Infusional Gemcitabine and High-dose Melphalan (HDM) Conditioning Prior to (ASCT) Autologous Stem Cell Transplantation for Patients With Relapsed/Refractory Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Progression free survival of relapsed/refractory lymphoma patients treated with infusional gemcitabine, high dose melphalan (Gem-Mel) and ASCT
研究概览
简要总结
Objective of study: To evaluate the safety and efficacy of infusional gemcitabine prior to HDM (high-dose melphalan) as HDCT (High Dose Chemotherapy) followed by autologous stem cell transplantation in patients with relapsed/refractory lymphoma.
详细描述
High-dose chemotherapy with autologous stem cell transplantation is the current standard of care for patients with chemosensitive relapsed Hodgkin's lymphoma and aggressive non-Hodgkin's lymphoma, and is an established effective therapy for patients with relapsed follicular lymphoma. Disease relapse remains a major problem, occurring in 50% of these patients, particularly in patients with primary refractory disease or other high-risk features. The addition of gemcitabine to single-agent melphalan as a high-dose conditioning regimen presents a promising combination that may lead to improvements in EFS (Event free survival). If this trial gives encouraging results, it may lead to a phase III trial evaluating this treatment strategy.
Drug exposure would be AUC (area under curve) and clinical factors would be things like obesity, renal function, disease characteristics.
We would be looking at the safety outcomes - i.e. adverse events as a measure of safety and tolerability. The adverse events would be non-hematological toxicities (any) and whether or not it is related to AUC. AUC in relationship to PFS (progression free survival) is also important (we want to know if we need to adjust dose to improve PFS).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Ability to provide written informed consent
- •Age over 18 years
- •Relapsed/refractory lymphoma after at least 1 prior chemotherapy treatment:
- •Hodgkin's lymphoma
- •Aggressive non-Hodgkin's lymphoma
- •Follicular lymphoma
- •Chemosensitive disease at time of transplantation (i.e. partial response or better to salvage chemotherapy)
- •ECOG (Eastern Cooperative Oncology Group) performance 0-2
- •Adequate organ function:
- •Cardiac: LVEF (left ventricular ejection fraction)>40%
- •Pulmonary: FEV1 (forced expiratory volume at one second) and DLCO (diffusing capacity of lung for carbon monoxide)>60% predicted
- •Renal: creatinine <150 µmol/L unless caused by ureteric obstruction from lymphoma
- •Liver: No evidence of cirrhosis. ALT (Alanine Aminotransferase) and bilirubin <2x upper limit of normal unless caused by biliary tract obstruction from lymphoma
排除标准
- •Clinically significant active infection
- •Active secondary central nervous system disease
- •Other serious co-morbid illness that would compromise study participation.
- •Pregnant or lactating females
- •Prior HDCT/ASCT
研究组 & 干预措施
Gemcitabine/Melphalan Condition + ASCT
Day -1 -
- IV gemcitabine 1.5-2.5 g/m2 (depending on dose level assigned) administered as a loading bolus of 75 mg/m2, followed by a continuous infusion of 10 mg/m2/min.
- immediately following gemcitabine - IV melphalan 200 mg/m2 over 5 minutes.
Day 0
•Stem cell infusion
Patients will be assigned a dose level using the continual reassessment method based on the toxicity data available at the time of their enrollment. The dosing will start at 1.5 g/m2 and will increase by 0.5 mg/m2 at each level to a maximum of 2.5 g/m2. Dose-limiting toxicity is defined as grade 3 mucositis or skin toxicity lasting more than 3 days before downgrading, or any grade 4 non-hematological toxicity.
干预措施: Gemcitabine (Drug)
Gemcitabine/Melphalan Condition + ASCT
Day -1 -
- IV gemcitabine 1.5-2.5 g/m2 (depending on dose level assigned) administered as a loading bolus of 75 mg/m2, followed by a continuous infusion of 10 mg/m2/min.
- immediately following gemcitabine - IV melphalan 200 mg/m2 over 5 minutes.
Day 0
•Stem cell infusion
Patients will be assigned a dose level using the continual reassessment method based on the toxicity data available at the time of their enrollment. The dosing will start at 1.5 g/m2 and will increase by 0.5 mg/m2 at each level to a maximum of 2.5 g/m2. Dose-limiting toxicity is defined as grade 3 mucositis or skin toxicity lasting more than 3 days before downgrading, or any grade 4 non-hematological toxicity.
干预措施: Melphalan (Drug)
Gemcitabine/Melphalan Condition + ASCT
Day -1 -
- IV gemcitabine 1.5-2.5 g/m2 (depending on dose level assigned) administered as a loading bolus of 75 mg/m2, followed by a continuous infusion of 10 mg/m2/min.
- immediately following gemcitabine - IV melphalan 200 mg/m2 over 5 minutes.
Day 0
•Stem cell infusion
Patients will be assigned a dose level using the continual reassessment method based on the toxicity data available at the time of their enrollment. The dosing will start at 1.5 g/m2 and will increase by 0.5 mg/m2 at each level to a maximum of 2.5 g/m2. Dose-limiting toxicity is defined as grade 3 mucositis or skin toxicity lasting more than 3 days before downgrading, or any grade 4 non-hematological toxicity.
干预措施: ASCT (Other)
结局指标
主要结局
Progression free survival of relapsed/refractory lymphoma patients treated with infusional gemcitabine, high dose melphalan (Gem-Mel) and ASCT
时间窗: 3 years
The goal is to improve overall 3-year PFS by 15% over what would be expected with standard conditioning regimens. Patients will be stratified into 3 groups according to disease: (a) relapsed/refractory Hodgkins's lymphoma, (b) relapsed/refractory aggressive non-Hodgkin's lymphoma, and (c) relapsed/refractory follicular lymphoma. Grade 3-4 non-hematological toxicity will be defined by the NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.
Grade 3-4 Hematological Toxicity
时间窗: 3 YEARS
Assessment of Dose-limiting toxicity is defined as grade 3 mucositis or skin toxicity lasting more than 3 days before downgrading, or any grade 4 non-hematological toxicity.
次要结局
- Evaluation of relation between drug exposure and non-hematological toxicity and progression free survival(3 years)
- Overall survival(3 Years)
- Cost Effectiveness(3 Years)
- Measure of Melphalan pharmacokinetics, AUC (area under curve)(3 Years)
- Evaluation of relationship between clinical factors and drug exposure in treatment of Gemcitabine/Melphalan with ASCT (autologous stem cell transplantation)(3 years)
- Safety Outcomes assessed adverse events as a measure of safety and tolerability(3 years)