Study of CM4620 to Reduce the Severity of Pancreatitis Due to Asparaginase

Официальное название

CRSPA: Phase I/II Study of CM4620 to Reduce the Severity of Pancreatitis Due to Asparaginase

Обзор

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).

Подробное описание

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.

Вмешательства

• Препарат CM4620
  IV

Первичные конечные точки

• The number of CTCAE grade 3-5 events [Срок оценки: Within 28 days of receiving the medication]
• Responses to CM4620 [Срок оценки: 28-35 days after study entry.]

Вторичные конечные точки (4)

• Effect of CM4620 measured by levels of pancreatic enzymes [Срок оценки: 72 hours after study entry]
• Effect of CM4620: Necrosis [Срок оценки: 28-35 days from study entry]
• Effect of CM4620: Pseudocyst [Срок оценки: 28-35 days from study entry]
• Effect of CM4620: Incidence of SIRS [Срок оценки: 48-72 hours after study entry]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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 CM4620.
• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 3 центра

• Novant Health Presbyterian Hemby Children's Hospital — Charlotte
• Cincinnati Children's Hospital Medical Center — Cincinnati
• St. Jude Children's Research Hospital — Memphis

Идентификаторы

NCT: NCT04195347 · CRSPA · NCI-2019-08205

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗