaluate Palifermin (rHuKGF) in the Reduction of Acute Graft Versus Host Disease in Subjects With Hematologic Malignancies Undergoing Allogeneic Marrow/PBPC Transplantation
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 155
- 主要终点
- Number of Participants With Severe (Grade 3 and 4) Acute Graft Versus Host Disease (GVHD)
研究概览
简要总结
The main purpose of this study is to evaluate the effect of palifermin versus placebo in the reduction of severe acute graft versus host disease (GVHD) and severe oral mucositis.
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
- Double (Participant, Investigator)
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
- •Subjects with hematologic malignancies (including myelodysplastic syndromes [MDS]) who are considered eligible for Cyclophosphamide (Cy)/Total Body Irradiation(TBI) +/- Etoposide (VP-16); Total Body Irradiation(TBI)/ Etoposide(VP-16); Melphalan(Mel) / Total Body Irradiation(TBI); Busulfan(Bu)/ Cyclophosphamide(Cy); Busulfan(Bu)/ Melphalan (Mel); or Fludarabine(Flu)/ Melphalan(Mel) conditioning therapy with allogeneic stem cell support
- •Subjects with a 6/6 Human Leukocyte Antigen (HLA)-matched family member or unrelated donor who would provide donor marrow/ peripheral progenitor stem cells. [For unrelated matched donors, molecular typing of class I and class II is mandatory]
- •Karnofsky Performance Status >= 70%
- •18 years of age or older at time of informed consent
- •Before any study-specific procedure, the appropriate written informed consent must be obtained
排除标准
- •Cancer other than Non-Hodgkin's lymphoma, Hodgkin's disease, acute myelogenous leukemia, acute lymphoblastic leukemia, chronic myelogenous leukemia, chronic lymphocytic leukemia, myelodysplastic syndrome or multiple myeloma (except: adequately treated basal cell carcinoma of the skin)
- •Prior autologous or allogeneic bone marrow or peripheral blood stem cell transplantation
- •Previous use of palifermin
- •Current active infection (including human immunodeficiency virus (HIV) and hepatitis) or oral mucositis
- •Congestive heart failure as defined by New York Heart Association class III or IV
- •Graft T-cell depletion for Graft-versus-host disease (GVHD) prophylaxis
- •Inadequate renal function (serum creatinine > 1.5x the upper limit of normal per the institutional guidelines or clearance < 40 ml/min adjusted for age)
- •Inadequate liver function (total bilirubin > 1.5x the upper limit of normal, aspartate aminotransferase (AST) > 3x upper limit of normal and/or alanine aminotransferase (ALT) > 3x upper limit of normal per the institutional guidelines)
- •Inadequate pulmonary function as measured by a corrected DLCO (diffusing capacity of the lung for carbon monoxide lung function test) <50% of predicted
- •Subject is currently enrolled in or has not yet completed at least 30 days since ending other investigational device or drug trial(s), or subject is receiving other investigational agent(s)
- •Subject of child-bearing potential is evidently pregnant (e.g. positive human chorionic gonadotropin- HCG test) or is breast feeding during Part A of the study
- •Subject or partner of subject is not using or refuses to use adequate contraceptive precautions during Part A of the study
- •Subject has known sensitivity to any of the products to be administered during dosing including Escherichia coli-derived products
- •Subject was previously randomized into this study
- •Subject will not be available for follow-up assessments
- •Subject has any kind of disorder that compromises the ability of the subject to give written informed consent and/or to comply with study procedures
研究组 & 干预措施
Palifermin
Palifermin 60 μg/kg administered daily on 3 consecutive days prior to the day of start of the conditioning regimen and 180 μg/kg administered once prior to transplant and at least 96 hours from last palifermin dose of 60 μg/kg. Participants received conditioning therapy starting at least 24 hours after the last 60 μg dose of palifermin. Allogeneic stem cell transplant occurred on Day 0. Methotrexate dosing began at least 24 hours after the 180 μg/kg dose of palifermin on Days 1, 3, 6 and (planned) 11 administration (toxicity allowing) at doses of 15, 10, 10 and 10 mg/m^2 respectively.
干预措施: Palifermin (Drug)
Palifermin
Palifermin 60 μg/kg administered daily on 3 consecutive days prior to the day of start of the conditioning regimen and 180 μg/kg administered once prior to transplant and at least 96 hours from last palifermin dose of 60 μg/kg. Participants received conditioning therapy starting at least 24 hours after the last 60 μg dose of palifermin. Allogeneic stem cell transplant occurred on Day 0. Methotrexate dosing began at least 24 hours after the 180 μg/kg dose of palifermin on Days 1, 3, 6 and (planned) 11 administration (toxicity allowing) at doses of 15, 10, 10 and 10 mg/m^2 respectively.
干预措施: Conditioning Regimen (Other)
Palifermin
Palifermin 60 μg/kg administered daily on 3 consecutive days prior to the day of start of the conditioning regimen and 180 μg/kg administered once prior to transplant and at least 96 hours from last palifermin dose of 60 μg/kg. Participants received conditioning therapy starting at least 24 hours after the last 60 μg dose of palifermin. Allogeneic stem cell transplant occurred on Day 0. Methotrexate dosing began at least 24 hours after the 180 μg/kg dose of palifermin on Days 1, 3, 6 and (planned) 11 administration (toxicity allowing) at doses of 15, 10, 10 and 10 mg/m^2 respectively.
干预措施: Allogeneic stem cell transplant (Procedure)
Palifermin
Palifermin 60 μg/kg administered daily on 3 consecutive days prior to the day of start of the conditioning regimen and 180 μg/kg administered once prior to transplant and at least 96 hours from last palifermin dose of 60 μg/kg. Participants received conditioning therapy starting at least 24 hours after the last 60 μg dose of palifermin. Allogeneic stem cell transplant occurred on Day 0. Methotrexate dosing began at least 24 hours after the 180 μg/kg dose of palifermin on Days 1, 3, 6 and (planned) 11 administration (toxicity allowing) at doses of 15, 10, 10 and 10 mg/m^2 respectively.
干预措施: Methotrexate (Drug)
Placebo
Placebo to palifermin 60 μg/kg administered daily on 3 consecutive days prior to the day of start of the conditioning regimen and placebo to palifermin 180 μg/kg once prior to transplant and at least 96 hours from previous placebo to palifermin 60 μg/kg dose. Participants received conditioning therapy starting at least 24 hours after the last 60 μg/kg dose of placebo to palifermin. Allogeneic stem cell transplant occurred on Day 0. Methotrexate dosing began at least 24 hours after the dose of placebo to palifermin 180 μg/kg on Days 1, 3, 6 and (planned) 11 administration (toxicity allowing) at doses of 15, 10, 10 and 10 mg/m^2 respectively.
干预措施: Placebo (Drug)
Placebo
Placebo to palifermin 60 μg/kg administered daily on 3 consecutive days prior to the day of start of the conditioning regimen and placebo to palifermin 180 μg/kg once prior to transplant and at least 96 hours from previous placebo to palifermin 60 μg/kg dose. Participants received conditioning therapy starting at least 24 hours after the last 60 μg/kg dose of placebo to palifermin. Allogeneic stem cell transplant occurred on Day 0. Methotrexate dosing began at least 24 hours after the dose of placebo to palifermin 180 μg/kg on Days 1, 3, 6 and (planned) 11 administration (toxicity allowing) at doses of 15, 10, 10 and 10 mg/m^2 respectively.
干预措施: Conditioning Regimen (Other)
Placebo
Placebo to palifermin 60 μg/kg administered daily on 3 consecutive days prior to the day of start of the conditioning regimen and placebo to palifermin 180 μg/kg once prior to transplant and at least 96 hours from previous placebo to palifermin 60 μg/kg dose. Participants received conditioning therapy starting at least 24 hours after the last 60 μg/kg dose of placebo to palifermin. Allogeneic stem cell transplant occurred on Day 0. Methotrexate dosing began at least 24 hours after the dose of placebo to palifermin 180 μg/kg on Days 1, 3, 6 and (planned) 11 administration (toxicity allowing) at doses of 15, 10, 10 and 10 mg/m^2 respectively.
干预措施: Allogeneic stem cell transplant (Procedure)
Placebo
Placebo to palifermin 60 μg/kg administered daily on 3 consecutive days prior to the day of start of the conditioning regimen and placebo to palifermin 180 μg/kg once prior to transplant and at least 96 hours from previous placebo to palifermin 60 μg/kg dose. Participants received conditioning therapy starting at least 24 hours after the last 60 μg/kg dose of placebo to palifermin. Allogeneic stem cell transplant occurred on Day 0. Methotrexate dosing began at least 24 hours after the dose of placebo to palifermin 180 μg/kg on Days 1, 3, 6 and (planned) 11 administration (toxicity allowing) at doses of 15, 10, 10 and 10 mg/m^2 respectively.
干预措施: Methotrexate (Drug)
结局指标
主要结局
Number of Participants With Severe (Grade 3 and 4) Acute Graft Versus Host Disease (GVHD)
时间窗: From transplant (Day 0) until Day 100
GVHD was graded using the modified Keystone Criteria weekly during the first 2 months after stem cell infusion, then every other week until Day 100. Severity was determined clinically (based on physical exam and laboratory serum values) and from biopsies of affected organs whenever possible. The degree of GVHD in individual organs was scored by at least 2 assessors. Grade 3 GVHD = total bilirubin 3.1 - 15.0 mg/dL or ≥ 1000 mL/day diarrhea or severe abdominal pain with/without ileus. Grade 4 GVHD = skin involvement with bullous formation or total bilirubin \> 15.0 mg/dL.
次要结局
- Number of Participants With Grade 2 to 4 Acute Graft Versus Host Disease (GVHD)(From transplant (Day 0) until Day 100)
- Number of Participants With Day 11 Methotrexate Graft Versus Host Disease Prophylaxis Administration(Day 11)
- Number of Participants With Severe (Grade 3 or 4) Oral Mucositis(From transplant (Day 0) until Day 100)
- Duration of Severe Oral Mucositis (WHO Grade 3 and 4)(From transplant (Day 0) until Day 100)
- Number of Participants With Parenteral or Transdermal Opioid Analgesic Use(From transplant (Day 0) until Day 100)
- Duration of Hospitalization(From transplant (Day 0) until Day 100)
- Area Under the Curve (AUC) of Mouth and Throat Soreness Score(The first day of study drug administration through Day 28.)