A Phase I Study of G3139 ( NSC # 683428) in Combination With Cytarabine and Daunorubicin in Previously Untreated Patients With Acute Myeloid Leukemia (AML)>= 60 Years of Age
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 32
- 试验地点
- 1
- 主要终点
- Incidence of adverse events, graded according to NCI CTC version 2.0
研究概览
简要总结
Phase I trial to study the effectiveness of combining oblimersen with cytarabine and daunorubicin in treating older patients who have previously untreated acute myeloid leukemia. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Oblimersen may help cytarabine and daunorubicin kill more cancer cells by making them more sensitive to chemotherapy.
详细描述
OBJECTIVES:
I. Determine the maximum tolerated dose of daunorubicin in combination with cytarabine and oblimersen in older patients with previously untreated acute myeloid leukemia.
II. Determine the qualitative and quantitative toxic effects of this regimen in these patients.
III. Determine the pharmacokinetics of oblimersen in this regimen in these patients.
IV. Determine the disease-free survival and overall survival of patients treated with this regimen.
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
- 60 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed primary or secondary acute myeloid leukemia (AML)
- •More than 20% bone marrow blasts
- •Myelodysplastic syndromes (MDS) or a chronic myeloproliferative disorder antecedent to AML allowed
- •Therapy-related AML allowed
- •No acute promyelocytic leukemia
- •At least 4 weeks
- •Bilirubin no greater than 2 mg/dL
- •ALT and AST no greater than 2 times upper limit of normal (unless directly attributable to AML)
- •Creatinine no greater than 2.5 mg/dL
- •Ejection fraction at least 50% by MUGA or echocardiogram
- •No symptomatic congestive heart failure
- •No unstable angina pectoris
- •No cardiac arrhythmia
- •No allergy to any of the study medications
- •No other uncontrolled concurrent illness
- •No serious medical or psychiatric illness that would preclude giving informed consent
- •Not pregnant or nursing
- •Fertile patients must use effective contraception
- •No prior therapy for primary AML except emergency leukapheresis
- •No prior anthracyclines
- •No prior chemotherapy for primary AML except hydroxyurea for hyperleukocytosis
- •At least 3 months since prior chemotherapy for MDS or chronic myeloproliferative disorders antecedent to AML
- •No other concurrent chemotherapy
- •No concurrent corticosteroids as anti-emetics
- •No concurrent steroids except for adrenal failure or septic shock
- •No concurrent hormonal therapy except hormones for non-disease-related conditions (e.g., insulin for diabetes, tamoxifen or equivalent for breast cancer prevention or adjuvant treatment, or estrogens or progestins for gynecologic indications)
- •No prior radiotherapy for primary AML except cranial radiotherapy for CNS leukostasis
- •No concurrent palliative radiotherapy
- •No concurrent whole brain radiotherapy
- •No other concurrent investigational or commercial agents or therapies
- •No concurrent cyclooxygenase-2 inhibitors
排除标准
- 未提供
研究组 & 干预措施
Arm I
INDUCTION THERAPY: Patients receive oblimersen (G3139) IV continuously on days 1-10 and cytarabine IV continuously on days 4-10. Patients also receive daunorubicin IV daily on days 4-6.
Patients with bone marrow cellularity of at least 20% and at least 5% leukemic blasts at day 17 or evidence of refractory disease receive a second induction comprising G3139 IV continuously on days 1-8, cytarabine IV continuously on days 4-8, and daunorubicin IV on days 4-5.
CONSOLIDATION THERAPY: Beginning no sooner than 14 days after hematologic recovery from induction therapy, patients receive G3139 IV continuously on days 1-8 and cytarabine IV over 4 hours on days 4-8. Patients receive a second course of consolidation therapy no sooner than 14 days after hematologic recovery from the first course.
干预措施: oblimersen sodium (Biological)
Arm I
INDUCTION THERAPY: Patients receive oblimersen (G3139) IV continuously on days 1-10 and cytarabine IV continuously on days 4-10. Patients also receive daunorubicin IV daily on days 4-6.
Patients with bone marrow cellularity of at least 20% and at least 5% leukemic blasts at day 17 or evidence of refractory disease receive a second induction comprising G3139 IV continuously on days 1-8, cytarabine IV continuously on days 4-8, and daunorubicin IV on days 4-5.
CONSOLIDATION THERAPY: Beginning no sooner than 14 days after hematologic recovery from induction therapy, patients receive G3139 IV continuously on days 1-8 and cytarabine IV over 4 hours on days 4-8. Patients receive a second course of consolidation therapy no sooner than 14 days after hematologic recovery from the first course.
干预措施: cytarabine (Drug)
Arm I
INDUCTION THERAPY: Patients receive oblimersen (G3139) IV continuously on days 1-10 and cytarabine IV continuously on days 4-10. Patients also receive daunorubicin IV daily on days 4-6.
Patients with bone marrow cellularity of at least 20% and at least 5% leukemic blasts at day 17 or evidence of refractory disease receive a second induction comprising G3139 IV continuously on days 1-8, cytarabine IV continuously on days 4-8, and daunorubicin IV on days 4-5.
CONSOLIDATION THERAPY: Beginning no sooner than 14 days after hematologic recovery from induction therapy, patients receive G3139 IV continuously on days 1-8 and cytarabine IV over 4 hours on days 4-8. Patients receive a second course of consolidation therapy no sooner than 14 days after hematologic recovery from the first course.
干预措施: daunorubicin hydrochloride (Drug)
Arm I
INDUCTION THERAPY: Patients receive oblimersen (G3139) IV continuously on days 1-10 and cytarabine IV continuously on days 4-10. Patients also receive daunorubicin IV daily on days 4-6.
Patients with bone marrow cellularity of at least 20% and at least 5% leukemic blasts at day 17 or evidence of refractory disease receive a second induction comprising G3139 IV continuously on days 1-8, cytarabine IV continuously on days 4-8, and daunorubicin IV on days 4-5.
CONSOLIDATION THERAPY: Beginning no sooner than 14 days after hematologic recovery from induction therapy, patients receive G3139 IV continuously on days 1-8 and cytarabine IV over 4 hours on days 4-8. Patients receive a second course of consolidation therapy no sooner than 14 days after hematologic recovery from the first course.
干预措施: laboratory biomarker analysis (Other)
Arm I
INDUCTION THERAPY: Patients receive oblimersen (G3139) IV continuously on days 1-10 and cytarabine IV continuously on days 4-10. Patients also receive daunorubicin IV daily on days 4-6.
Patients with bone marrow cellularity of at least 20% and at least 5% leukemic blasts at day 17 or evidence of refractory disease receive a second induction comprising G3139 IV continuously on days 1-8, cytarabine IV continuously on days 4-8, and daunorubicin IV on days 4-5.
CONSOLIDATION THERAPY: Beginning no sooner than 14 days after hematologic recovery from induction therapy, patients receive G3139 IV continuously on days 1-8 and cytarabine IV over 4 hours on days 4-8. Patients receive a second course of consolidation therapy no sooner than 14 days after hematologic recovery from the first course.
干预措施: pharmacological study (Other)
结局指标
主要结局
Incidence of adverse events, graded according to NCI CTC version 2.0
时间窗: Up to 2 years
We will define the qualitative and quantitative toxicities in regard to organ specificity, time course, predictability, and reversibility.
MTD of cytarabine and daunorubicin in combination with G3139, defined as the dose level just below the dose level at which DLT is observed in 2 patients, graded according to NCI CTC version 2.0
时间窗: Up to day 10
次要结局
- Overall survival(Up to 2 years)
- Level of bcl-2 in circulating and/or marrow leukemic blasts before and after initiation of treatment with G3139(Up to 18 weeks)
- Spontaneous rate of apoptosis in leukemic blasts before and after initiation of treatment with G3139(Up to 18 weeks)
- Pharmacokinetics of G3139(During induction therapy on day 1 at hour 0 and 24hours after G3139 administration; day 4 at hour 73 before cytarabine administration; day 11 at hour 0 and .5, 1, 2, 4, 6, and 8 hours)
- Incidence of therapeutic response (complete remission [CR])(Up to 2 years)
- Disease-free survival(Up to 2 years)