A Pilot Study of Intravenous EZN-2285 (SC-PEG E. Coli L-asparaginase) or Intravenous Oncaspar® in the Treatment of Patients With High-Risk Acute Lymphoblastic Leukemia (ALL)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 166
- 试验地点
- 27
- 主要终点
- Pharmacokinetics (PK) (Half-life of SC-PEG E. Coli L-asparaginase (EZN-2285) Compared to Pegaspargase During Induction and Consolidation Therapy)
研究概览
简要总结
This randomized clinical trial is studying giving calaspargase pegol together with combination chemotherapy to see how well it works compared with giving pegaspargase together with combination chemotherapy in treating younger patients with newly diagnosed high-risk acute lymphoblastic leukemia. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells.
详细描述
PRIMARY OBJECTIVES:
I. To determine the pharmacokinetic comparability of EZN-2285 (calaspargase pegol) compared to Oncaspar (pegaspargase) given intravenously during induction and consolidation in patients with high-risk ALL receiving augmented Berlin-Frankfurt-Munster (BFM) therapy.
SECONDARY OBJECTIVES:
I. To describe the pharmacodynamics (PD) of EZN-2285 compared to Oncaspar given intravenously during induction and consolidation in patients with high-risk ALL receiving augmented BFM therapy.
II. To determine end of induction therapy day 29 minimal residual disease (MRD) for patients randomized to the EZN-2285 containing regimen compared to the Oncaspar® containing regimen.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 2 Years 至 30 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must be eligible for and enrolled on AALL08B1 or the successor classification study
- •Patients must have newly diagnosed high-risk B lymphoblastic leukemia (World Health Organization [WHO] 2008 classification) (also termed B-precursor acute lymphoblastic leukemia)
- •White blood cell (WBC) >= 50,000/μL for patients age 1-9 OR any WBC count for patients age 10-30 or for patients treated with prior steroids
- •Patients shall have had no prior cytotoxic chemotherapy with the exception of steroids and intrathecal cytarabine; intrathecal chemotherapy with cytarabine is allowed prior to registration for patient convenience; this is usually done at the time of the diagnostic bone marrow or venous line placement to avoid a second lumbar puncture; (Note: the CNS status must be determined based on a sample obtained prior to administration of any systemic or intrathecal chemotherapy, except for steroid pretreatment) systemic chemotherapy must begin within 72 hours of this intrathecal therapy
- •Patients receiving prior steroid therapy are eligible for this study; the dose and duration of previous steroid therapy should be carefully documented
- •Pregnancy tests with a negative result must be obtained in all post-menarchal females
- •Lactating females must agree that they will not breastfeed a child while on this study
排除标准
- •Patients with Down syndrome are excluded from this study
- •Patients with testicular leukemia at diagnosis are excluded from this study
- •Pregnant female patients are excluded from this study
研究组 & 干预措施
Arm I (combination chemotherapy)
Patients receive calaspargase pegol together with combination chemotherapy. Patients receive chemotherapy PO, IV, SC, and IT. Some patients also undergo radiation therapy to the head. Treatment may continue for up to 4 years.
干预措施: Calaspargase Pegol-mknl (Drug)
Arm I (combination chemotherapy)
Patients receive calaspargase pegol together with combination chemotherapy. Patients receive chemotherapy PO, IV, SC, and IT. Some patients also undergo radiation therapy to the head. Treatment may continue for up to 4 years.
干预措施: Cyclophosphamide (Drug)
Arm I (combination chemotherapy)
Patients receive calaspargase pegol together with combination chemotherapy. Patients receive chemotherapy PO, IV, SC, and IT. Some patients also undergo radiation therapy to the head. Treatment may continue for up to 4 years.
干预措施: Cytarabine (Drug)
Arm I (combination chemotherapy)
Patients receive calaspargase pegol together with combination chemotherapy. Patients receive chemotherapy PO, IV, SC, and IT. Some patients also undergo radiation therapy to the head. Treatment may continue for up to 4 years.
干预措施: Daunorubicin Hydrochloride (Drug)
Arm I (combination chemotherapy)
Patients receive calaspargase pegol together with combination chemotherapy. Patients receive chemotherapy PO, IV, SC, and IT. Some patients also undergo radiation therapy to the head. Treatment may continue for up to 4 years.
干预措施: Dexamethasone (Drug)
Arm I (combination chemotherapy)
Patients receive calaspargase pegol together with combination chemotherapy. Patients receive chemotherapy PO, IV, SC, and IT. Some patients also undergo radiation therapy to the head. Treatment may continue for up to 4 years.
干预措施: Doxorubicin Hydrochloride (Drug)
Arm I (combination chemotherapy)
Patients receive calaspargase pegol together with combination chemotherapy. Patients receive chemotherapy PO, IV, SC, and IT. Some patients also undergo radiation therapy to the head. Treatment may continue for up to 4 years.
干预措施: Laboratory Biomarker Analysis (Other)
Arm I (combination chemotherapy)
Patients receive calaspargase pegol together with combination chemotherapy. Patients receive chemotherapy PO, IV, SC, and IT. Some patients also undergo radiation therapy to the head. Treatment may continue for up to 4 years.
干预措施: Mercaptopurine (Drug)
Arm I (combination chemotherapy)
Patients receive calaspargase pegol together with combination chemotherapy. Patients receive chemotherapy PO, IV, SC, and IT. Some patients also undergo radiation therapy to the head. Treatment may continue for up to 4 years.
干预措施: Methotrexate (Drug)
Arm I (combination chemotherapy)
Patients receive calaspargase pegol together with combination chemotherapy. Patients receive chemotherapy PO, IV, SC, and IT. Some patients also undergo radiation therapy to the head. Treatment may continue for up to 4 years.
干预措施: Pegaspargase (Drug)
Arm I (combination chemotherapy)
Patients receive calaspargase pegol together with combination chemotherapy. Patients receive chemotherapy PO, IV, SC, and IT. Some patients also undergo radiation therapy to the head. Treatment may continue for up to 4 years.
干预措施: Pharmacological Study (Other)
Arm I (combination chemotherapy)
Patients receive calaspargase pegol together with combination chemotherapy. Patients receive chemotherapy PO, IV, SC, and IT. Some patients also undergo radiation therapy to the head. Treatment may continue for up to 4 years.
干预措施: Prednisone (Drug)
Arm I (combination chemotherapy)
Patients receive calaspargase pegol together with combination chemotherapy. Patients receive chemotherapy PO, IV, SC, and IT. Some patients also undergo radiation therapy to the head. Treatment may continue for up to 4 years.
干预措施: Radiation Therapy (Radiation)
Arm I (combination chemotherapy)
Patients receive calaspargase pegol together with combination chemotherapy. Patients receive chemotherapy PO, IV, SC, and IT. Some patients also undergo radiation therapy to the head. Treatment may continue for up to 4 years.
干预措施: Thioguanine (Drug)
Arm I (combination chemotherapy)
Patients receive calaspargase pegol together with combination chemotherapy. Patients receive chemotherapy PO, IV, SC, and IT. Some patients also undergo radiation therapy to the head. Treatment may continue for up to 4 years.
干预措施: Vincristine Sulfate (Drug)
Arm II (combination chemotherapy)
Patients receive pegaspargase together with combination chemotherapy. Patients receive chemotherapy PO, IV, SC, and IT. Some patients also undergo RT to the head. Treatment may continue for up to 4 years.
干预措施: Cyclophosphamide (Drug)
Arm II (combination chemotherapy)
Patients receive pegaspargase together with combination chemotherapy. Patients receive chemotherapy PO, IV, SC, and IT. Some patients also undergo RT to the head. Treatment may continue for up to 4 years.
干预措施: Cytarabine (Drug)
Arm II (combination chemotherapy)
Patients receive pegaspargase together with combination chemotherapy. Patients receive chemotherapy PO, IV, SC, and IT. Some patients also undergo RT to the head. Treatment may continue for up to 4 years.
干预措施: Daunorubicin Hydrochloride (Drug)
Arm II (combination chemotherapy)
Patients receive pegaspargase together with combination chemotherapy. Patients receive chemotherapy PO, IV, SC, and IT. Some patients also undergo RT to the head. Treatment may continue for up to 4 years.
干预措施: Dexamethasone (Drug)
Arm II (combination chemotherapy)
Patients receive pegaspargase together with combination chemotherapy. Patients receive chemotherapy PO, IV, SC, and IT. Some patients also undergo RT to the head. Treatment may continue for up to 4 years.
干预措施: Doxorubicin Hydrochloride (Drug)
Arm II (combination chemotherapy)
Patients receive pegaspargase together with combination chemotherapy. Patients receive chemotherapy PO, IV, SC, and IT. Some patients also undergo RT to the head. Treatment may continue for up to 4 years.
干预措施: Laboratory Biomarker Analysis (Other)
Arm II (combination chemotherapy)
Patients receive pegaspargase together with combination chemotherapy. Patients receive chemotherapy PO, IV, SC, and IT. Some patients also undergo RT to the head. Treatment may continue for up to 4 years.
干预措施: Mercaptopurine (Drug)
Arm II (combination chemotherapy)
Patients receive pegaspargase together with combination chemotherapy. Patients receive chemotherapy PO, IV, SC, and IT. Some patients also undergo RT to the head. Treatment may continue for up to 4 years.
干预措施: Methotrexate (Drug)
Arm II (combination chemotherapy)
Patients receive pegaspargase together with combination chemotherapy. Patients receive chemotherapy PO, IV, SC, and IT. Some patients also undergo RT to the head. Treatment may continue for up to 4 years.
干预措施: Pegaspargase (Drug)
Arm II (combination chemotherapy)
Patients receive pegaspargase together with combination chemotherapy. Patients receive chemotherapy PO, IV, SC, and IT. Some patients also undergo RT to the head. Treatment may continue for up to 4 years.
干预措施: Pharmacological Study (Other)
Arm II (combination chemotherapy)
Patients receive pegaspargase together with combination chemotherapy. Patients receive chemotherapy PO, IV, SC, and IT. Some patients also undergo RT to the head. Treatment may continue for up to 4 years.
干预措施: Prednisone (Drug)
Arm II (combination chemotherapy)
Patients receive pegaspargase together with combination chemotherapy. Patients receive chemotherapy PO, IV, SC, and IT. Some patients also undergo RT to the head. Treatment may continue for up to 4 years.
干预措施: Radiation Therapy (Radiation)
Arm II (combination chemotherapy)
Patients receive pegaspargase together with combination chemotherapy. Patients receive chemotherapy PO, IV, SC, and IT. Some patients also undergo RT to the head. Treatment may continue for up to 4 years.
干预措施: Thioguanine (Drug)
Arm II (combination chemotherapy)
Patients receive pegaspargase together with combination chemotherapy. Patients receive chemotherapy PO, IV, SC, and IT. Some patients also undergo RT to the head. Treatment may continue for up to 4 years.
干预措施: Vincristine Sulfate (Drug)
结局指标
主要结局
Pharmacokinetics (PK) (Half-life of SC-PEG E. Coli L-asparaginase (EZN-2285) Compared to Pegaspargase During Induction and Consolidation Therapy)
时间窗: Post Day 29 of Induction and Post Day 22 of Consolidation
Mean half-life of plasma asparaginase during consolidation and Induction; half-life is defined as the time taken for drug concentration to decrease by half.
次要结局
- Toxicities During Post Induction Intensification Therapy (All Grades)(Up to 5 years)
- Pharmacodynamics (PD)(Day 29 of consolidation and induction)
- Percentage of Participants With Minimal Residual Disease (MRD)<0.01% at the End of Induction(End of induction (Day 29))
- Percentage of Participants With Complete Remission at the End of Induction(End of induction (Day 29))
- Asparaginase Level(Days 4, 15, 22 and 29 of Induction)
- Plasma and CSF Concentrations of Asparagine in ug/ml(25 Days Post-dose (Day 29))
- Immunogenicity(25 Days Post-dose (Day 29))
- Percentage of Participants With Event-free Survival (EFS)(5 Years)
- Relationship Between PK and Presence of Antibodies(Day 29 of consolidation)