Dose Escalation and Phase II Study of Bortezomib (IND #58443) Added to Standard Daunorubicin and Cytarabine Therapy for Patients With Previously Untreated Acute Myeloid Leukemia Age 60-75 Years
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 95
- 试验地点
- 22
- 主要终点
- Remission Induction Response
研究概览
简要总结
This phase II trial studies the side effects and best dose of bortezomib when given together with daunorubicin and cytarabine and to see how well it works in treating older patients with previously untreated acute myeloid leukemia. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as daunorubicin and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving bortezomib together with combination chemotherapy may kill more cancer cells.
详细描述
PRIMARY OBJECTIVES:
I. To define the remission induction response rate (complete response [CR] and CR with incomplete platelet recovery [CRp]) in older patients with previously untreated acute myeloid leukemia treated with induction therapy comprising bortezomib in combination with daunorubicin hydrochloride and cytarabine.
II. To define the maximum tolerated dose of bortezomib when administered in combination with intermediate-dose cytarabine after induction therapy.
SECONDARY OBJECTIVES:
I. To describe the disease-free survival of patients treated with this regimen. II. To describe the overall survival of patients treated with this regimen. III. To evaluate the treatment-related toxicities in these patients.
研究设计
- 研究类型
- Interventional
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 60 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Unequivocally histologically confirmed acute myeloid leukemia (AML)
- •At least 20% blasts in the bone marrow based on WHO criteria
- •No acute promyelocytic leukemia (M3)
- •Antecedent hematologic disorder or myelodysplastic syndromes allowed provided the patient did not receive cytotoxic chemotherapy, including azacitidine and decitabine, for their pre-leukemic disorder
- •Concurrent enrollment on CALGB-8461 required
- •Not pregnant or nursing
- •Fertile patients must use effective contraception
- •No ataxia, cranial neuropathy, or peripheral neuropathy >= grade 2
- •LVEF >= 40% by ECHO or MUGA scan
- •No signs or symptoms of congestive heart failure
- •DLCO >= 50% (corrected for hemoglobin)
- •No prior therapy for leukemia or pre-leukemic disorders, except for the following:
- •emergency leukapheresis;
- •emergency treatment for hyperleukocytosis with hydroxyurea;
- •cranial radiotherapy for CNS leukostasis (one dose only);
- •growth factor/cytokine support
- •No other concurrent chemotherapy, except for the following:
- •I) steroids administered for adrenal failure, hypersensitivity reactions, or septic shock;
- •II) hormones administered for non-disease-related conditions (e.g., insulin for diabetes or estrogens or progestins for gynecologic indications)
- •No concurrent palliative radiotherapy
排除标准
- 未提供
研究组 & 干预措施
Treatment (daunorubicin hydrochloride and bortezomib)
See Detailed Description
干预措施: daunorubicin hydrochloride (Drug)
Treatment (daunorubicin hydrochloride and bortezomib)
See Detailed Description
干预措施: cytarabine (Drug)
Treatment (daunorubicin hydrochloride and bortezomib)
See Detailed Description
干预措施: bortezomib (Drug)
结局指标
主要结局
Remission Induction Response
时间窗: 2 months
Response was calculated according to Revised International Working Group (IWG) criteria for Acute myeloid leukemia (AML) A response was defined as the portion of participants who achieved a complete response (CR) or CR with incomplete platelet recovery(CRp) during induction. A CR is defined as those with \> 20% cellularity of bone marrow biopsy, no presence of extramedullary leukemia for AML, \<5 % myeloblast cells for bone marrow with peripheral blood and normal complete blood count (absolute neutrophils \> 1000 mL and platelets \>= 100,000 mL). A CRp is defined as a CR except platelets \< 100,000 mL without need for transfusion.
Participants Experiencing a Dose-limiting Toxicity (DLT) of Bortezomib When Administered in Combination With Intermediate-dose Cytarabine
时间窗: during consolidation cycle 1 (42 days)
DLTs were considered only during the first cycle of consolidation therapy and included grade 3 or 4 sensory or autonomic neuropathy, persistent grade 4 thrombocytopenia or neutropenia at day 42 in the absence of AML,any grade 4 or 5 nonhematologic toxicity, and any grade 3 nonhematologic toxicity (excluding neuropathy and toxicities secondary to neutropenia and sepsis) that did not resolve to grade 2 by day 42 unless attributable to persistent or recurrent AML. Grade 4 anorexia (requiring total parenteral nutrition) and grade 4 fatigue (requiring bed rest) were not considered DLTs. Toxicity was graded per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. Grading scale is as follows: grade 1: mild; grade 2: moderate; grade 3: Severe; grade 4: Life Threatening; grade 5: Death.
次要结局
- Disease-free Survival(Duration of study (up to 10 years))
- Overall Survival(Duration of study (up to 10 years))