Treatment of Relapsed or Refractory Acute Lymphoblastic Leukemia (ALL) With CMC-544 (Inotuzumab Ozogamycin), With or Without Later Addition of Rituximab
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 90
- 试验地点
- 1
- 主要终点
- Number of Patients With Response
研究概览
简要总结
The goal of this clinical research study is to learn if CMC-544 given alone, and possibly given in combination with rituximab, can help to control the disease in patients with ALL. The safety of the study drug(s) will also be studied.
详细描述
Study Drugs:
CMC-544 is a monoclonal antibody (a substance that can locate and bind to cancer cells). It is designed to attach to C22, a molecule that is found on most cancer cells with ALL. This may cause the cancer cells to die.
Rituximab is a monoclonal antibody that is designed to attach to leukemia cells and activate a series of events that may cause the cancer cells to die.
Study Drug Administration:
If you are found to be eligible to take part in this study, you will receive CMC-544 by vein over about 60 minutes on Day 1 of each study "cycle" or over 60 minutes at a lowered dose on Days 1, 8 and 15 of each cycle, depending on when you joined the study. No matter what dosing schedule you are on, you will receive the same total dosage of CMC-544. Each study cycle is about 3-4 weeks.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 16 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •1. Previously treated ALL (including Burkitt's lymphoma and lymphoblastic lymphoma) in relapse or primary refractory. Patients in first relapse will be eligible regardless of the first remission duration. At least 10 patients in Salvage 1-2 will be treated to assess anti-ALL response more precisely.
- •2. Age 16 years or older. Pediatric patients (\<16 years old) will be allowed into the study after safety is established, that is at least 10 adult patients having received 1 or more cycles each.
- •3. Zubrod performance status 0-3.
- •4. Adequate liver function (bilirubin \/= 1 year postmenopausal or surgically sterilized).
排除标准
- •Patient with active heart disease (NYHA class >/= 3 as assessed by history and physical examination).
- •Patients with a cardiac ejection fraction (as measured by either Radionuclide angiography (MUGA) or echocardiogram) < 45% are excluded.
- •Patients who receive other chemotherapy. Patients must have been off previous therapy for >/= 2 weeks and must have recovered from acute toxicity (to grade 1 or less) of all previous therapy prior to enrollment (consent signing). (Concurrent therapy for central nervous system [CNS] prophylaxis or treatment for CNS relapse is permitted). Treatment may start earlier if necessitated by the patient's medical condition (e.g. rapidly progressive disease) following discussion with the Principal Investigator.
- •Prior allogeneic stem cell transplant in previous 4 months.
- •Peripheral lymphoblasts > 50 x 10^9/L.
- •Pregnant and breast-feeding patients are excluded.
- •Patients with known hepatitis B are excluded.
研究组 & 干预措施
Period 1: CMC-544 (Inotuzumab Ozogamycin) 1.3mg/m^2
First patients > 16 years and < 16 years receive CMC-544 (Inotuzumab Ozogamycin) at a dose of 1.3 mg/m^2 by vein (IV) over 1 hour during Course 1, and 1.8 mg/m^2 IV over 1 hour during Course 2 and subsequently. In all other patients beginning dose of 1.8 mg/m^2 IV over 1 hour every 4 week cycle. With no improvement after 2 courses of CMC-544, addition of Rituximab dose 375 mg/m^2 IV (by vein) over 2-6 hours every 3-4 weeks.
干预措施: CMC-544 (Inotuzumab Ozogamycin) (Drug)
Period 3: Weekly CMC-544 (Inotuzumab Ozogamycin)
CMC-544 (Inotuzumab Ozogamycin) 0.8 mg/m^2 IV over 1 hour (+ 15 minutes) on Day 1, 0.5 mg/m^2 IV over 1 hour (+ 15 minutes) on Day 8, and 0.5 mg/m^2 IV over 1 hour (+ 15 minutes) on Day 15. Weekly doses can be given at + 1 day. Course may be repeated every 3 weeks. Rituximab will be given on Day 1 and CMC-544 on Day 2 of the first dose; with subsequent weekly doses, both will be given weekly, rituximab preceding CMC-544. The weekly dose of rituximab will be 375 mg/m2.
干预措施: CMC-544 (Inotuzumab Ozogamycin) (Drug)
Period 2: CMC-544 (Inotuzumab Ozogamycin) 1.8mg/m^2
First patients > 16 years and < 16 years receive CMC-544 (Inotuzumab Ozogamycin) at a dose of 1.3 mg/m^2 by vein (IV) over 1 hour during Course 1, and 1.8 mg/m^2 IV over 1 hour during Course 2 and subsequently. In all other patients beginning dose of 1.8 mg/m^2 IV over 1 hour every 4 week cycle. With no improvement after 2 courses of CMC-544, addition of Rituximab dose 375 mg/m^2 IV (by vein) over 2-6 hours every 3-4 weeks.
干预措施: CMC-544 (Inotuzumab Ozogamycin) (Drug)
Period 1: CMC-544 (Inotuzumab Ozogamycin) 1.3mg/m^2
First patients > 16 years and < 16 years receive CMC-544 (Inotuzumab Ozogamycin) at a dose of 1.3 mg/m^2 by vein (IV) over 1 hour during Course 1, and 1.8 mg/m^2 IV over 1 hour during Course 2 and subsequently. In all other patients beginning dose of 1.8 mg/m^2 IV over 1 hour every 4 week cycle. With no improvement after 2 courses of CMC-544, addition of Rituximab dose 375 mg/m^2 IV (by vein) over 2-6 hours every 3-4 weeks.
干预措施: Rituximab (Drug)
Period 2: CMC-544 (Inotuzumab Ozogamycin) 1.8mg/m^2
First patients > 16 years and < 16 years receive CMC-544 (Inotuzumab Ozogamycin) at a dose of 1.3 mg/m^2 by vein (IV) over 1 hour during Course 1, and 1.8 mg/m^2 IV over 1 hour during Course 2 and subsequently. In all other patients beginning dose of 1.8 mg/m^2 IV over 1 hour every 4 week cycle. With no improvement after 2 courses of CMC-544, addition of Rituximab dose 375 mg/m^2 IV (by vein) over 2-6 hours every 3-4 weeks.
干预措施: Rituximab (Drug)
Period 3: Weekly CMC-544 (Inotuzumab Ozogamycin)
CMC-544 (Inotuzumab Ozogamycin) 0.8 mg/m^2 IV over 1 hour (+ 15 minutes) on Day 1, 0.5 mg/m^2 IV over 1 hour (+ 15 minutes) on Day 8, and 0.5 mg/m^2 IV over 1 hour (+ 15 minutes) on Day 15. Weekly doses can be given at + 1 day. Course may be repeated every 3 weeks. Rituximab will be given on Day 1 and CMC-544 on Day 2 of the first dose; with subsequent weekly doses, both will be given weekly, rituximab preceding CMC-544. The weekly dose of rituximab will be 375 mg/m2.
干预措施: Rituximab (Drug)
结局指标
主要结局
Number of Patients With Response
时间窗: After cycle 2, for up to 8 cycles
Primary endpoint for efficacy is response which is defined as: Complete Remission (CR), Complete Remission without recovery of counts (CRi) or Partial Remission (PR). Complete remission (CR): Disappearance of all clinical and/or radiologic evidence of disease. Neutrophil count \> 1.0 x109/L, platelet count \>100x109/L, and normal marrow differential (\< 5% blasts). 8.2 Complete remission without recovery of counts (CRi): Peripheral blood and marrow results as for CR, but with incomplete recover of counts (platelets \< 100 x 109/L; neutrophils \< 1 x 109/L). Partial remission (PR): Peripheral blood count recovery as for CR, but with decrease in marrow blasts of \> 50% and not more than 25% abnormal cells in the marrow.
次要结局
未报告次要终点