Randomized Phase II Trial of Idarubicin + Ara-C +/- Bevacizumab in Patients Age < 60 With Untreated Acute Myeloid Leukemia
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 120
- 试验地点
- 1
- 主要终点
- Proportion of patients who remain alive in the first complete remission (CR) 1 year from achievement of CR assessed every 3 weeks for 1 year
研究概览
简要总结
Drugs used in chemotherapy, such as idarubicin and cytarabine, work in different ways to stop cancer cells from dividing so they stop growing or die. Bevacizumab may stop the growth of cancer by stopping blood flow to the leukemic cells in the bone marrow. Giving idarubicin and cytarabine with bevacizumab may kill more cancer cells. It is not yet know whether giving idarubicin together with cytarabine is more effective with or without bevacizumab in treating acute myeloid leukemia. This randomized phase II trial is studying how well giving idarubicin and cytarabine together with bevacizumab works compared to idarubicin and cytarabine alone in treating patients with newly diagnosed acute myeloid leukemia
详细描述
PRIMARY OBJECTIVES:
I. Compare the activity of idarubicin and cytarabine with or without bevacizumab in patients with newly diagnosed acute myeloid leukemia.
II. Compare the proportion of patients who survive and remain in first complete remission (CR) one year from achieving CR after treatment with these regimens.
SECONDARY OBJECTIVES:
I. Compare the safety of these regimens in these patients.
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
- — 至 59 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Newly diagnosed acute myeloid leukemia (AML)
- •No acute promyelocytic leukemia
- •None of the following cytogenetic abnormalities*:
- •No history or clinical evidence of primary brain tumors or brain metastasis
- •Performance status - ECOG 0-2
- •No bleeding diathesis or coagulopathy (unless related to AML)
- •Bilirubin ≤ 2.0 times upper limit of normal (ULN)
- •ALT ≤ 2.5 times ULN
- •Creatinine ≤ 2.0 times ULN
- •No proteinuria
- •No more than 1 g of protein on 24-hour urine collection
- •LVEF ≥ 50%
- •No uncontrolled hypertension
- •No New York Heart Association class II-IV congestive heart failure
- •No serious cardiac arrhythmia requiring medication
- •No peripheral vascular disease ≥ grade II
- •No stroke within the past 6 months
- •No arterial thromboembolic event within the past 6 months, including any of the following:
- •Transient ischemic attack
- •Cerebrovascular accident
- •Myocardial infarction
- •Unstable angina
- •No other clinically significant cardiovascular disease
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception during and for at least 3-4 months after study participation
- •No serious or non-healing wound ulcer or bone fracture
- •No uncontrolled infection
- •No significant traumatic injury within the past 28 days
- •No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
- •No history or clinical evidence of CNS disease (e.g., seizures not controlled with standard medical therapy)
- •Prior or concurrent transfusions or hematopoietic growth factors for AML allowed
- •No concurrent prophylactic hematopoietic colony-stimulating factors
- •Prior or concurrent hydroxyurea for AML allowed
- •More than 28 days since prior major surgery or open biopsy
- •No concurrent major surgery
- •No other prior therapy for AML
- •No concurrent full-dose anticoagulation therapy
- •Concurrent prophylactic anticoagulation (e.g. low-dose warfarin to maintain patency of permanent indwelling IV catheters) allowed provided INR < 1.5
- •No other concurrent anticancer therapies
- •No other concurrent investigational cytotoxic agents
排除标准
- 未提供
研究组 & 干预措施
Arm I (idarubicin, cytarabine)
Arm I: Patients receive idarubicin IV over 1 hour on days 1-3 and cytarabine IV continuously over 24 hours on days 1-4.
Post-CR therapy: All patients receive 4 post-CR chemotherapy courses approximately every 28 days in the absence of disease progression or unacceptable toxicity.
Course 1: Patients receive cytarabine IV continuously over 24 hours on days 1-5.
Course 2 and 4: Patients receive idarubicin IV over 1 hour and cytarabine IV continuously over 24 hours on days 1-4.
干预措施: idarubicin (Drug)
Arm I (idarubicin, cytarabine)
Arm I: Patients receive idarubicin IV over 1 hour on days 1-3 and cytarabine IV continuously over 24 hours on days 1-4.
Post-CR therapy: All patients receive 4 post-CR chemotherapy courses approximately every 28 days in the absence of disease progression or unacceptable toxicity.
Course 1: Patients receive cytarabine IV continuously over 24 hours on days 1-5.
Course 2 and 4: Patients receive idarubicin IV over 1 hour and cytarabine IV continuously over 24 hours on days 1-4.
干预措施: cytarabine (Drug)
Arm I (idarubicin, cytarabine)
Arm I: Patients receive idarubicin IV over 1 hour on days 1-3 and cytarabine IV continuously over 24 hours on days 1-4.
Post-CR therapy: All patients receive 4 post-CR chemotherapy courses approximately every 28 days in the absence of disease progression or unacceptable toxicity.
Course 1: Patients receive cytarabine IV continuously over 24 hours on days 1-5.
Course 2 and 4: Patients receive idarubicin IV over 1 hour and cytarabine IV continuously over 24 hours on days 1-4.
干预措施: laboratory biomarker analysis (Other)
Arm II (idarubicin, cytarabine, bevacizumab)
Patients receive idarubicin and cytarabine as in arm I. Patients also receive bevacizumab* IV over 30-90 minutes on day 1. Patients who do not achieve complete remission (CR) after the first induction course may receive a second induction course approximately 28 days* later. Patients who do not achieve CR after 2 courses are removed from the study.
NOTE: *Patients in arm II receive bevacizumab, independently of chemotherapy administration schedule, once every 21 days for 1 year from CR date.
Post-CR therapy: All patients receive 4 post-CR chemotherapy courses approximately every 28 days in the absence of disease progression or unacceptable toxicity.
Course 1: Patients receive cytarabine IV continuously over 24 hours on days 1-5.
Course 2 and 4: Patients receive idarubicin IV over 1 hour and cytarabine IV continuously over 24 hours on days 1-4.
干预措施: idarubicin (Drug)
Arm II (idarubicin, cytarabine, bevacizumab)
Patients receive idarubicin and cytarabine as in arm I. Patients also receive bevacizumab* IV over 30-90 minutes on day 1. Patients who do not achieve complete remission (CR) after the first induction course may receive a second induction course approximately 28 days* later. Patients who do not achieve CR after 2 courses are removed from the study.
NOTE: *Patients in arm II receive bevacizumab, independently of chemotherapy administration schedule, once every 21 days for 1 year from CR date.
Post-CR therapy: All patients receive 4 post-CR chemotherapy courses approximately every 28 days in the absence of disease progression or unacceptable toxicity.
Course 1: Patients receive cytarabine IV continuously over 24 hours on days 1-5.
Course 2 and 4: Patients receive idarubicin IV over 1 hour and cytarabine IV continuously over 24 hours on days 1-4.
干预措施: cytarabine (Drug)
Arm II (idarubicin, cytarabine, bevacizumab)
Patients receive idarubicin and cytarabine as in arm I. Patients also receive bevacizumab* IV over 30-90 minutes on day 1. Patients who do not achieve complete remission (CR) after the first induction course may receive a second induction course approximately 28 days* later. Patients who do not achieve CR after 2 courses are removed from the study.
NOTE: *Patients in arm II receive bevacizumab, independently of chemotherapy administration schedule, once every 21 days for 1 year from CR date.
Post-CR therapy: All patients receive 4 post-CR chemotherapy courses approximately every 28 days in the absence of disease progression or unacceptable toxicity.
Course 1: Patients receive cytarabine IV continuously over 24 hours on days 1-5.
Course 2 and 4: Patients receive idarubicin IV over 1 hour and cytarabine IV continuously over 24 hours on days 1-4.
干预措施: bevacizumab (Biological)
Arm II (idarubicin, cytarabine, bevacizumab)
Patients receive idarubicin and cytarabine as in arm I. Patients also receive bevacizumab* IV over 30-90 minutes on day 1. Patients who do not achieve complete remission (CR) after the first induction course may receive a second induction course approximately 28 days* later. Patients who do not achieve CR after 2 courses are removed from the study.
NOTE: *Patients in arm II receive bevacizumab, independently of chemotherapy administration schedule, once every 21 days for 1 year from CR date.
Post-CR therapy: All patients receive 4 post-CR chemotherapy courses approximately every 28 days in the absence of disease progression or unacceptable toxicity.
Course 1: Patients receive cytarabine IV continuously over 24 hours on days 1-5.
Course 2 and 4: Patients receive idarubicin IV over 1 hour and cytarabine IV continuously over 24 hours on days 1-4.
干预措施: laboratory biomarker analysis (Other)
结局指标
主要结局
Proportion of patients who remain alive in the first complete remission (CR) 1 year from achievement of CR assessed every 3 weeks for 1 year
时间窗: 13 months from registration
Fisher's exact test will be used to compare the proportion of patients alive in CR 13 months from registration date. The test has approximately 89% power to detect an absolute increase of 20% in this proportion, testing at the one-sided 0.15 significance level.
次要结局
- Safety of idarubicin+cytarabine+bevacizumab by AdEERS, CBC and chem.(Up to 2 years after study completion)