Lenalidomide Combined With Vorinostat/Gemcitabine/Busulfan/Melphalan With Autologous Stem-Cell Transplantation in Diffuse Large B-Cell Lymphoma of the ABC Subtype
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 8
- 试验地点
- 1
- 主要终点
- Event-free Survival (EFS)
研究概览
简要总结
The goal of this clinical research study is to find the highest tolerable dose of lenalidomide that can be given in combination with vorinostat, gemcitabine, busulfan, and melphalan, with a stem cell transplant, and with or without rituximab. Researchers also want to learn about the safety and effectiveness of this combination.
详细描述
Central Venous Catheter:
Many of the drugs given in this study and the stem cell transplant will be given by vein through a central venous catheter (CVC). A CVC is a sterile flexible tube and needle that will be placed into a large vein while you are under local anesthesia. Blood samples will also be drawn through your CVC. The CVC will remain in your body during treatment. Your doctor will explain this procedure to you in more detail, and you will be required to sign a separate consent form.
Study Groups:
If you are found to be eligible to take part in this study, you will be assigned to a dose level of lenalidomide based on when you join this study. Up to 3 dose levels of lenalidomide will be tested. At least 2 participants will be enrolled at each dose level. The first group of participants will receive the lowest dose level. Each new group will receive a higher dose than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of lenalidomide is found.
All participants will receive the same dose level of vorinostat, gemcitabine, busulfan, rituximab, and melphalan. However, if the first group of participants have any bad side effects, the dose level of gemcitabine may be lowered for all other groups.
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
- 15 Years 至 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with ABC (determined by immunohistochemistry using the Hans algorithmI) DLBCL with primary refractory disease, relapse <12 months after initial therapy, secondary International Prognostic Index (IPI) >1, less than partial response to salvage treatment or exposure to >3 salvage regimens
- •Adequate renal function, as defined by an estimated serum creatinine clearance >/= 50 ml/min (MDRD method) and/or serum creatinine </= 1.8 mg/dL
- •Adequate hepatic function (SGOT and/or SGPT </= 3 x ULN; bilirubin and ALP </= 2 x ULN
- •Adequate pulmonary function with FEV1, FVC and DLCO (corrected for Hgb) >/= 50%
- •Adequate cardiac function with left ventricular ejection fraction >/= 40%. No uncontrolled arrhythmias or symptomatic cardiac disease
- •ECOG performance status <2
- •Negative Beta HCG in woman with child-bearing potential
- •All study participants must be registered into the mandatory Revlimid REMS program, and be willing and able to comply with the requirements of the REMS program.
- •Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the Revlimid REMS program.
排除标准
- •Grade >/= 3 non-hematologic toxicity from previous therapy that has not resolved to </= G1
- •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 receiving effective antiretroviral therapy with undetectable viral load and normal CD4 counts
- •Radiation therapy in the month prior to enrollment
- •History of arterial thromboembolic events in the past 3 months and of venous thromboembolic events in the past month
- •History of hypersensitivity of lenalidomide or thalidomide
研究组 & 干预措施
Lenalidomide + Vorinostat/Gem/Bu/Mel + AutoSCT
Vorinostat and lenalidomide administered orally at the same time within 1 hour before the daily dose of chemotherapy.
Gemcitabine administered as a loading dose of 75 mg/m2 followed by infusion on days -8 and -3.
Busulfan test dose administered as outpatient before admission, or as inpatient on day -10. The "test dose" of 32 mg/m2 based on actual body weight. Doses of days -6 and -5 subsequently adjusted to target an AUC of 4,000 microMol.min-1.
Melphalan administered at 60 mg/m2 on days -3 and -2.
Patients with CD20+ tumors receive rituximab 375 mg/m2 on day -9 in the AM as an inpatient.
Dexamethasone 8 mg by vein twice a day from day -8 to day -2. Caphosol oral rinses 30 mL four times a day used from day -8. Oral glutamine, 15 g four times a day, swished, gargled and swallowed started on day -8.
Pyridoxine 100 mg by vein or mouth three times a day from day -1. Enoxaparin 40 mg subcutaneously daily from admission until platelet count drops below 50,000/mm3.
干预措施: Lenalidomide (Drug)
Lenalidomide + Vorinostat/Gem/Bu/Mel + AutoSCT
Vorinostat and lenalidomide administered orally at the same time within 1 hour before the daily dose of chemotherapy.
Gemcitabine administered as a loading dose of 75 mg/m2 followed by infusion on days -8 and -3.
Busulfan test dose administered as outpatient before admission, or as inpatient on day -10. The "test dose" of 32 mg/m2 based on actual body weight. Doses of days -6 and -5 subsequently adjusted to target an AUC of 4,000 microMol.min-1.
Melphalan administered at 60 mg/m2 on days -3 and -2.
Patients with CD20+ tumors receive rituximab 375 mg/m2 on day -9 in the AM as an inpatient.
Dexamethasone 8 mg by vein twice a day from day -8 to day -2. Caphosol oral rinses 30 mL four times a day used from day -8. Oral glutamine, 15 g four times a day, swished, gargled and swallowed started on day -8.
Pyridoxine 100 mg by vein or mouth three times a day from day -1. Enoxaparin 40 mg subcutaneously daily from admission until platelet count drops below 50,000/mm3.
干预措施: Vorinostat (Drug)
Lenalidomide + Vorinostat/Gem/Bu/Mel + AutoSCT
Vorinostat and lenalidomide administered orally at the same time within 1 hour before the daily dose of chemotherapy.
Gemcitabine administered as a loading dose of 75 mg/m2 followed by infusion on days -8 and -3.
Busulfan test dose administered as outpatient before admission, or as inpatient on day -10. The "test dose" of 32 mg/m2 based on actual body weight. Doses of days -6 and -5 subsequently adjusted to target an AUC of 4,000 microMol.min-1.
Melphalan administered at 60 mg/m2 on days -3 and -2.
Patients with CD20+ tumors receive rituximab 375 mg/m2 on day -9 in the AM as an inpatient.
Dexamethasone 8 mg by vein twice a day from day -8 to day -2. Caphosol oral rinses 30 mL four times a day used from day -8. Oral glutamine, 15 g four times a day, swished, gargled and swallowed started on day -8.
Pyridoxine 100 mg by vein or mouth three times a day from day -1. Enoxaparin 40 mg subcutaneously daily from admission until platelet count drops below 50,000/mm3.
干预措施: Gemcitabine (Drug)
Lenalidomide + Vorinostat/Gem/Bu/Mel + AutoSCT
Vorinostat and lenalidomide administered orally at the same time within 1 hour before the daily dose of chemotherapy.
Gemcitabine administered as a loading dose of 75 mg/m2 followed by infusion on days -8 and -3.
Busulfan test dose administered as outpatient before admission, or as inpatient on day -10. The "test dose" of 32 mg/m2 based on actual body weight. Doses of days -6 and -5 subsequently adjusted to target an AUC of 4,000 microMol.min-1.
Melphalan administered at 60 mg/m2 on days -3 and -2.
Patients with CD20+ tumors receive rituximab 375 mg/m2 on day -9 in the AM as an inpatient.
Dexamethasone 8 mg by vein twice a day from day -8 to day -2. Caphosol oral rinses 30 mL four times a day used from day -8. Oral glutamine, 15 g four times a day, swished, gargled and swallowed started on day -8.
Pyridoxine 100 mg by vein or mouth three times a day from day -1. Enoxaparin 40 mg subcutaneously daily from admission until platelet count drops below 50,000/mm3.
干预措施: Busulfan (Drug)
Lenalidomide + Vorinostat/Gem/Bu/Mel + AutoSCT
Vorinostat and lenalidomide administered orally at the same time within 1 hour before the daily dose of chemotherapy.
Gemcitabine administered as a loading dose of 75 mg/m2 followed by infusion on days -8 and -3.
Busulfan test dose administered as outpatient before admission, or as inpatient on day -10. The "test dose" of 32 mg/m2 based on actual body weight. Doses of days -6 and -5 subsequently adjusted to target an AUC of 4,000 microMol.min-1.
Melphalan administered at 60 mg/m2 on days -3 and -2.
Patients with CD20+ tumors receive rituximab 375 mg/m2 on day -9 in the AM as an inpatient.
Dexamethasone 8 mg by vein twice a day from day -8 to day -2. Caphosol oral rinses 30 mL four times a day used from day -8. Oral glutamine, 15 g four times a day, swished, gargled and swallowed started on day -8.
Pyridoxine 100 mg by vein or mouth three times a day from day -1. Enoxaparin 40 mg subcutaneously daily from admission until platelet count drops below 50,000/mm3.
干预措施: Melphalan (Drug)
Lenalidomide + Vorinostat/Gem/Bu/Mel + AutoSCT
Vorinostat and lenalidomide administered orally at the same time within 1 hour before the daily dose of chemotherapy.
Gemcitabine administered as a loading dose of 75 mg/m2 followed by infusion on days -8 and -3.
Busulfan test dose administered as outpatient before admission, or as inpatient on day -10. The "test dose" of 32 mg/m2 based on actual body weight. Doses of days -6 and -5 subsequently adjusted to target an AUC of 4,000 microMol.min-1.
Melphalan administered at 60 mg/m2 on days -3 and -2.
Patients with CD20+ tumors receive rituximab 375 mg/m2 on day -9 in the AM as an inpatient.
Dexamethasone 8 mg by vein twice a day from day -8 to day -2. Caphosol oral rinses 30 mL four times a day used from day -8. Oral glutamine, 15 g four times a day, swished, gargled and swallowed started on day -8.
Pyridoxine 100 mg by vein or mouth three times a day from day -1. Enoxaparin 40 mg subcutaneously daily from admission until platelet count drops below 50,000/mm3.
干预措施: Rituximab (Drug)
Lenalidomide + Vorinostat/Gem/Bu/Mel + AutoSCT
Vorinostat and lenalidomide administered orally at the same time within 1 hour before the daily dose of chemotherapy.
Gemcitabine administered as a loading dose of 75 mg/m2 followed by infusion on days -8 and -3.
Busulfan test dose administered as outpatient before admission, or as inpatient on day -10. The "test dose" of 32 mg/m2 based on actual body weight. Doses of days -6 and -5 subsequently adjusted to target an AUC of 4,000 microMol.min-1.
Melphalan administered at 60 mg/m2 on days -3 and -2.
Patients with CD20+ tumors receive rituximab 375 mg/m2 on day -9 in the AM as an inpatient.
Dexamethasone 8 mg by vein twice a day from day -8 to day -2. Caphosol oral rinses 30 mL four times a day used from day -8. Oral glutamine, 15 g four times a day, swished, gargled and swallowed started on day -8.
Pyridoxine 100 mg by vein or mouth three times a day from day -1. Enoxaparin 40 mg subcutaneously daily from admission until platelet count drops below 50,000/mm3.
干预措施: Dexamethasone (Drug)
Lenalidomide + Vorinostat/Gem/Bu/Mel + AutoSCT
Vorinostat and lenalidomide administered orally at the same time within 1 hour before the daily dose of chemotherapy.
Gemcitabine administered as a loading dose of 75 mg/m2 followed by infusion on days -8 and -3.
Busulfan test dose administered as outpatient before admission, or as inpatient on day -10. The "test dose" of 32 mg/m2 based on actual body weight. Doses of days -6 and -5 subsequently adjusted to target an AUC of 4,000 microMol.min-1.
Melphalan administered at 60 mg/m2 on days -3 and -2.
Patients with CD20+ tumors receive rituximab 375 mg/m2 on day -9 in the AM as an inpatient.
Dexamethasone 8 mg by vein twice a day from day -8 to day -2. Caphosol oral rinses 30 mL four times a day used from day -8. Oral glutamine, 15 g four times a day, swished, gargled and swallowed started on day -8.
Pyridoxine 100 mg by vein or mouth three times a day from day -1. Enoxaparin 40 mg subcutaneously daily from admission until platelet count drops below 50,000/mm3.
干预措施: Caphosol (Drug)
Lenalidomide + Vorinostat/Gem/Bu/Mel + AutoSCT
Vorinostat and lenalidomide administered orally at the same time within 1 hour before the daily dose of chemotherapy.
Gemcitabine administered as a loading dose of 75 mg/m2 followed by infusion on days -8 and -3.
Busulfan test dose administered as outpatient before admission, or as inpatient on day -10. The "test dose" of 32 mg/m2 based on actual body weight. Doses of days -6 and -5 subsequently adjusted to target an AUC of 4,000 microMol.min-1.
Melphalan administered at 60 mg/m2 on days -3 and -2.
Patients with CD20+ tumors receive rituximab 375 mg/m2 on day -9 in the AM as an inpatient.
Dexamethasone 8 mg by vein twice a day from day -8 to day -2. Caphosol oral rinses 30 mL four times a day used from day -8. Oral glutamine, 15 g four times a day, swished, gargled and swallowed started on day -8.
Pyridoxine 100 mg by vein or mouth three times a day from day -1. Enoxaparin 40 mg subcutaneously daily from admission until platelet count drops below 50,000/mm3.
干预措施: Glutamine (Drug)
Lenalidomide + Vorinostat/Gem/Bu/Mel + AutoSCT
Vorinostat and lenalidomide administered orally at the same time within 1 hour before the daily dose of chemotherapy.
Gemcitabine administered as a loading dose of 75 mg/m2 followed by infusion on days -8 and -3.
Busulfan test dose administered as outpatient before admission, or as inpatient on day -10. The "test dose" of 32 mg/m2 based on actual body weight. Doses of days -6 and -5 subsequently adjusted to target an AUC of 4,000 microMol.min-1.
Melphalan administered at 60 mg/m2 on days -3 and -2.
Patients with CD20+ tumors receive rituximab 375 mg/m2 on day -9 in the AM as an inpatient.
Dexamethasone 8 mg by vein twice a day from day -8 to day -2. Caphosol oral rinses 30 mL four times a day used from day -8. Oral glutamine, 15 g four times a day, swished, gargled and swallowed started on day -8.
Pyridoxine 100 mg by vein or mouth three times a day from day -1. Enoxaparin 40 mg subcutaneously daily from admission until platelet count drops below 50,000/mm3.
干预措施: Pyridoxine (Drug)
Lenalidomide + Vorinostat/Gem/Bu/Mel + AutoSCT
Vorinostat and lenalidomide administered orally at the same time within 1 hour before the daily dose of chemotherapy.
Gemcitabine administered as a loading dose of 75 mg/m2 followed by infusion on days -8 and -3.
Busulfan test dose administered as outpatient before admission, or as inpatient on day -10. The "test dose" of 32 mg/m2 based on actual body weight. Doses of days -6 and -5 subsequently adjusted to target an AUC of 4,000 microMol.min-1.
Melphalan administered at 60 mg/m2 on days -3 and -2.
Patients with CD20+ tumors receive rituximab 375 mg/m2 on day -9 in the AM as an inpatient.
Dexamethasone 8 mg by vein twice a day from day -8 to day -2. Caphosol oral rinses 30 mL four times a day used from day -8. Oral glutamine, 15 g four times a day, swished, gargled and swallowed started on day -8.
Pyridoxine 100 mg by vein or mouth three times a day from day -1. Enoxaparin 40 mg subcutaneously daily from admission until platelet count drops below 50,000/mm3.
干预措施: Enoxaparin (Drug)
Lenalidomide + Vorinostat/Gem/Bu/Mel + AutoSCT
Vorinostat and lenalidomide administered orally at the same time within 1 hour before the daily dose of chemotherapy.
Gemcitabine administered as a loading dose of 75 mg/m2 followed by infusion on days -8 and -3.
Busulfan test dose administered as outpatient before admission, or as inpatient on day -10. The "test dose" of 32 mg/m2 based on actual body weight. Doses of days -6 and -5 subsequently adjusted to target an AUC of 4,000 microMol.min-1.
Melphalan administered at 60 mg/m2 on days -3 and -2.
Patients with CD20+ tumors receive rituximab 375 mg/m2 on day -9 in the AM as an inpatient.
Dexamethasone 8 mg by vein twice a day from day -8 to day -2. Caphosol oral rinses 30 mL four times a day used from day -8. Oral glutamine, 15 g four times a day, swished, gargled and swallowed started on day -8.
Pyridoxine 100 mg by vein or mouth three times a day from day -1. Enoxaparin 40 mg subcutaneously daily from admission until platelet count drops below 50,000/mm3.
干预措施: Stem Cell Transplant (Procedure)
Lenalidomide + Vorinostat/Gem/Bu/Mel + AutoSCT
Vorinostat and lenalidomide administered orally at the same time within 1 hour before the daily dose of chemotherapy.
Gemcitabine administered as a loading dose of 75 mg/m2 followed by infusion on days -8 and -3.
Busulfan test dose administered as outpatient before admission, or as inpatient on day -10. The "test dose" of 32 mg/m2 based on actual body weight. Doses of days -6 and -5 subsequently adjusted to target an AUC of 4,000 microMol.min-1.
Melphalan administered at 60 mg/m2 on days -3 and -2.
Patients with CD20+ tumors receive rituximab 375 mg/m2 on day -9 in the AM as an inpatient.
Dexamethasone 8 mg by vein twice a day from day -8 to day -2. Caphosol oral rinses 30 mL four times a day used from day -8. Oral glutamine, 15 g four times a day, swished, gargled and swallowed started on day -8.
Pyridoxine 100 mg by vein or mouth three times a day from day -1. Enoxaparin 40 mg subcutaneously daily from admission until platelet count drops below 50,000/mm3.
干预措施: Palifermin (Drug)
结局指标
主要结局
Event-free Survival (EFS)
时间窗: Up to 2 years post transplant
Determined the 2-year event-free survival (EFS)
Maximum Tolerated Dose (MTD)
时间窗: Enrollment up to day 30 post transplant for each dosing cohort
Established the maximum tolerated dose (MTD) of lenalidomide combined with vorinostat/gemcitabine/busulfan/melphalan with autologous stem-cell transplant ASCT). Maximum tolerated dose (MTD) of lenalidomide based on DLT was defined as any Grade 4 or 5 nonhematologic, noninfectious toxicity or any grade 3 mucositis or skin toxicity lasting \> 5 days at their peak severity. Lenalidomide doses were chosen adaptively for successive cohorts with a minimum size of 2 patients. Toxicity scoring followed the National Cancer Institute Common Toxicity Criteria, version 4.
次要结局
- Toxicity Profile(Up to 2 years post transplant)
- Overall Survival (OS)(Up to 2 years post transplant)
- Complete Remission (CR) Rate(Up to 2 years post transplant)
- Pharmacodynamic Studies(Up to 2 years post transplant)
- Overall Remission Rate (ORR)(Up to 2 years post transplant)