SPARK-ALL: A Multi-center, Open-label, Single-arm Phase 2/3 Trial Evaluating the Safety and Pharmacokinetics of Calaspargase Pegol for Treatment of Adults Aged 22 To >65 Years With Newly-diagnosed Philadelphia-negative ALL.
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 42
- 试验地点
- 40
- 主要终点
- Adverse Events (AEs) (Part 2)
研究概览
简要总结
The purpose of this phase 2/3 study is to confirm the recommended doses and to evaluate the safety and pharmacodynamics of Calaspargase pegol for the treatment of adult patients with Philadelphia-negative Acute Lymphoblastic Leukemia.
详细描述
The study will be conducted in 2 parts. Part 1 is a dose confirmation run-in period. Part 2 will enroll the remaining participants at the dose as confirmed or recommended in Part 1.
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
- 22 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged ≥22 and <55 years with newly-diagnosed and cytologically confirmed and documented Philadelphia-negative B-cell or T-cell ALL by World Health Organization (WHO) classification (2016).
- •Eastern Cooperative Oncology Group performance status (ECOG PS) 0 to
- •No prior therapy for ALL such as chemotherapy and radiation therapy before signing the informed consent except for limited treatment (≤7 days) with corticosteroids or hydroxyurea and a single dose of intrathecal cytarabine.
排除标准
- •Patients with Philadelphia chromosome positive ALL, Burkitt's leukemia, mixed lineage/mixed phenotype acute leukemia, and acute undifferentiated leukemia per WHO classification (2016).
- •Patients with Down syndrome.
- •Patients with Hepatitis B (positive for HBs antigen), and Hepatitis C (HCV antibody) at inclusion
- •Participants known to be HIV-positive.
- •Known history of non-gallstone-related pancreatitis.
- •Known severe hepatic impairment (bilirubin >3 x upper limit of normal [ULN]; transaminases >10 times ULN.
- •Pre-existing history of hepatic veno-occlusive disease (VOD).
- •Age ≥ 55 years.
- •BMI > 35 kg/m2.
研究组 & 干预措施
Calaspargase pegol (S95015)
干预措施: Calaspargase pegol (S95015) (Drug)
结局指标
主要结局
Adverse Events (AEs) (Part 2)
时间窗: From signing the ICF through 30 days after the last dose of the study drug in Delayed Intensification phase.
Including Treatment-emergent adverse events (TEAEs), adverse events of special interest (AESI); laboratory tests; vital signs; serious adverse events (SAEs) and AEs. AEs recoded and evaluated throughout the study in accordance with NCI CTCAE criteria 5.0.
Adverse Events (AEs) (Part 1)
时间窗: From signing the ICF through 30 days after the Calaspargase pegol administration at Day 4 (or Day 5 or Day 6) in the Remission Induction phase.
Including Treatment-emergent adverse events (TEAEs), adverse events of special interests (AESI); laboratory tests; vital signs; serious adverse events (SAEs) and AE. AEs recoded and evaluated throughout the study in accordance with NCI CTCAE criteria 5.0.
Plasma Asparaginase Activity (PAA) level (Part 1)
时间窗: Days 4, 5, 6 (Remission Induction phase) for PAA samples. Days 11, 18, 25 (Remission Induction phase) for TDM samples.
Assessment of PAA in Part 1 is based on population modeling analysis.
Nadir Plasma Asparaginase Activity (NPAA) (Part 2)
时间窗: Day 64 (Remission Consolidation Phase).
NPAA level ≥0.1 U/mL 21 days after the Remission Consolidation Phase Day 43 dose.
次要结局
- Minimal residual disease (MRD) (Part 1 and 2)(End of remission induction phase (Day 29).)
- Complete remission (CR) (Part 1 and 2)(Day 29 remission induction therapy)
- Survival (Part 1 and 2)(Through study completion an average of 3 months.)
- PAA-derived Area Under the PAA-Time Curve From Time 0 to Day 21 (AUC 0-21) after the Remission Induction Phase Day 4 dose (Part 1 and 2).(Days 4, 5, 6 & 11, 18, 25 (Remission Induction); for PAA & TDM samples respectively.)
- Plasma Asparaginase Activity (PAA) level ≥0.025, ≥0.1, ≥0.2, or ≥0.4 U/mL at predefined time points during Remission Induction phase and post- Remission Induction phase, respectively (Part 2)(Days 4-5-6 & 11-18-25 (Remission Induction); Days 15-16-43-44 & 22-29-36-50-57-64 (Consolidation); Days 22-23 & 29-36-43 (Interim Maintenance); Days 4-5-43-44 & 11-18-25-50-57-64 (Delayed Intensification) for PAA & TDM samples respectively.)
- PAA-derived maximum concentration (Cmax) after the Remission Induction Phase Day 4 dose (Part 1 and 2).(Days 4, 5, 6 & 11, 18, 25 (Remission Induction); for PAA & TDM samples respectively.)
- Plasma Asparaginase Activity (PAA) level ≥0.1 U/mL at any time during Remission Induction phase and post- Remission Induction phase, respectively (Part 2)(Days 4-5-6 & 11-18-25 (Remission Induction); Days 15-16-43-44 & 22-29-36-50-57-64 (Consolidation); Days 22-23 & 29-36-43 (Interim Maintenance); Days 4-5,43-44 & 11-18-25-50-57-64 (Delayed Intensification) for PAA & TDM samples respectively.)
- Anti-drug (calaspargase pegol) antibody (ADA) development (Part 1 and 2)(D4, D18, D29 (Remission Induction Phase), D15, D43 (Remission Consolidation Phase), D22 (Interim Maintenance Phase), D4, D43 (Delayed Intensification Phase), Day 365 (±7) after the first dose, Day 30 after the last dose if discontinuation.)