High-dose Gemcitabine, Busulfan and Melphalan With Autologous Hematopoietic-Cell Support for Patients With Poor-Risk Myeloma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 75
- 试验地点
- 1
- 主要终点
- Participants Who Had Measurable Disease at Time of Transplant and Achieved a Stringent Complete Remission
研究概览
简要总结
The goal of this clinical research study is to learn if the combination of gemcitabine, busulfan, and melphalan, when given before a stem cell transplant, can help to control refractory myeloma. The safety of this study treatment will also be studied.
详细描述
Study Drugs:
Busulfan and melphalan are designed to bind to the DNA (genetic material) of cells, which may cause cancer cells to die. They are commonly used in stem cell transplantation.
Gemcitabine is designed to disrupt the growth of cancer cells, which may cause cancer cells to die. It may help to increase the effect of busulfan and melphalan on cancer cells by not allowing these cells to repair the DNA damage caused by busulfan or melphalan.
Busulfan Test Dose:
You will receive a test dose of busulfan by vein over about 60 minutes. This low-level test dose of busulfan is to check how the level of busulfan in your blood levels changes over time. This information will be used to decide the next dose needed to reach the target blood level that matches your body size. You will most likely receive this as an outpatient during the week before you are admitted to the hospital. If it cannot be given as an outpatient, you will be admitted to the hospital on Day -11 (11 days before your stem cells are returned to your body) and the test dose will be given on Day -10.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18 to 70 years.
- •Patients with myeloma treated with first-line therapy including lenalidomide, bortezomib or thalidomide, and one or more of the following: 2.1) M paraprotein greater than 1 g/dL at HDC. 2.2) Less than partial response to first-line therapy. 2.3) Relapse after first-line therapy. 2.4) Relapse after a prior autologous stem-cell transplant.
- •Adequate renal function, as defined by serum creatinine </=1.8 mg/dL and/or estimated serum creatinine clearance >/=50 ml/min
- •Adequate hepatic function, as defined by serum glutamate oxaloacetate transaminase (SGOT) and/or serum glutamate pyruvate transaminase (SGPT) </=3 x upper limit of normal; serum bilirubin and alkaline phosphatase </=2 x upper limit of normal, unless proven to be due to disease involvement.
- •Adequate pulmonary function with forced expiratory volume at one second (FEV1), forced vital capacity (FVC) and diffusing capacity of lung for carbon monoxide (DLCO) >/=50% of expected corrected for hemoglobin and/or volume.
- •Adequate cardiac function with left ventricular ejection fraction >/=40%. No uncontrolled arrhythmias or symptomatic cardiac disease.
- •Zubrod performance status <
- •Negative Beta human chorionic gonadotropin (HCG) text in a woman with child-bearing potential, defined as not post-menopausal for 12 months or no previous surgical sterilization
排除标准
- •Patients with grade >/= 3 non-hematologic toxicity from previous therapy that has not resolved to </= grade
- •Patients with prior whole brain irradiation
- •Patients with active hepatitis B, either active carrier (HBsAg +) or viremic (HBV DNA >/=10,000 copies/mL, or >/= 2,000 IU/mL).
- •Evidence of either cirrhosis or stage 3-4 liver fibrosis in patients with chronic hepatitis C or positive hepatitis C serology.
- •Active infection requiring parenteral antibiotics.
- •HIV infection, unless the patient is receiving effective antiretroviral therapy with undetectable viral load and normal cluster of differentiation 4 (CD4) counts
- •Patients having received radiation therapy to head and neck (excluding eyes), and internal organs of chest, abdomen or pelvis in the month prior to enrollment.
研究组 & 干预措施
GemBuMel
Gemcitabine 1875 mg/m^2 IV (75 mg/ m2 bolus followed by 1800 mg/m^2 over 3 hours) on Day -8 and Day -3 as an outpatient or inpatient.
Busulfan 32 mg/m2 test dose with PKs as outpatient before Day -12, or as an inpatient on Day -10.
Busulfan area under curve (AUC) 4,000 by vein on Days -8 to -5 as an outpatient or inpatient.
Melphalan 60 mg/m^2 IV on Days -3 and -2 over 30 minutes on both days as an outpatient or inpatient.
Palifermin 60 micrograms/kg infused as an IVP (by vein) over 15-30 seconds Days -12 to -10 and Days 0 to +2 as an outpatient.
Palifermin 60 micrograms/kg by vein on Days -13 to -11 and on Days 0, +1 and +2 as in inpatient.
Dexamethasone 8 mg IV twice a day by vein over 15 minutes Days -9 through -2 as an outpatient or inpatient. G-CSF 5 mcg/kg/day subcutaneously beginning on Day +5 and continuing until neutrophil recovery is documented.
Stem Cell Transplant: On Day 0, stem cells returned to body by vein over 30-60 minutes.
干预措施: Gemcitabine (Drug)
GemBuMel
Gemcitabine 1875 mg/m^2 IV (75 mg/ m2 bolus followed by 1800 mg/m^2 over 3 hours) on Day -8 and Day -3 as an outpatient or inpatient.
Busulfan 32 mg/m2 test dose with PKs as outpatient before Day -12, or as an inpatient on Day -10.
Busulfan area under curve (AUC) 4,000 by vein on Days -8 to -5 as an outpatient or inpatient.
Melphalan 60 mg/m^2 IV on Days -3 and -2 over 30 minutes on both days as an outpatient or inpatient.
Palifermin 60 micrograms/kg infused as an IVP (by vein) over 15-30 seconds Days -12 to -10 and Days 0 to +2 as an outpatient.
Palifermin 60 micrograms/kg by vein on Days -13 to -11 and on Days 0, +1 and +2 as in inpatient.
Dexamethasone 8 mg IV twice a day by vein over 15 minutes Days -9 through -2 as an outpatient or inpatient. G-CSF 5 mcg/kg/day subcutaneously beginning on Day +5 and continuing until neutrophil recovery is documented.
Stem Cell Transplant: On Day 0, stem cells returned to body by vein over 30-60 minutes.
干预措施: Palifermin (Drug)
GemBuMel
Gemcitabine 1875 mg/m^2 IV (75 mg/ m2 bolus followed by 1800 mg/m^2 over 3 hours) on Day -8 and Day -3 as an outpatient or inpatient.
Busulfan 32 mg/m2 test dose with PKs as outpatient before Day -12, or as an inpatient on Day -10.
Busulfan area under curve (AUC) 4,000 by vein on Days -8 to -5 as an outpatient or inpatient.
Melphalan 60 mg/m^2 IV on Days -3 and -2 over 30 minutes on both days as an outpatient or inpatient.
Palifermin 60 micrograms/kg infused as an IVP (by vein) over 15-30 seconds Days -12 to -10 and Days 0 to +2 as an outpatient.
Palifermin 60 micrograms/kg by vein on Days -13 to -11 and on Days 0, +1 and +2 as in inpatient.
Dexamethasone 8 mg IV twice a day by vein over 15 minutes Days -9 through -2 as an outpatient or inpatient. G-CSF 5 mcg/kg/day subcutaneously beginning on Day +5 and continuing until neutrophil recovery is documented.
Stem Cell Transplant: On Day 0, stem cells returned to body by vein over 30-60 minutes.
干预措施: Dexamethasone (Drug)
GemBuMel
Gemcitabine 1875 mg/m^2 IV (75 mg/ m2 bolus followed by 1800 mg/m^2 over 3 hours) on Day -8 and Day -3 as an outpatient or inpatient.
Busulfan 32 mg/m2 test dose with PKs as outpatient before Day -12, or as an inpatient on Day -10.
Busulfan area under curve (AUC) 4,000 by vein on Days -8 to -5 as an outpatient or inpatient.
Melphalan 60 mg/m^2 IV on Days -3 and -2 over 30 minutes on both days as an outpatient or inpatient.
Palifermin 60 micrograms/kg infused as an IVP (by vein) over 15-30 seconds Days -12 to -10 and Days 0 to +2 as an outpatient.
Palifermin 60 micrograms/kg by vein on Days -13 to -11 and on Days 0, +1 and +2 as in inpatient.
Dexamethasone 8 mg IV twice a day by vein over 15 minutes Days -9 through -2 as an outpatient or inpatient. G-CSF 5 mcg/kg/day subcutaneously beginning on Day +5 and continuing until neutrophil recovery is documented.
Stem Cell Transplant: On Day 0, stem cells returned to body by vein over 30-60 minutes.
干预措施: Busulfan (Drug)
GemBuMel
Gemcitabine 1875 mg/m^2 IV (75 mg/ m2 bolus followed by 1800 mg/m^2 over 3 hours) on Day -8 and Day -3 as an outpatient or inpatient.
Busulfan 32 mg/m2 test dose with PKs as outpatient before Day -12, or as an inpatient on Day -10.
Busulfan area under curve (AUC) 4,000 by vein on Days -8 to -5 as an outpatient or inpatient.
Melphalan 60 mg/m^2 IV on Days -3 and -2 over 30 minutes on both days as an outpatient or inpatient.
Palifermin 60 micrograms/kg infused as an IVP (by vein) over 15-30 seconds Days -12 to -10 and Days 0 to +2 as an outpatient.
Palifermin 60 micrograms/kg by vein on Days -13 to -11 and on Days 0, +1 and +2 as in inpatient.
Dexamethasone 8 mg IV twice a day by vein over 15 minutes Days -9 through -2 as an outpatient or inpatient. G-CSF 5 mcg/kg/day subcutaneously beginning on Day +5 and continuing until neutrophil recovery is documented.
Stem Cell Transplant: On Day 0, stem cells returned to body by vein over 30-60 minutes.
干预措施: Melphalan (Drug)
GemBuMel
Gemcitabine 1875 mg/m^2 IV (75 mg/ m2 bolus followed by 1800 mg/m^2 over 3 hours) on Day -8 and Day -3 as an outpatient or inpatient.
Busulfan 32 mg/m2 test dose with PKs as outpatient before Day -12, or as an inpatient on Day -10.
Busulfan area under curve (AUC) 4,000 by vein on Days -8 to -5 as an outpatient or inpatient.
Melphalan 60 mg/m^2 IV on Days -3 and -2 over 30 minutes on both days as an outpatient or inpatient.
Palifermin 60 micrograms/kg infused as an IVP (by vein) over 15-30 seconds Days -12 to -10 and Days 0 to +2 as an outpatient.
Palifermin 60 micrograms/kg by vein on Days -13 to -11 and on Days 0, +1 and +2 as in inpatient.
Dexamethasone 8 mg IV twice a day by vein over 15 minutes Days -9 through -2 as an outpatient or inpatient. G-CSF 5 mcg/kg/day subcutaneously beginning on Day +5 and continuing until neutrophil recovery is documented.
Stem Cell Transplant: On Day 0, stem cells returned to body by vein over 30-60 minutes.
干预措施: Stem Cell Transplant (Procedure)
GemBuMel
Gemcitabine 1875 mg/m^2 IV (75 mg/ m2 bolus followed by 1800 mg/m^2 over 3 hours) on Day -8 and Day -3 as an outpatient or inpatient.
Busulfan 32 mg/m2 test dose with PKs as outpatient before Day -12, or as an inpatient on Day -10.
Busulfan area under curve (AUC) 4,000 by vein on Days -8 to -5 as an outpatient or inpatient.
Melphalan 60 mg/m^2 IV on Days -3 and -2 over 30 minutes on both days as an outpatient or inpatient.
Palifermin 60 micrograms/kg infused as an IVP (by vein) over 15-30 seconds Days -12 to -10 and Days 0 to +2 as an outpatient.
Palifermin 60 micrograms/kg by vein on Days -13 to -11 and on Days 0, +1 and +2 as in inpatient.
Dexamethasone 8 mg IV twice a day by vein over 15 minutes Days -9 through -2 as an outpatient or inpatient. G-CSF 5 mcg/kg/day subcutaneously beginning on Day +5 and continuing until neutrophil recovery is documented.
Stem Cell Transplant: On Day 0, stem cells returned to body by vein over 30-60 minutes.
干预措施: G-CSF (Drug)
结局指标
主要结局
Participants Who Had Measurable Disease at Time of Transplant and Achieved a Stringent Complete Remission
时间窗: 100 days post-transplant
Stringent complete remission was defined as negative immunofixation on the serum and urine, disappearance of any soft tissue plasmacytomas, 5% or fewer plasma cells in bone marrow, normal free light chain ratio, and the absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence.
次要结局
- Overall Survival(From date of transplant until the date of death from any cause, assessed up to 2 years)
- Percent of Participants Dying From Treatment-Related Complications(From date of transplant until the date of death from treatment-related complications, assessed up to 2 years)
- Progression-free Survival (PFS)(From date of transplant until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years.)