A Phase I Study of GTI2040 (NSC 722929; IND 67368) in Combination With High-dose Cytarabine in Refractory or Relapsed Acute Myeloid Leukemia (AML)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 51
- 试验地点
- 1
- 主要终点
- Maximum-tolerated dose (MTD) as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0
研究概览
简要总结
This phase I trial is studying the side effects and best dose of GTI-2040 and high-dose cytarabine in treating patients with refractory or relapsed acute myeloid leukemia. GTI-2040 may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth. Drugs used in chemotherapy, such as cytarabine, use different ways to stop cancer cells from dividing so they stop growing or die. Giving GTI-2040 together with cytarabine may kill more cancer cells.
详细描述
PRIMARY OBJECTIVES:
I. Determine the maximum tolerated dose and recommended phase II dose of GTI-2040 and high-dose cytarabine in patients with relapsed or refractory acute myeloid leukemia.
SECONDARY OBJECTIVES:
I. Determine the therapeutic response in patients treated with this regimen. II. Determine the pharmacokinetics of this regimen in these patients.
OUTLINE: This is a dose-escalation study. Patients are stratified according to age (under age 60 vs age 60 and over). Patients are assigned to 1 of 2 strata.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed acute myeloid leukemia according to the WHO classification
- •Relapsed or refractory disease, meeting 1 of the following criteria:
- •Unresponsive to initial treatment
- •Recurrent disease after treatment with prior conventional or high-dose chemotherapy with or without stem cell support
- •CNS involvement allowed provided there are no residual leukemic cells detected in the cerebrospinal fluid after intrathecal or radiation chemotherapy
- •Performance status - ECOG 0-2
- •At least 4 weeks
- •Bilirubin no greater than 2 times upper limit of normal* (ULN) (unless due to Gilbert's syndrome)
- •AST and ALT no greater than 3 times ULN*
- •Creatinine no greater than 1.5 mg/dL*
- •No symptomatic congestive heart failure
- •No unstable angina pectoris
- •No cardiac arrhythmia
- •Resting ejection fraction at least 50%*
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •No prior allergy to study medications
- •No ongoing or active infection requiring IV antibiotics
- •No other concurrent uncontrolled illness
- •No serious medical or psychiatric illness that would preclude giving informed consent
- •More than 4 weeks since prior chemotherapy (except hydroxyurea) (6 weeks for nitrosoureas or mitomycin)
- •No other concurrent chemotherapy
- •No concurrent hormonal therapy except steroids for adrenal failure and hormones for non-disease-related conditions (e.g., insulin for diabetes)
- •More than 4 weeks since prior radiotherapy
- •No concurrent palliative radiotherapy
- •Prior therapy with antisense oligonucleotides allowed provided no toxic effects were experienced that were directly attributable to the antisense agents
- •No other concurrent investigational agents
- •No other concurrent anticancer therapy
- •No concurrent chronic systemic anticoagulant therapy for medical conditions (e.g., prior deep vein thrombosis or atrial fibrillation)
- •Concurrent heparin to maintain central line patency (i.e., catheter flush) is allowed
- •No concurrent combination antiretroviral therapy for HIV-positive patients
排除标准
- 未提供
研究组 & 干预措施
Stratum I (GTI-2040, cytarabine)
Patients receive GTI-2040 IV continuously on days 1-6 and high-dose cytarabine IV over 2 hours twice daily on days 2, 4, and 6.
干预措施: GTI-2040 (Biological)
Stratum I (GTI-2040, cytarabine)
Patients receive GTI-2040 IV continuously on days 1-6 and high-dose cytarabine IV over 2 hours twice daily on days 2, 4, and 6.
干预措施: cytarabine (Drug)
Stratum I (GTI-2040, cytarabine)
Patients receive GTI-2040 IV continuously on days 1-6 and high-dose cytarabine IV over 2 hours twice daily on days 2, 4, and 6.
干预措施: pharmacological study (Other)
Stratum I (GTI-2040, cytarabine)
Patients receive GTI-2040 IV continuously on days 1-6 and high-dose cytarabine IV over 2 hours twice daily on days 2, 4, and 6.
干预措施: laboratory biomarker analysis (Other)
Stratum II (GTI-2040, cytarabine)
Patients receive GTI-2040 IV continuously on days 1-6 and high-dose cytarabine IV over 4 hours once daily on days 2-6. In both strata, treatment continues in the absence of unacceptable toxicity.
干预措施: GTI-2040 (Biological)
Stratum II (GTI-2040, cytarabine)
Patients receive GTI-2040 IV continuously on days 1-6 and high-dose cytarabine IV over 4 hours once daily on days 2-6. In both strata, treatment continues in the absence of unacceptable toxicity.
干预措施: cytarabine (Drug)
Stratum II (GTI-2040, cytarabine)
Patients receive GTI-2040 IV continuously on days 1-6 and high-dose cytarabine IV over 4 hours once daily on days 2-6. In both strata, treatment continues in the absence of unacceptable toxicity.
干预措施: pharmacological study (Other)
Stratum II (GTI-2040, cytarabine)
Patients receive GTI-2040 IV continuously on days 1-6 and high-dose cytarabine IV over 4 hours once daily on days 2-6. In both strata, treatment continues in the absence of unacceptable toxicity.
干预措施: laboratory biomarker analysis (Other)
结局指标
主要结局
Maximum-tolerated dose (MTD) as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0
时间窗: Up to day 42
次要结局
- Therapeutic response(Up to 6 years)
- Change in R2 expression in circulating and marrow leukemia cells(From baseline to up to 6 years)