Carfilzomib/SAHA Combined With High-Dose Gemcitabine/Busulfan/Melphalan With Autologous Stem Cell Transplant for Patients With Refractory/Relapsed Myeloma
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 主要终点
- Complete Remission (CR) Rate
研究概览
简要总结
The goal of this clinical research study is to learn if carfilzomib and vorinostat combined with gemcitabine, busulfan, and melphalan with a stem cell transplant will help to control multiple myeloma (MM). Researchers also want to learn about the safety and effectiveness of this combination.
详细描述
Busulfan Test Dose:
Participant 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 participant's blood changes over time. This information will be used to decide the next dose needed to reach the target blood level that matches participant's body size. Participant will most likely receive this as an outpatient during the week before they are admitted to the hospital. If it cannot be given to participant as an outpatient, they will be admitted to the hospital on Day -11 (11 days before participant's stem cells are returned to their body) and the test dose will be given on Day -10.
About 11 samples of blood (about 1 teaspoon each time) will be drawn for pharmacokinetic (PK) testing of busulfan. PK testing measures the amount of study drug in the body at different time points and will help the study doctor decide what participant's dose of busulfan in this study should be. These blood samples will be drawn at various timepoints before participant receives busulfan and over about the next 11 hours. The blood samples will be repeated again on the first day of high-dose busulfan treatment (Day -8). A temporary heparin lock line will be placed in participant's vein to lower the number of needle sticks needed for these draws. If it is not possible for the PK tests to be performed for technical or scheduling reasons, participant will receive the standard fixed dose of busulfan.
If participant receives the busulfan test dose as an outpatient:
On Days -12, -11, and -10, participant will receive palifermin by vein over about 30 seconds each day to help decrease the risk of side effects in the mouth and throat.
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18 to 65 years
- •Refractory or relapsed myeloma, defined as one or more of the following:
- •Patients with myeloma treated with first-line therapy including lenalidomide, bortezomib or thalidomide, and one or more of the following: a. Less than partial response to first-line therapy. b. Relapse after 1st line therapy.
- •High-risk disease, defined by del(13q) by conventional cytogenetics, or by del(17p), t(4;14), t(14;16), t(14;20) or 1q+ by FISH.
- •Relapse after a prior autologous stem-cell transplantation (ASCT).
- •Plasma cell leukemia.
- •Plasmablastic lymphoma.
- •Soft tissue plasmacytoma.
- •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 (SGOT) and/or serum glutamic-pyruvic 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 FEV1, FVC and 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 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
- •Prior whole brain irradiation.
- •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 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.
- •Autologous stem-cell transplant in the previous six months.
研究组 & 干预措施
Carfilzomib/SAHA + Gem/Bu/Mel + Auto Stem Cell Transplant SCT
Busulfan test dose of 32 mg/m2 by vein on Day -10 if inpatient, on Day -12 if outpatient, then AUC of 4,000 microMol.min on Days -8 to -5. Palifermin 60 microgram/kg by vein on Days -12 to -10 and Days 0, +1 and +2. SAHA 1,000 mg by mouth on Days -8 to -3. Gemcitabine loading dose of 75 mg/m2 followed by continuous infusion of the remaining dose of 1875 mg/m2 by vein on Days -8 and -3. Carfilzomib 27 mg/m2 by vein on Days -7 and -6, then on Days -2 and -1. SAHA 1,000 mg by mouth on Days -7 to -3. Melphalan 60 mg/m2 by vein on Days -3 and -2. Stem cell transplant on Day 0. Dexamethasone 8 mg by vein twice a day from Day -9 PM to Day -2 PM. Caphosol oral rinses 30 mL four times a day from Day -9 until discharge. Oral glutamine 15 g four times a day, swished, gargled and spit on Day -9 until discharge. Pyridoxine 100 mg by vein or mouth three times a day from Day -1.
干预措施: Carfilzomib (Drug)
Carfilzomib/SAHA + Gem/Bu/Mel + Auto Stem Cell Transplant SCT
Busulfan test dose of 32 mg/m2 by vein on Day -10 if inpatient, on Day -12 if outpatient, then AUC of 4,000 microMol.min on Days -8 to -5. Palifermin 60 microgram/kg by vein on Days -12 to -10 and Days 0, +1 and +2. SAHA 1,000 mg by mouth on Days -8 to -3. Gemcitabine loading dose of 75 mg/m2 followed by continuous infusion of the remaining dose of 1875 mg/m2 by vein on Days -8 and -3. Carfilzomib 27 mg/m2 by vein on Days -7 and -6, then on Days -2 and -1. SAHA 1,000 mg by mouth on Days -7 to -3. Melphalan 60 mg/m2 by vein on Days -3 and -2. Stem cell transplant on Day 0. Dexamethasone 8 mg by vein twice a day from Day -9 PM to Day -2 PM. Caphosol oral rinses 30 mL four times a day from Day -9 until discharge. Oral glutamine 15 g four times a day, swished, gargled and spit on Day -9 until discharge. Pyridoxine 100 mg by vein or mouth three times a day from Day -1.
干预措施: SAHA (Drug)
Carfilzomib/SAHA + Gem/Bu/Mel + Auto Stem Cell Transplant SCT
Busulfan test dose of 32 mg/m2 by vein on Day -10 if inpatient, on Day -12 if outpatient, then AUC of 4,000 microMol.min on Days -8 to -5. Palifermin 60 microgram/kg by vein on Days -12 to -10 and Days 0, +1 and +2. SAHA 1,000 mg by mouth on Days -8 to -3. Gemcitabine loading dose of 75 mg/m2 followed by continuous infusion of the remaining dose of 1875 mg/m2 by vein on Days -8 and -3. Carfilzomib 27 mg/m2 by vein on Days -7 and -6, then on Days -2 and -1. SAHA 1,000 mg by mouth on Days -7 to -3. Melphalan 60 mg/m2 by vein on Days -3 and -2. Stem cell transplant on Day 0. Dexamethasone 8 mg by vein twice a day from Day -9 PM to Day -2 PM. Caphosol oral rinses 30 mL four times a day from Day -9 until discharge. Oral glutamine 15 g four times a day, swished, gargled and spit on Day -9 until discharge. Pyridoxine 100 mg by vein or mouth three times a day from Day -1.
干预措施: Gemcitabine (Drug)
Carfilzomib/SAHA + Gem/Bu/Mel + Auto Stem Cell Transplant SCT
Busulfan test dose of 32 mg/m2 by vein on Day -10 if inpatient, on Day -12 if outpatient, then AUC of 4,000 microMol.min on Days -8 to -5. Palifermin 60 microgram/kg by vein on Days -12 to -10 and Days 0, +1 and +2. SAHA 1,000 mg by mouth on Days -8 to -3. Gemcitabine loading dose of 75 mg/m2 followed by continuous infusion of the remaining dose of 1875 mg/m2 by vein on Days -8 and -3. Carfilzomib 27 mg/m2 by vein on Days -7 and -6, then on Days -2 and -1. SAHA 1,000 mg by mouth on Days -7 to -3. Melphalan 60 mg/m2 by vein on Days -3 and -2. Stem cell transplant on Day 0. Dexamethasone 8 mg by vein twice a day from Day -9 PM to Day -2 PM. Caphosol oral rinses 30 mL four times a day from Day -9 until discharge. Oral glutamine 15 g four times a day, swished, gargled and spit on Day -9 until discharge. Pyridoxine 100 mg by vein or mouth three times a day from Day -1.
干预措施: Busulfan (Drug)
Carfilzomib/SAHA + Gem/Bu/Mel + Auto Stem Cell Transplant SCT
Busulfan test dose of 32 mg/m2 by vein on Day -10 if inpatient, on Day -12 if outpatient, then AUC of 4,000 microMol.min on Days -8 to -5. Palifermin 60 microgram/kg by vein on Days -12 to -10 and Days 0, +1 and +2. SAHA 1,000 mg by mouth on Days -8 to -3. Gemcitabine loading dose of 75 mg/m2 followed by continuous infusion of the remaining dose of 1875 mg/m2 by vein on Days -8 and -3. Carfilzomib 27 mg/m2 by vein on Days -7 and -6, then on Days -2 and -1. SAHA 1,000 mg by mouth on Days -7 to -3. Melphalan 60 mg/m2 by vein on Days -3 and -2. Stem cell transplant on Day 0. Dexamethasone 8 mg by vein twice a day from Day -9 PM to Day -2 PM. Caphosol oral rinses 30 mL four times a day from Day -9 until discharge. Oral glutamine 15 g four times a day, swished, gargled and spit on Day -9 until discharge. Pyridoxine 100 mg by vein or mouth three times a day from Day -1.
干预措施: Melphalan (Drug)
Carfilzomib/SAHA + Gem/Bu/Mel + Auto Stem Cell Transplant SCT
Busulfan test dose of 32 mg/m2 by vein on Day -10 if inpatient, on Day -12 if outpatient, then AUC of 4,000 microMol.min on Days -8 to -5. Palifermin 60 microgram/kg by vein on Days -12 to -10 and Days 0, +1 and +2. SAHA 1,000 mg by mouth on Days -8 to -3. Gemcitabine loading dose of 75 mg/m2 followed by continuous infusion of the remaining dose of 1875 mg/m2 by vein on Days -8 and -3. Carfilzomib 27 mg/m2 by vein on Days -7 and -6, then on Days -2 and -1. SAHA 1,000 mg by mouth on Days -7 to -3. Melphalan 60 mg/m2 by vein on Days -3 and -2. Stem cell transplant on Day 0. Dexamethasone 8 mg by vein twice a day from Day -9 PM to Day -2 PM. Caphosol oral rinses 30 mL four times a day from Day -9 until discharge. Oral glutamine 15 g four times a day, swished, gargled and spit on Day -9 until discharge. Pyridoxine 100 mg by vein or mouth three times a day from Day -1.
干预措施: Stem Cell Transplant (SCT) (Procedure)
Carfilzomib/SAHA + Gem/Bu/Mel + Auto Stem Cell Transplant SCT
Busulfan test dose of 32 mg/m2 by vein on Day -10 if inpatient, on Day -12 if outpatient, then AUC of 4,000 microMol.min on Days -8 to -5. Palifermin 60 microgram/kg by vein on Days -12 to -10 and Days 0, +1 and +2. SAHA 1,000 mg by mouth on Days -8 to -3. Gemcitabine loading dose of 75 mg/m2 followed by continuous infusion of the remaining dose of 1875 mg/m2 by vein on Days -8 and -3. Carfilzomib 27 mg/m2 by vein on Days -7 and -6, then on Days -2 and -1. SAHA 1,000 mg by mouth on Days -7 to -3. Melphalan 60 mg/m2 by vein on Days -3 and -2. Stem cell transplant on Day 0. Dexamethasone 8 mg by vein twice a day from Day -9 PM to Day -2 PM. Caphosol oral rinses 30 mL four times a day from Day -9 until discharge. Oral glutamine 15 g four times a day, swished, gargled and spit on Day -9 until discharge. Pyridoxine 100 mg by vein or mouth three times a day from Day -1.
干预措施: Palifermin (Drug)
Carfilzomib/SAHA + Gem/Bu/Mel + Auto Stem Cell Transplant SCT
Busulfan test dose of 32 mg/m2 by vein on Day -10 if inpatient, on Day -12 if outpatient, then AUC of 4,000 microMol.min on Days -8 to -5. Palifermin 60 microgram/kg by vein on Days -12 to -10 and Days 0, +1 and +2. SAHA 1,000 mg by mouth on Days -8 to -3. Gemcitabine loading dose of 75 mg/m2 followed by continuous infusion of the remaining dose of 1875 mg/m2 by vein on Days -8 and -3. Carfilzomib 27 mg/m2 by vein on Days -7 and -6, then on Days -2 and -1. SAHA 1,000 mg by mouth on Days -7 to -3. Melphalan 60 mg/m2 by vein on Days -3 and -2. Stem cell transplant on Day 0. Dexamethasone 8 mg by vein twice a day from Day -9 PM to Day -2 PM. Caphosol oral rinses 30 mL four times a day from Day -9 until discharge. Oral glutamine 15 g four times a day, swished, gargled and spit on Day -9 until discharge. Pyridoxine 100 mg by vein or mouth three times a day from Day -1.
干预措施: Dexamethasone (Drug)
Carfilzomib/SAHA + Gem/Bu/Mel + Auto Stem Cell Transplant SCT
Busulfan test dose of 32 mg/m2 by vein on Day -10 if inpatient, on Day -12 if outpatient, then AUC of 4,000 microMol.min on Days -8 to -5. Palifermin 60 microgram/kg by vein on Days -12 to -10 and Days 0, +1 and +2. SAHA 1,000 mg by mouth on Days -8 to -3. Gemcitabine loading dose of 75 mg/m2 followed by continuous infusion of the remaining dose of 1875 mg/m2 by vein on Days -8 and -3. Carfilzomib 27 mg/m2 by vein on Days -7 and -6, then on Days -2 and -1. SAHA 1,000 mg by mouth on Days -7 to -3. Melphalan 60 mg/m2 by vein on Days -3 and -2. Stem cell transplant on Day 0. Dexamethasone 8 mg by vein twice a day from Day -9 PM to Day -2 PM. Caphosol oral rinses 30 mL four times a day from Day -9 until discharge. Oral glutamine 15 g four times a day, swished, gargled and spit on Day -9 until discharge. Pyridoxine 100 mg by vein or mouth three times a day from Day -1.
干预措施: Caphosol (Drug)
Carfilzomib/SAHA + Gem/Bu/Mel + Auto Stem Cell Transplant SCT
Busulfan test dose of 32 mg/m2 by vein on Day -10 if inpatient, on Day -12 if outpatient, then AUC of 4,000 microMol.min on Days -8 to -5. Palifermin 60 microgram/kg by vein on Days -12 to -10 and Days 0, +1 and +2. SAHA 1,000 mg by mouth on Days -8 to -3. Gemcitabine loading dose of 75 mg/m2 followed by continuous infusion of the remaining dose of 1875 mg/m2 by vein on Days -8 and -3. Carfilzomib 27 mg/m2 by vein on Days -7 and -6, then on Days -2 and -1. SAHA 1,000 mg by mouth on Days -7 to -3. Melphalan 60 mg/m2 by vein on Days -3 and -2. Stem cell transplant on Day 0. Dexamethasone 8 mg by vein twice a day from Day -9 PM to Day -2 PM. Caphosol oral rinses 30 mL four times a day from Day -9 until discharge. Oral glutamine 15 g four times a day, swished, gargled and spit on Day -9 until discharge. Pyridoxine 100 mg by vein or mouth three times a day from Day -1.
干预措施: Glutamine (Drug)
Carfilzomib/SAHA + Gem/Bu/Mel + Auto Stem Cell Transplant SCT
Busulfan test dose of 32 mg/m2 by vein on Day -10 if inpatient, on Day -12 if outpatient, then AUC of 4,000 microMol.min on Days -8 to -5. Palifermin 60 microgram/kg by vein on Days -12 to -10 and Days 0, +1 and +2. SAHA 1,000 mg by mouth on Days -8 to -3. Gemcitabine loading dose of 75 mg/m2 followed by continuous infusion of the remaining dose of 1875 mg/m2 by vein on Days -8 and -3. Carfilzomib 27 mg/m2 by vein on Days -7 and -6, then on Days -2 and -1. SAHA 1,000 mg by mouth on Days -7 to -3. Melphalan 60 mg/m2 by vein on Days -3 and -2. Stem cell transplant on Day 0. Dexamethasone 8 mg by vein twice a day from Day -9 PM to Day -2 PM. Caphosol oral rinses 30 mL four times a day from Day -9 until discharge. Oral glutamine 15 g four times a day, swished, gargled and spit on Day -9 until discharge. Pyridoxine 100 mg by vein or mouth three times a day from Day -1.
干预措施: Pyridoxine (Drug)
结局指标
主要结局
Complete Remission (CR) Rate
时间窗: 100 days
Complete remission (CR) rate defined as percentage of number of complete responses in total number of patients treated.
次要结局
- Response Rates (RR)(100 days)