Phase Ib Study of Fludarabine, Cytarabine (Ara-C) and Pegylated Erwinase (Pegcrisantaspase) in Patients with Relapsed or Refractory Leukemia
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 19
- 试验地点
- 1
- 主要终点
- Maximum tolerated dose (MTD)
研究概览
简要总结
This phase Ib trial investigates the side effects and best dose of pegcrisantaspase when given together with fludarabine and cytarabine for the treatment of patients with leukemia that has come back (relapsed) or has not responded to treatment (refractory). Pegcrisantaspase may block the growth of cancer cells. Chemotherapy drugs, such as fludarabine and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving pegcrisantaspase in combination with fludarabine and cytarabine may work better in treating patients with leukemia compared to the combination of fludarabine and cytarabine.
详细描述
PRIMARY OBJECTIVE:
I. To determine the safety and tolerability of fludarabine, cytarabine (araC), and pegcrisantaspase in patients with relapsed and refractory leukemias.
SECONDARY OBJECTIVES:
I. To determine the overall response rate (complete remission [CR], CR with incomplete count recovery [CRi], partial remission [PR], or morphologic leukemia free state [MLFS]) of a lead-in dose of single-agent pegcrisantaspase in patients with relapsed and refractory leukemias.
II. To determine the overall response rate (complete remission [CR], CR with incomplete count recovery [CRi], partial remission [PR], or morphologic leukemia free state [MLFS]) of fludarabine, araC, and pegcrisantaspase in patients with relapsed and refractory leukemias.
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
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with a diagnosis of relapsed or refractory leukemia including, but not limited to acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), T-cell prolymphocytic leukemia, biphenotypic acute leukemia, or blast-phase of chronic myeloid Leukemia (CML) will be allowed during the safety lead-in phase
- •For cohort A of the expansion phase: Patients with a diagnosis untreated adverse-risk AML (as defined by ELN [European Leukemia Net Classification] 2017) will be enrolled
- •For cohort B of the expansion phase: Patients with a diagnosis of relapsed or refractory AML will be enrolled
- •Bilirubin =< 2 mg/dL
- •Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) =< 2.5 x upper limit of normal (ULN)
- •Creatinine =< 1.5 x ULN
- •Cardiac ejection fraction of > or = 45% within the past 3 months
- •Amylase and lipase =< 1.5 x ULN
- •Eastern Cooperative Oncology Group (ECOG) performance status of =< 2
- •A negative urine pregnancy test is required within one week (7 days) for all women of childbearing potential prior to being registered on this trial
- •Patient must have the ability to understand the requirements of the study and signed informed consent. A signed informed consent by the patient or his legally authorized representative is required prior to their enrollment on the protocol
排除标准
- •Pregnant women are excluded from this study because the agents used in this study have the potential for teratogenic or abortifacient effects. Because there is a potential risk for adverse events in nursing infants secondary to treatment of the mother with the chemotherapy agents, breastfeeding should also be avoided
- •Uncontrolled intercurrent illness including, but not limited to active uncontrolled infection, symptomatic congestive heart failure (New York Heart Association [NYHA] class III or IV), unstable angina pectoris, clinically significant cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- •Patient with documented hypersensitivity to any of the components of the chemotherapy program
- •Prior treatment with pegylated asparaginase
- •Patients with a diagnoses of acute promyelocytic leukemia (AML-M3) will be excluded from this trial
- •Men and women of childbearing potential who do not practice contraception. Women of childbearing potential and men must agree to use contraception prior to study entry and for the duration of study participation. Effective methods of birth control include:
- •Birth control pills, shots, implants or patches
- •Intrauterine devices (IUDs)
- •Condom or occlusive cap (diaphragm or cervical/vault caps) used with spermicide
- •Abstinence
- •Females of non-childbearing potential are those who are postmenopausal greater than 1 year or who have had a bilateral tubal ligation, oophorectomy, and/or hysterectomy
- •Patients with history of clinically significant venous thromboembolism
研究组 & 干预措施
Treatment (pegcrisantaspase, fludarabine, cytarabine)
INDUCTION: Patients receive pegcrisantaspase IV over 60 minutes on days 1 and 15, and fludarabine IV over 15-30 minutes and cytarabine IV over 2 hours on days 8-11 in the absence of disease progression or unacceptable toxicity.
CONSOLIDATION: Patients receive pegcrisantaspase IV over 60 minutes on days 1 and 15, and fludarabine IV over 15-30 minutes and cytarabine IV over 2 hours on days 8-10. Treatment repeats every 5 weeks for up 3 cycles in the absence of disease progression or unacceptable toxicity.
干预措施: Cytarabine (Drug)
Treatment (pegcrisantaspase, fludarabine, cytarabine)
INDUCTION: Patients receive pegcrisantaspase IV over 60 minutes on days 1 and 15, and fludarabine IV over 15-30 minutes and cytarabine IV over 2 hours on days 8-11 in the absence of disease progression or unacceptable toxicity.
CONSOLIDATION: Patients receive pegcrisantaspase IV over 60 minutes on days 1 and 15, and fludarabine IV over 15-30 minutes and cytarabine IV over 2 hours on days 8-10. Treatment repeats every 5 weeks for up 3 cycles in the absence of disease progression or unacceptable toxicity.
干预措施: Fludarabine (Drug)
Treatment (pegcrisantaspase, fludarabine, cytarabine)
INDUCTION: Patients receive pegcrisantaspase IV over 60 minutes on days 1 and 15, and fludarabine IV over 15-30 minutes and cytarabine IV over 2 hours on days 8-11 in the absence of disease progression or unacceptable toxicity.
CONSOLIDATION: Patients receive pegcrisantaspase IV over 60 minutes on days 1 and 15, and fludarabine IV over 15-30 minutes and cytarabine IV over 2 hours on days 8-10. Treatment repeats every 5 weeks for up 3 cycles in the absence of disease progression or unacceptable toxicity.
干预措施: Pegcrisantaspase (Drug)
结局指标
主要结局
Maximum tolerated dose (MTD)
时间窗: End of cycle 1 (5 weeks)
Measured by dose limiting toxicities (DLTs). DLTs will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE, version 5) by organ system. DLT will be defined as drug-related adverse events during cycle one (during the lead-in phase).
次要结局
- Overall response rate (ORR) of pegcrisantaspase(Up to 20 weeks)
- ORR of fludarabine, cytarabine (araC), and pegcrisantaspase(Up to 20 weeks)
- Overall survival (OS)(From date of treatment start until date of death due to any cause, assessed up to 20 weeks)
- Disease-free survival (DFS)(From date of remission until the date of first objective documentation ofdisease-relapse or death, assessed up to 20 weeks)
- Duration of response(Up to 20 weeks)