A Pilot Study of G-CSF to Disrupt the Bone Marrow Microenvironment in Bortezomib-, Carfilzomib-, or IMID-Refractory Multiple Myeloma
试验速览
- 阶段
- 早期 1 期
- 状态
- 终止
- 入组人数
- 7
- 试验地点
- 1
- 主要终点
- Safety of the combination of G-CSF and bortezomib-, carfilzomib-, or IMID-based treatment regimens in patients with refractory multiple myeloma.
研究概览
简要总结
Based on the pre-clinical data the investigators hypothesize that G-CSF treatment in patients with multiple myeloma will generate a 'hostile' bone marrow microenvironment for myeloma cells, depriving them of key support signals and rendering them more sensitive to chemotherapy. The investigators therefore propose to do an initial pilot study 1) to explore the safety of the combination of G-CSF and bortezomib-, carfilzomib-, or IMID-based treatment regimens in patients with bortezomib-, carfilzomib-, or IMID-refractory myeloma and 2) to generate correlative data for a subsequent larger study looking at the combination.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient must have a confirmed diagnosis of multiple myeloma. The patient may be any stage of multiple myeloma. The patient may have received one or more lines of prior therapy (there is no limit to number of prior lines of therapy permissible).
- •Patient must be ≥18 years of age
- •Patient must be in active treatment with one of the following:
- •twice-weekly bortezomib (on Days 1, 4, 8, and 11 of a 21-day cycle) with or without dexamethasone
- •carfilzomib (on Days 1, 2, 8, 9, 15, and 16 of a 28-day cycle) with or without dexamethasone
- •an IMID with or without dexamethasone daily on Days 1 to
- •Patients being treated with bortezomib or carfilzomb may also be receiving an IMID or PO cyclophosphamide with the regimen.
- •Patient must have shown stable or progressive disease on the current bortezomib-, carfilzomib-, or IMID-containing regimen with a measurable monoclonal protein component in the serum (at least 0.5 g/dl on electrophoresis or 0.05 g/dl [50mg/dl] on serum-free-light-chain). Patients who had an initial response on the current bortezomib-, carfilzomib-, or IMID-containing regimen but now have stable (plateaued) disease are eligible.
- •Patient must have an ECOG performance status of 0 - 2
- •Patient must be receiving concurrent treatment with bisphosphonates, with one dose occurring within 30 days prior to first day (Day -3) of protocol treatment
- •Patient must have acceptable hematologic parameters, defined as:
- •Absolute neutrophil count > 1000 cells/mm3
- •Platelets ≥ 50,000 cells/mm3
- •Hemoglobin ≥ 8 g/dl
- •Patient must have adequate liver function, defined as:
- •Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 3 x upper limit of normal
- •Total bilirubin < 2 x upper limit of normal
- •Patient must be able to understand and willing to sign a written informed consent document
排除标准
- •Patient must not be receiving any agents with known or suspected anti-myeloma activity (other than bortezomib, carfilzomib, dexamethasone, an IMID or PO cyclophosphamide, and bisphosphonates with the current regimen)
- •Patient must not be actively using myeloid growth factors
- •Patient must not have had any prior malignancy, except for adequately treated basal cell or squamous cell skin cancer, in-situ cervical cancer, or other cancer from which the subject has been disease-free for at least 2 years
- •Patient must not have any uncontrolled medical problems such as diabetes mellitus, coronary artery disease, hypertension, unstable angina, arrhythmias, pulmonary disease, and symptomatic heart failure
- •Patient must not have neuropathy ≥ grade 3 or painful neuropathy ≥ grade 2 (NCI CTCAE v 4.0)
- •Patient must not have any known active infections requiring IV antibiotic, antiviral, or antifungal therapy
- •Patient must not be pregnant or breastfeeding
研究组 & 干预措施
Arm 1
Filgrastim 5 ug/kg from Day -3 to Day 10 of a single cycle.
Bortezomib will be given at the patient's current dose on Days 1, 4, 8, and 11 OR Carfilzomib will be given at the patient's current dose on Days 1, 2, 8, 9, 15, and 16 OR IMID will be given at the patient's current dose once daily on Days 1-21. Patients receiving an IMID (thalidomide, lenalidomide, or pomalidomide) as part of a bortezomib or carfilzomb regimen should continue the same scheduled as the current regimen.
Dexamethasone should be continued at the same dose and schedule as the patient's current regimen.
PO cyclophosphamide should be continued at the same dose and schedule as the patient's current regimen.
干预措施: Filgrastim (Drug)
Arm 1
Filgrastim 5 ug/kg from Day -3 to Day 10 of a single cycle.
Bortezomib will be given at the patient's current dose on Days 1, 4, 8, and 11 OR Carfilzomib will be given at the patient's current dose on Days 1, 2, 8, 9, 15, and 16 OR IMID will be given at the patient's current dose once daily on Days 1-21. Patients receiving an IMID (thalidomide, lenalidomide, or pomalidomide) as part of a bortezomib or carfilzomb regimen should continue the same scheduled as the current regimen.
Dexamethasone should be continued at the same dose and schedule as the patient's current regimen.
PO cyclophosphamide should be continued at the same dose and schedule as the patient's current regimen.
干预措施: Bortezomib (Drug)
Arm 1
Filgrastim 5 ug/kg from Day -3 to Day 10 of a single cycle.
Bortezomib will be given at the patient's current dose on Days 1, 4, 8, and 11 OR Carfilzomib will be given at the patient's current dose on Days 1, 2, 8, 9, 15, and 16 OR IMID will be given at the patient's current dose once daily on Days 1-21. Patients receiving an IMID (thalidomide, lenalidomide, or pomalidomide) as part of a bortezomib or carfilzomb regimen should continue the same scheduled as the current regimen.
Dexamethasone should be continued at the same dose and schedule as the patient's current regimen.
PO cyclophosphamide should be continued at the same dose and schedule as the patient's current regimen.
干预措施: Carfilzomib (Drug)
Arm 1
Filgrastim 5 ug/kg from Day -3 to Day 10 of a single cycle.
Bortezomib will be given at the patient's current dose on Days 1, 4, 8, and 11 OR Carfilzomib will be given at the patient's current dose on Days 1, 2, 8, 9, 15, and 16 OR IMID will be given at the patient's current dose once daily on Days 1-21. Patients receiving an IMID (thalidomide, lenalidomide, or pomalidomide) as part of a bortezomib or carfilzomb regimen should continue the same scheduled as the current regimen.
Dexamethasone should be continued at the same dose and schedule as the patient's current regimen.
PO cyclophosphamide should be continued at the same dose and schedule as the patient's current regimen.
干预措施: Dexamethasone (Drug)
Arm 1
Filgrastim 5 ug/kg from Day -3 to Day 10 of a single cycle.
Bortezomib will be given at the patient's current dose on Days 1, 4, 8, and 11 OR Carfilzomib will be given at the patient's current dose on Days 1, 2, 8, 9, 15, and 16 OR IMID will be given at the patient's current dose once daily on Days 1-21. Patients receiving an IMID (thalidomide, lenalidomide, or pomalidomide) as part of a bortezomib or carfilzomb regimen should continue the same scheduled as the current regimen.
Dexamethasone should be continued at the same dose and schedule as the patient's current regimen.
PO cyclophosphamide should be continued at the same dose and schedule as the patient's current regimen.
干预措施: Cyclophosphamide (Drug)
Arm 1
Filgrastim 5 ug/kg from Day -3 to Day 10 of a single cycle.
Bortezomib will be given at the patient's current dose on Days 1, 4, 8, and 11 OR Carfilzomib will be given at the patient's current dose on Days 1, 2, 8, 9, 15, and 16 OR IMID will be given at the patient's current dose once daily on Days 1-21. Patients receiving an IMID (thalidomide, lenalidomide, or pomalidomide) as part of a bortezomib or carfilzomb regimen should continue the same scheduled as the current regimen.
Dexamethasone should be continued at the same dose and schedule as the patient's current regimen.
PO cyclophosphamide should be continued at the same dose and schedule as the patient's current regimen.
干预措施: Thalidomide (Drug)
Arm 1
Filgrastim 5 ug/kg from Day -3 to Day 10 of a single cycle.
Bortezomib will be given at the patient's current dose on Days 1, 4, 8, and 11 OR Carfilzomib will be given at the patient's current dose on Days 1, 2, 8, 9, 15, and 16 OR IMID will be given at the patient's current dose once daily on Days 1-21. Patients receiving an IMID (thalidomide, lenalidomide, or pomalidomide) as part of a bortezomib or carfilzomb regimen should continue the same scheduled as the current regimen.
Dexamethasone should be continued at the same dose and schedule as the patient's current regimen.
PO cyclophosphamide should be continued at the same dose and schedule as the patient's current regimen.
干预措施: Lenalidomide (Drug)
Arm 1
Filgrastim 5 ug/kg from Day -3 to Day 10 of a single cycle.
Bortezomib will be given at the patient's current dose on Days 1, 4, 8, and 11 OR Carfilzomib will be given at the patient's current dose on Days 1, 2, 8, 9, 15, and 16 OR IMID will be given at the patient's current dose once daily on Days 1-21. Patients receiving an IMID (thalidomide, lenalidomide, or pomalidomide) as part of a bortezomib or carfilzomb regimen should continue the same scheduled as the current regimen.
Dexamethasone should be continued at the same dose and schedule as the patient's current regimen.
PO cyclophosphamide should be continued at the same dose and schedule as the patient's current regimen.
干预措施: Pomalidomide (Drug)
结局指标
主要结局
Safety of the combination of G-CSF and bortezomib-, carfilzomib-, or IMID-based treatment regimens in patients with refractory multiple myeloma.
时间窗: Up to 30 days after last treatment
Number and grade of adverse events based on NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
次要结局
- Effects of G-CSF on bone marrow and bone marrow cytokine and chemokine levels. Including: Quantification of marrow osteoblasts and CAR cells, measurement of SDF-1 (CXCL12), IL-6, BAFF, assessment of myeloma cell proliferation and survival in bone marrow(14 days after last drug treatment)
- Response rate as defined by the International Myeloma Working Group (IMWG) criteria(14 days after last drug treatment)
- Overall survival duration of patients treated on study(1 year)
- Progression-free survival of patients treated on study(1 year)
- Duration of response of patients treated on study(1 year)