An Open-Label, Multicenter Study of Recombinant Crisantaspase Produced in Pseudomonas Fluorescens (RC-P) in Patients With Acute Lymphoblastic Leukemia (ALL)/Lymphoblastic Lymphoma (LBL) Following Hypersensitivity to E. Coli-derived Asparaginases
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 229
- 试验地点
- 74
- 主要终点
- Response Rate During the First Course of JZP-458 Administration
研究概览
简要总结
This is an open-label, multicenter, dose confirmation, and PK study of JZP-458 in patients (of any age) with ALL/LBL who are hypersensitive to E. coli-derived asparaginases (allergic reaction or silent inactivation). This study is designed to assess the tolerability and efficacy of JZP-458 (only in patients who develop hypersensitivity to an E. coli-derived asparaginase), as measured by asparaginase activity.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Pediatric and adult patients with a diagnosis of ALL or LBL.
- •Have had an allergic reaction to a long-acting E. coli-derived asparaginase OR have silent inactivation.
- •Have 1 or more courses of E. coli-derived asparaginase remaining in his/her treatment plan.
- •Patients must have, in the opinion of the Investigator, fully recovered from their prior allergic reaction to E. coli-derived asparaginase.
排除标准
- •Have previously received asparaginase Erwinia chrysanthemi or JZP-
- •Have relapsed ALL or LBL.
- •Are concurrently receiving another investigational agent and/or treated with an investigational device at the same time as JZP-458 (within 48 hours) during Course 1 of JZP-
- •Have a history of ≥ Grade 3 pancreatitis.
- •Prior history of asparaginase-associated ≥ Grade 3 hemorrhagic event or asparaginase-associated thrombus requiring anticoagulation therapy, excluding catheter-related thrombotic events.
研究组 & 干预措施
JZP-458
Part A (IM JZP-458) of the study will have 2 IM cohorts:
- Cohort 1: a JZP-458 repeat dose/confirmatory cohort; a final IM JZP-458 dose level will be selected, and
- Cohort 2: an expansion cohort to confirm the efficacy and safety of the final IM JZP-458 dose level and schedule
Part B (IV JZP-458 Dose Confirmation) will be conducted to define the optimal dose of the IV administration of JZP-458 for further study in ALL/LBL patients as a repeated dose.
Additional courses of JZP-458 (IM or IV depending on patient's allocation at study enrollment) will be administered based on each patient's original treatment plan for as long as the patient derives clinical benefit.
干预措施: IM JZP-458 (Drug)
JZP-458
Part A (IM JZP-458) of the study will have 2 IM cohorts:
- Cohort 1: a JZP-458 repeat dose/confirmatory cohort; a final IM JZP-458 dose level will be selected, and
- Cohort 2: an expansion cohort to confirm the efficacy and safety of the final IM JZP-458 dose level and schedule
Part B (IV JZP-458 Dose Confirmation) will be conducted to define the optimal dose of the IV administration of JZP-458 for further study in ALL/LBL patients as a repeated dose.
Additional courses of JZP-458 (IM or IV depending on patient's allocation at study enrollment) will be administered based on each patient's original treatment plan for as long as the patient derives clinical benefit.
干预措施: IV JZP-458 (Drug)
结局指标
主要结局
Response Rate During the First Course of JZP-458 Administration
时间窗: Baseline up to 2 weeks
The response rate was defined as the number (proportion) of patients with the last 72-hour nadir serum asparaginase activity (NSAA) level ≥ 0.1 IU/mL during the first course of IM JZP-458. Blood samples were collected for serum asparaginase activity level determination.
Number of Participants With Any Treatment-emergent Adverse Events (TEAEs)
时间窗: Date of written informed consent up to 30 days after last dose of last course, up to approximately 2 years 7 months
An adverse event (AE) is any untoward medical occurrence associated with the use of a drug in humans, whether or not considered related to study drug. AEs were classified by the Investigator using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 5.0.
次要结局
- Number of Participants With Last 48-hour NSAA Level ≥ 0.1 IU/mL During The First Course (6 Doses) of JZP-458 Administration(Baseline up to 2 weeks)
- Number of Participants With Last NSAA Levels ≥ 0.4 IU/mL During The First Course (6 Doses) of JZP-458 Administration(Baseline up to 2 weeks)
- Mean Serum Asparaginase Activity Levels in First Course of JZP-458 Administration(Up to 2 weeks (6 doses))
- Number of Participants Who Are Anti-drug Antibody Positive or Negative Against JZP-458(Baseline up to 30 days (ADA- samples) after last dose of last course and up to 6 months (ADA+ samples) after last dose of last course, up to approximately 2 years 7 months)