NCT00093639已完成1 期
A Phase I-II, Study of RAD001 in Combination With Imatinib (Glivec®/Gleevec™) in Patients With Chronic Myelogenous Leukemia (CML) in Chronic Phase Who Are Not In Complete Cytogenetic Response to Imatinib-Alone at Study Entry
适应症
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 试验地点
- 2
- 主要终点
- Tolerability and biological activity of everolimus and imatinib mesylate every 6 months after completion of study treatment
研究概览
简要总结
RATIONALE: Drugs used in chemotherapy, such as everolimus, work in different ways to stop cancer cells from dividing so they stop growing or die. Imatinib mesylate may stop the growth of cancer cells by blocking the enzymes necessary for their growth. Combining everolimus with imatinib mesylate may be effective in killing cancer cells that have become resistant to imatinib mesylate.
PURPOSE: This phase I/II trial is studying the side effects and best dose of everolimus when given together with imatinib mesylate and to see how well they work in treating patients with chronic phase chronic myelogenous leukemia who are not in complete cytogenetic remission after previous imatinib mesylate.
详细描述
OBJECTIVES:
Primary
- Determine the safety, tolerability, and biological activity of everolimus when combined with imatinib mesylate in patients with chronic phase chronic myelogenous leukemia that is not in complete cytogenetic remission after prior imatinib mesylate. (Phase I)
- Determine, preliminarily, the clinical efficacy of this regimen, in terms of 3-month improvement by at least one cytogenetic category and the duration of cytogenetic improvements, in these patients. (Phase II)
Secondary
- Determine the 6-month rate of cytogenetic improvements in patients treated with this regimen.
- Determine the rate of confirmed cytogenetic improvements in patients treated with this regimen.
- Determine the rate and duration of major cytogenetic response in patients treated with this regimen.
- Determine the rate and kinetics of molecular response in patients treated with this regimen.
- Correlate genetic variation in drug metabolism genes, leukemia genes, and drug target genes with response in patients treated with this regimen.
- Determine the pharmacokinetics of this regimen in these patients.
- Determine whether the mTOR pathway activity, as determined by molecular pathologic examination before and during treatment with this regimen, is predictive of response in these patients.
研究设计
- 研究类型
- Interventional
- 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
- •DISEASE CHARACTERISTICS:
- •Histologically confirmed chronic myelogenous leukemia (CML)
- •In chronic phase
- •Philadelphia chromosome (Ph)-positive
- •No accelerated or blastic phase
- •Accelerated phase CML is defined as ≥ 15% but < 30% blasts in peripheral blood or bone marrow OR ≥ 30% blasts and promyelocytes in peripheral blood or bone marrow provided that < 30% blasts were present OR ≥ 20% peripheral basophils OR platelet count < 100,000/mm^3, unrelated to therapy
- •No less than 20 metaphases in the bone marrow sample
- •No evidence of complete cytogenetic response to imatinib mesylate (complete cytogenetic response defined as 0% Ph-positive cells in bone marrow)
- •Receiving continuous imatinib mesylate therapy for ≥ the past 9 months
- •Dosage ≥ 600 mg/day for ≥ the past 3 months
- •Stable dose of 600 mg/day for ≥ the past 4 weeks
- •Achieved and maintained hematological response to imatinib mesylate as defined by all of the following:
- •WBC < 20,000/mm^3
- •Basophils < 20%
- •Less than 5% myelocytes and metamyelocytes in peripheral blood
- •No blasts or promyelocytes in peripheral blood
- •No evidence of disease-related symptoms or extramedullary disease, including enlarged spleen or liver
- •PATIENT CHARACTERISTICS:
- •18 and over
- •Performance status
- •Life expectancy
- •Not specified
- •Hematopoietic
- •See Disease Characteristics
- •Absolute neutrophil count ≥ 1,500/mm^3
- •Platelet count ≥ 100,000/mm^3
- •Hemoglobin ≥ 9 g/dL
- •AST and ALT < 1.5 times upper limit of normal (ULN)
- •Bilirubin < 1.5 times ULN (except for patients with Gilbert's disease)
- •PTT < 1.5 times ULN (except for patients on oral anticoagulation therapy)
- •INR < 1.5 times ULN (except for patients on oral anticoagulation therapy)
- •Creatinine < 1.5 times ULN
- •Cardiovascular
- •No angina
- •No New York Heart Association class III or IV cardiac disease
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective barrier contraception during and for 3 months after study participation
- •HIV negative
- •No history of non-compliance with medical regimens
- •No hypercholesterolemia or hypertriglyceridemia (fasting state) ≥ grade 2 (despite lipid-lowering therapy)
- •No diabetes mellitus
- •No thyroid dysfunction
- •No neuropsychiatric disorders
- •No infection
- •No other severe and/or uncontrolled medical condition that would preclude study participation
- •No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
- •PRIOR CONCURRENT THERAPY:
- •Biologic therapy
- •No prior allogeneic, syngeneic, or autologous bone marrow transplantation or stem cell transplantation for CML
- 另有 12 项未显示
排除标准
- 未提供
结局指标
主要结局
Tolerability and biological activity of everolimus and imatinib mesylate every 6 months after completion of study treatment
次要结局
- Cytogenetic improvements at 3 and 6 months and then every 6 months after completion of study treatment
- Changes in the amounts of the Bcr-Abl transcripts as measured by quantitative real time reverse transcriptase PCR (QT-PCR) every 6 months after completion of study treatment
- mTOR pathway activity at baseline and during treatment measured by molecular pathological examination of blood and bone marrow cells every 6 months after completion of study treatment
- Disease-related mutations and gene expression changes in blood, bone marrow cells, and in plasma every 6 months after completion of study treatment
- Effects of genetic variation in drug metabolism genes, leukemia genes, and drug target genes on patient response measured every 6 months after completion of study treatment
- Pharmacokinetics of combination everolimus and imatinib every 6 months after completion of study treatment
研究者
研究点 (2)
Loading locations...
相似试验
已完成
2 期
Everolimus in Treating Patients With Stage IV MelanomaMelanoma (Skin)NCT00098553Alliance for Clinical Trials in Oncology53
已完成
1 期
R115777 in Treating Patients With Advanced Solid TumorsUnspecified Adult Solid Tumor, Protocol SpecificNCT00025454City of Hope Medical Center
已完成
1 期
Chemotherapy in Treating Patients With Breast CancerBreast CancerNCT00012129NYU Langone Health
已完成
1 期
Chemotherapy Given With Amifostine and Filgrastim in Treating Patients With Recurrent or Metastatic CancerUnspecified Adult Solid Tumor, Protocol SpecificLymphomaLeukemiaNCT00003294Roswell Park Cancer Institute24
已完成
1 期
Decitabine in Treating Patients With Melanoma or Other Advanced CancerChronic Myeloproliferative DisordersMultiple Myeloma and Plasma Cell NeoplasmMyelodysplastic SyndromesPrecancerous ConditionUnspecified Adult Solid Tumor, Protocol SpecificLymphomaLeukemiaNCT00002980California Cancer Consortium