Phase I/II Study of Moxetumomab Pasudotox in Patients With Relapsed and/or Refractory Acute Lymphoblastic Leukemia (ALL)
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- Maximum Tolerated Dose (MTD) of Moxetumomab
研究概览
简要总结
The goal of this clinical research study is to find the highest tolerable dose of moxetumomab pasudotox that can be given to patients with relapsed and/or refractory ALL.
详细描述
Study Groups:
If you are found to be eligible to take part in this study, you will be assigned to a study group based on when you join this study. Up to 4 groups of 3-6 participants will be enrolled in the Phase 1 portion of the study.
If you are in Phase 1, the dose of moxetumomab pasudotox you receive will depend on when you join the study. The first group will receive the lowest dose level of moxetumomab pasudotox. Each additional group will receive a higher dose than the previous group, if no intolerable side effects were seen.
If you are in Phase 2, you will receive the highest dose of moxetumomab pasudotox found to be safe in the Phase 1 portion of the study.
Study Drug Administration:
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients age 18 years or older with previously treated ALL (relapsed and/or refractory after prior therapy); patients with relapsed/refractory biphenotypic leukemia expressing the appropriate antigen (CD22) are also eligible to participate, Pediatric patients younger than 18 may be considered with sponsor approval once the MTD has been established in the adult population.
- •Eastern Cooperative Oncology Group (ECOG) Performance status 0-
- •Adequate liver function (bilirubin less than or equal to 1.5 mg/dL and serum glutamate pyruvate transaminase (SGPT) or serum glutamate oxaloacetate transaminase (SGOT) less than or equal 2.5 x upper limit of normal (ULN), unless considered due to tumor or hemolysis), and renal function ( Calculated CrCl of greater than or equal to 50 or serum creatinine less than 2 x ULN.) Even if organ function abnormalities are considered due to tumor, the upper limit for bilirubin is less than or equal to 2.0 mg/dL (unless due to hemolysis or Gilbert's disease, i.e. mainly indirect bilirubin) and creatinine less than or equal 2 mg/dL
- •Provision of written informed consent.
排除标准
- •Patient with active heart disease (NYHA class greater than or equal to 2 as assessed by history and physical examination).
- •Patients with a cardiac ejection fraction (as measured by either multigated radionuclide angiography (MUGA) or echocardiogram) less than 40%
- •Patients with active hepatitis
- •Pregnant or breast-feeding women. Women of childbearing potential must have a negative urine or serum pregnancy test within 14 days of start of treatment.
- •prior radioimmunotherapy within 3 years of enrollment
- •serum albumin less than 2g/dL
- •oxygen saturation at rest by pulse oximetry less than 88% or PaO2 less than or equal to 55mm Hg
- •history of microangiopathic hemolysis, TTP or HUS.
- •symptomatic central nervous system (CNS) involvement
- •Less than 100 days post -transplant or any evidence of active graft-versus-host disease (GVHD)
- •systemic chemotherapy less than 14 days prior; however treatment may start earlier if there is evidence of rapidly progressive disease if approved by the Principal Investigator
- •monoclonal antibody therapy less than 1 month
- •investigational agents within 28 days of dosing; however treatment may start earlier if there is evidence of rapidly progressive disease if approved by the Principal Investigator
- •history of exposure to pseudomonas exotoxin containing molecule
- •Patients with active lung infection or active pulmonary edema.
- •Patients with laboratory findings consistent with Grade equal to greater than 3 disseminated intravascular coagulation (DIC) or any Grade 2 DIC that does not correct.
- •Patients with clinically significant ophthalmologic findings (as determined by an ophthalmologist) during screening should be excluded from the trial
- •Pre-treatment greater than corrected QT interval (QTc) interval of 490 ms
研究组 & 干预措施
Moxetumomab Pasudotox
Phase I Starting Dose: 30 µg/kg by vein every other day for 6 doses on Days 1, 3, 5, 7, 9, and 11 of each 21-day cycle.
Phase II Starting Dose: Maximum tolerated dose from Phase I.
干预措施: Moxetumomab Pasudotox (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD) of Moxetumomab
时间窗: After second 21 day cycle
Maximum tolerated dose defined as the highest dose level in which 6 patients have been evaluated for toxicity and fewer than 2 dose limiting toxicities (DLTs) were observed. A non-hematologic DLT defined as a clinically significant Grade 3 or 4 adverse event or abnormal laboratory value assessed by treating physician as related to study drug (and unrelated to disease progression, intercurrent illness, or concomitant medications) occurring during the first 21(+/- 2) days on study. A hematologic dose-limiting toxicity defined as severe myelosuppression with a hypoplastic marrow with less than 5% cellularity and no evidence of leukemia 42 days from start of therapy.
次要结局
- Overall Response Rate(After second 21 day cycle)