CRSPA: Phase I/II Study of CM4620 to Reduce the Severity of Pancreatitis Due to Asparaginase
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 42
- 试验地点
- 3
- 主要终点
- Responses to CM4620
研究概览
简要总结
This is a phase I/II clinical trial assessing the tolerability and efficacy of CM4620 in children and young adults with acute pancreatitis caused by asparaginase. The tolerability of CM4620 when given to patients receiving frontline chemotherapy will be determined. The effectiveness in reducing the severity of pancreatitis will be estimated.
Primary Objectives
To assess the safety of CM4620 administration in children and young adults with asparaginase associated pancreatitis (AAP).
To profile dose-limiting toxicities and responses of the patients treated in the dose-finding phase.
To estimate the efficacy of CM4620 to prevent pseudocyst or necrotizing pancreatitis in children with AAP.
Secondary Objectives
To determine the effect of CM4620 on the incidence of severe pancreatitis
To determine the effect of CM4620 on the incidence of Systemic Inflammatory Response Syndrome (SIRS).
详细描述
This is an open label safety and efficacy evaluation with comparison of toxicity to a historical control population (TOTXVI). There will be 3 cohorts of patients enrolled, and the dose for each cohort will be determined based on the toxicities experienced in the ongoing and prior cohorts.
An initial 9 patients (cohort 1) will be enrolled and will receive dose level 1 and monitored for toxicity. If the therapy is well tolerated, 6 patients (cohort 2) will be treated at dose level 2. Subsequent enrollment of 9 patients (cohort 3) will be at either dose level 1 or 2 based on tolerability. The keyboard design will be used to determine the dosing for cohorts 2 and 3. Additional patients will be enrolled at the recommended phase II dose (RP2D) until a total of 24 patients have been treated at that dose, including any treated during the dose-finding phase.
CM4620 will be given days 1-4 as an IV infusion beginning within 36 hours of the onset of acute pancreatitis associated abdominal pain and within 8 hours of enrollment. For patients with prior abdominal pain or in those unable to communicate the location/characteristic of their pain, a change in the characteristic of the pain or new enzyme elevation/imaging findings after previously normal studies will determine the timing of onset of pancreatitis.
Patients will be followed for about 4 months after treatment.
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
- — 至 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Acute pancreatitis with elevation of amylase OR lipase ≥ 3x the upper limit of normal AND at least 1 of: abdominal pain consistent with acute pancreatitis OR imaging findings consistent with acute pancreatitis.
- •Receipt of any form of asparaginase within the prior 49 days.
- •Patient with acute lymphoblastic leukemia/ lymphoma age < 22 years receiving therapy with curative intent.
排除标准
- •Prior episode of pancreatitis.
- •QTc at baseline > 450 msec.
- •Creatinine > 3x the upper limit of normal for age or total bilirubin >3x the upper limit for normal for age without evidence of leukemic infiltrate or hemolysis.
- •Receipt of another investigational agent within the prior 7 days.
- •History of allergy to eggs or known hypersensitivity to any component of CM
- •Positive pregnancy test or breastfeeding. Females of childbearing potential must have a negative urine or serum pregnancy test prior to enrollment. Males and females of childbearing potential must agree to use effective contraception for at least twelve months following the completion of therapy.
- •Inability or unwillingness of research participant or legal guardian/representative to give written informed consent.
研究组 & 干预措施
CM4620 Treatment
Phase I:
Cohort 1 patients receive CM4620 IV at dose level 1 on days 1-4. Cohort 2 patients receive CM4620 IV at dose level 2 on days 1-4. Cohort 3 patients receive CM4620 IV at either dose level 1 or 2 on days 1-4
Phase II:
Patients will receive CM4620 IV on days 1-4 at the recommended Phase II dose (RP2D) as determined in Phase I.
干预措施: CM4620 (Drug)
结局指标
主要结局
Responses to CM4620
时间窗: 28-35 days after study entry.
We will evaluate the rate of pancreatic necrosis or pseudocyst formation using radiographic imaging
The number of CTCAE grade 3-5 events
时间窗: Within 28 days of receiving the medication
Drug safety measuring the number of CTCAE grade 3-5 events
次要结局
- Effect of CM4620: Necrosis(28-35 days from study entry)
- Effect of CM4620: Pseudocyst(28-35 days from study entry)
- Effect of CM4620 measured by levels of pancreatic enzymes(72 hours after study entry)
- Effect of CM4620: Incidence of SIRS(48-72 hours after study entry)