Hyper-CVAD With Liposomal Vincristine (Hyper-CMAD) in Acute Lymphoblastic Leukemia
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 31
- 试验地点
- 1
- 主要终点
- Number of Patients With Complete Remission at One Year
研究概览
简要总结
Any time the words "you," "your," "I," or "me" appear, it is meant to apply to the potential participant.
The goal of this clinical research study is to learn if intensive chemotherapy (hyper-CVAD therapy) given in combination with liposomal vincristine (Marqibo), in addition to rituximab for patients who are CD20 positive and/or imatinib, dasatinib, or ruxolitinib for patients with the Philadelphia (Ph) chromosome, can help to control ALL or lymphoblastic lymphoma. The safety of this treatment will also be studied. CD20 is a protein "marker" that is found in leukemia or lymphoma cells.
This is an investigational study. Liposomal vincristine is FDA approved for the treatment of patients with CLL who have relapsed at least 2 times. All of the other study drugs used in this study are FDA approved and commercially available. The combination of liposomal vincristine with the other study drugs is also being used in research only.
Up to 65 patients will take part in this study. All will be enrolled at MD Anderson.
详细描述
The Study Drugs:
Adriamycin (doxorubicin) is designed to stop the growth of cancer cells, which may cause the cells to die.
Cyclophosphamide is designed to disrupt with the multiplication of cancer cells, which may slow or stop their growth and spread throughout the body. This may cause the cancer cells to die.
Cytarabine (Ara-C) is designed to insert itself into DNA (the genetic material of cells) of cancer cells and stop the DNA from repairing itself.
Dexamethasone is a corticosteroid that is similar to a natural hormone made by your body.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- •Newly diagnosed previously untreated ALL or lymphoblastic lymphoma >/= 18 years old. Allow urgent administration of cytarabine/hydrea/atra prior to starting treatment on protocol. Allow previous administration of up to one course of Hyper-CVAD and/or FDA approved TKI.
- •Zubrod performance status </=
- •Adequate liver function (bilirubin </= 3.0 mg/dl unless considered due to tumor) and renal function (creatinine </= 3.0 mg/dl, unless considered due to tumor).
- •No active co-existing malignancy with life expectancy less than 12 months due to that malignancy.
- •All men and women of childbearing potential who are participating in the study must agree to use effective forms of birth control throughout the duration of their treatment.
- •Adequate cardiac function as assessed clinically
排除标准
- •Pregnant or lactating women. Women of childbearing potential (WOCB) must have a blood or urine pregnancy test within 7 days prior to administration of the study drug. (WOCB is defined as a woman who has not undergone hysterectomy or bilateral oophorectomy and has not been naturally postmenopausal for at least 24 consecutive months).
- •Active Grade III-IV cardiac failure as defined by the New York Heart Association criteria, uncontrolled angina or MI within 6 months.
- •Patients with medical conditions that compromise their ability to complete the study or confound interpretation of study results.
研究组 & 干预措施
Hyper-CMAD + Rituximab
Odd Courses 1, 3, 5, 7: Rituximab 375 mg/m2 IV Day 1 & 8 Courses 1 & 3; Imatinib oral 600 mg days 1-14 Course 1 then continuously; Cyclophosphamide 300 mg/m2 IV every; 12 hours for 6 doses; Mesna 600 mg/m2/day IV Days 1-3; Doxorubicin 50 mg/m2 IV CVC Day 4; VSLI 2.25 mg/M2 IV Day 1 & 8; Pegfilgrastim 6 mg/kg after chemotherapy + G-CSF 10 µg/kg/day; Dexamethasone 40 mg IV or P.O. daily days 1-4 and days 11-14 +/- 3 days.
干预措施: Doxorubicin (Drug)
Hyper-CMAD + Rituximab
Odd Courses 1, 3, 5, 7: Rituximab 375 mg/m2 IV Day 1 & 8 Courses 1 & 3; Imatinib oral 600 mg days 1-14 Course 1 then continuously; Cyclophosphamide 300 mg/m2 IV every; 12 hours for 6 doses; Mesna 600 mg/m2/day IV Days 1-3; Doxorubicin 50 mg/m2 IV CVC Day 4; VSLI 2.25 mg/M2 IV Day 1 & 8; Pegfilgrastim 6 mg/kg after chemotherapy + G-CSF 10 µg/kg/day; Dexamethasone 40 mg IV or P.O. daily days 1-4 and days 11-14 +/- 3 days.
干预措施: Rituximab (Drug)
Hyper-CMAD + Rituximab
Odd Courses 1, 3, 5, 7: Rituximab 375 mg/m2 IV Day 1 & 8 Courses 1 & 3; Imatinib oral 600 mg days 1-14 Course 1 then continuously; Cyclophosphamide 300 mg/m2 IV every; 12 hours for 6 doses; Mesna 600 mg/m2/day IV Days 1-3; Doxorubicin 50 mg/m2 IV CVC Day 4; VSLI 2.25 mg/M2 IV Day 1 & 8; Pegfilgrastim 6 mg/kg after chemotherapy + G-CSF 10 µg/kg/day; Dexamethasone 40 mg IV or P.O. daily days 1-4 and days 11-14 +/- 3 days.
干预措施: Imatinib (Drug)
Hyper-CMAD + Rituximab
Odd Courses 1, 3, 5, 7: Rituximab 375 mg/m2 IV Day 1 & 8 Courses 1 & 3; Imatinib oral 600 mg days 1-14 Course 1 then continuously; Cyclophosphamide 300 mg/m2 IV every; 12 hours for 6 doses; Mesna 600 mg/m2/day IV Days 1-3; Doxorubicin 50 mg/m2 IV CVC Day 4; VSLI 2.25 mg/M2 IV Day 1 & 8; Pegfilgrastim 6 mg/kg after chemotherapy + G-CSF 10 µg/kg/day; Dexamethasone 40 mg IV or P.O. daily days 1-4 and days 11-14 +/- 3 days.
干预措施: Cyclophosphamide (Drug)
Hyper-CMAD + Rituximab
Odd Courses 1, 3, 5, 7: Rituximab 375 mg/m2 IV Day 1 & 8 Courses 1 & 3; Imatinib oral 600 mg days 1-14 Course 1 then continuously; Cyclophosphamide 300 mg/m2 IV every; 12 hours for 6 doses; Mesna 600 mg/m2/day IV Days 1-3; Doxorubicin 50 mg/m2 IV CVC Day 4; VSLI 2.25 mg/M2 IV Day 1 & 8; Pegfilgrastim 6 mg/kg after chemotherapy + G-CSF 10 µg/kg/day; Dexamethasone 40 mg IV or P.O. daily days 1-4 and days 11-14 +/- 3 days.
干预措施: Mesna (Drug)
Hyper-CMAD + Rituximab
Odd Courses 1, 3, 5, 7: Rituximab 375 mg/m2 IV Day 1 & 8 Courses 1 & 3; Imatinib oral 600 mg days 1-14 Course 1 then continuously; Cyclophosphamide 300 mg/m2 IV every; 12 hours for 6 doses; Mesna 600 mg/m2/day IV Days 1-3; Doxorubicin 50 mg/m2 IV CVC Day 4; VSLI 2.25 mg/M2 IV Day 1 & 8; Pegfilgrastim 6 mg/kg after chemotherapy + G-CSF 10 µg/kg/day; Dexamethasone 40 mg IV or P.O. daily days 1-4 and days 11-14 +/- 3 days.
干预措施: VSLI (Drug)
Hyper-CMAD + Rituximab
Odd Courses 1, 3, 5, 7: Rituximab 375 mg/m2 IV Day 1 & 8 Courses 1 & 3; Imatinib oral 600 mg days 1-14 Course 1 then continuously; Cyclophosphamide 300 mg/m2 IV every; 12 hours for 6 doses; Mesna 600 mg/m2/day IV Days 1-3; Doxorubicin 50 mg/m2 IV CVC Day 4; VSLI 2.25 mg/M2 IV Day 1 & 8; Pegfilgrastim 6 mg/kg after chemotherapy + G-CSF 10 µg/kg/day; Dexamethasone 40 mg IV or P.O. daily days 1-4 and days 11-14 +/- 3 days.
干预措施: G-CSF (Drug)
Hyper-CMAD + Rituximab
Odd Courses 1, 3, 5, 7: Rituximab 375 mg/m2 IV Day 1 & 8 Courses 1 & 3; Imatinib oral 600 mg days 1-14 Course 1 then continuously; Cyclophosphamide 300 mg/m2 IV every; 12 hours for 6 doses; Mesna 600 mg/m2/day IV Days 1-3; Doxorubicin 50 mg/m2 IV CVC Day 4; VSLI 2.25 mg/M2 IV Day 1 & 8; Pegfilgrastim 6 mg/kg after chemotherapy + G-CSF 10 µg/kg/day; Dexamethasone 40 mg IV or P.O. daily days 1-4 and days 11-14 +/- 3 days.
干预措施: Pegfilgrastim (Drug)
Hyper-CMAD + Rituximab
Odd Courses 1, 3, 5, 7: Rituximab 375 mg/m2 IV Day 1 & 8 Courses 1 & 3; Imatinib oral 600 mg days 1-14 Course 1 then continuously; Cyclophosphamide 300 mg/m2 IV every; 12 hours for 6 doses; Mesna 600 mg/m2/day IV Days 1-3; Doxorubicin 50 mg/m2 IV CVC Day 4; VSLI 2.25 mg/M2 IV Day 1 & 8; Pegfilgrastim 6 mg/kg after chemotherapy + G-CSF 10 µg/kg/day; Dexamethasone 40 mg IV or P.O. daily days 1-4 and days 11-14 +/- 3 days.
干预措施: Dexamethasone (Drug)
Hyper-CMAD
Courses 2, 4, 6, 8: Rituximab 375 mg/m2 IV Day 1 & 8 Courses 2 & 4; Imatinib oral 600 mg; Methotrexate 200 mg/m2 IV over 2 hours followed by 8-0- mg/m2 over 22 hours on Day 1; Solu-Medrol 40 mg IV hours approximately every 12 hours +/- 2 hours for 6 doses days 1-3 +/- 3 days; Decadron 40 mg IV or orally 4 times Days 1-4; Ara-C 3 gm/m2 IV every 2 hours, 4 doses on Days 2-3; Pegfilgrastim 6 mg/kg after chemotherapy + G-CSF 10 mg/kg/day.
干预措施: Rituximab (Drug)
Hyper-CMAD
Courses 2, 4, 6, 8: Rituximab 375 mg/m2 IV Day 1 & 8 Courses 2 & 4; Imatinib oral 600 mg; Methotrexate 200 mg/m2 IV over 2 hours followed by 8-0- mg/m2 over 22 hours on Day 1; Solu-Medrol 40 mg IV hours approximately every 12 hours +/- 2 hours for 6 doses days 1-3 +/- 3 days; Decadron 40 mg IV or orally 4 times Days 1-4; Ara-C 3 gm/m2 IV every 2 hours, 4 doses on Days 2-3; Pegfilgrastim 6 mg/kg after chemotherapy + G-CSF 10 mg/kg/day.
干预措施: Imatinib (Drug)
Hyper-CMAD
Courses 2, 4, 6, 8: Rituximab 375 mg/m2 IV Day 1 & 8 Courses 2 & 4; Imatinib oral 600 mg; Methotrexate 200 mg/m2 IV over 2 hours followed by 8-0- mg/m2 over 22 hours on Day 1; Solu-Medrol 40 mg IV hours approximately every 12 hours +/- 2 hours for 6 doses days 1-3 +/- 3 days; Decadron 40 mg IV or orally 4 times Days 1-4; Ara-C 3 gm/m2 IV every 2 hours, 4 doses on Days 2-3; Pegfilgrastim 6 mg/kg after chemotherapy + G-CSF 10 mg/kg/day.
干预措施: VSLI (Drug)
Hyper-CMAD
Courses 2, 4, 6, 8: Rituximab 375 mg/m2 IV Day 1 & 8 Courses 2 & 4; Imatinib oral 600 mg; Methotrexate 200 mg/m2 IV over 2 hours followed by 8-0- mg/m2 over 22 hours on Day 1; Solu-Medrol 40 mg IV hours approximately every 12 hours +/- 2 hours for 6 doses days 1-3 +/- 3 days; Decadron 40 mg IV or orally 4 times Days 1-4; Ara-C 3 gm/m2 IV every 2 hours, 4 doses on Days 2-3; Pegfilgrastim 6 mg/kg after chemotherapy + G-CSF 10 mg/kg/day.
干预措施: Solu-Medrol (Drug)
Hyper-CMAD
Courses 2, 4, 6, 8: Rituximab 375 mg/m2 IV Day 1 & 8 Courses 2 & 4; Imatinib oral 600 mg; Methotrexate 200 mg/m2 IV over 2 hours followed by 8-0- mg/m2 over 22 hours on Day 1; Solu-Medrol 40 mg IV hours approximately every 12 hours +/- 2 hours for 6 doses days 1-3 +/- 3 days; Decadron 40 mg IV or orally 4 times Days 1-4; Ara-C 3 gm/m2 IV every 2 hours, 4 doses on Days 2-3; Pegfilgrastim 6 mg/kg after chemotherapy + G-CSF 10 mg/kg/day.
干预措施: Methotrexate (Drug)
Hyper-CMAD
Courses 2, 4, 6, 8: Rituximab 375 mg/m2 IV Day 1 & 8 Courses 2 & 4; Imatinib oral 600 mg; Methotrexate 200 mg/m2 IV over 2 hours followed by 8-0- mg/m2 over 22 hours on Day 1; Solu-Medrol 40 mg IV hours approximately every 12 hours +/- 2 hours for 6 doses days 1-3 +/- 3 days; Decadron 40 mg IV or orally 4 times Days 1-4; Ara-C 3 gm/m2 IV every 2 hours, 4 doses on Days 2-3; Pegfilgrastim 6 mg/kg after chemotherapy + G-CSF 10 mg/kg/day.
干预措施: Ara-C (Drug)
Hyper-CMAD
Courses 2, 4, 6, 8: Rituximab 375 mg/m2 IV Day 1 & 8 Courses 2 & 4; Imatinib oral 600 mg; Methotrexate 200 mg/m2 IV over 2 hours followed by 8-0- mg/m2 over 22 hours on Day 1; Solu-Medrol 40 mg IV hours approximately every 12 hours +/- 2 hours for 6 doses days 1-3 +/- 3 days; Decadron 40 mg IV or orally 4 times Days 1-4; Ara-C 3 gm/m2 IV every 2 hours, 4 doses on Days 2-3; Pegfilgrastim 6 mg/kg after chemotherapy + G-CSF 10 mg/kg/day.
干预措施: G-CSF (Drug)
Hyper-CMAD
Courses 2, 4, 6, 8: Rituximab 375 mg/m2 IV Day 1 & 8 Courses 2 & 4; Imatinib oral 600 mg; Methotrexate 200 mg/m2 IV over 2 hours followed by 8-0- mg/m2 over 22 hours on Day 1; Solu-Medrol 40 mg IV hours approximately every 12 hours +/- 2 hours for 6 doses days 1-3 +/- 3 days; Decadron 40 mg IV or orally 4 times Days 1-4; Ara-C 3 gm/m2 IV every 2 hours, 4 doses on Days 2-3; Pegfilgrastim 6 mg/kg after chemotherapy + G-CSF 10 mg/kg/day.
干预措施: Pegfilgrastim (Drug)
结局指标
主要结局
Number of Patients With Complete Remission at One Year
时间窗: 1 year
The complete remission (CR) is the total number of patients who are in CR at one year divided by the total number of patients who received at least one dose of HCVAD with liposomal vincristine. CR was defined as the presence of \</=5% blasts in the bone marrow, with \>1x10\^9/L neutrophils, \>100x10\^9/L platelets in the perpherial blood, and no extramedullary disease.
Overall Survival
时间窗: Up to 7 years, 8 months
Time from date of treatment start until date of death due to any cause or last Follow-up. Survival will be measured by the estimated median survival computed by Kaplan-Meier (K-M) analysis, which is the time point at which the cumulative survival drops below 50%, if present. If not present then the median Overall Survival is not reached and not available (NA) as there are an insufficient number of participants with events. In either case ranges are provided for observed survival intervals used in the K-M analysis.
Complete Response Duration
时间窗: Up to 7 years, 8 months
The complete remission (CR) is the total number of patients who are in CR at one year divided by the total number of patients who received at least one dose of HCVAD with liposomal vincristine. CR was defined as the presence of \</=5% blasts in the bone marrow, with \>1x10\^9/L neutrophils, \>100x10\^9/L platelets in the perpherial blood, and no extramedullary disease. Response date to loss of response or last follow up. Remission duration will be measured by the estimated median remission duration computed by Kaplan-Meier (K-M) analysis, which is the time point at which the cumulative remission duration drops below 50%, if present. If not present then median remission duration is not reached and not available (NA) as there are an insufficient number of participants with events. In either case ranges are provided for observed survival intervals used in the K-M analysis..
次要结局
未报告次要终点