NCT00006021已完成1 期
Phase I/II Trial of Arsenic Trioxide (As2O3) With Ascorbic Acid in the Treatment of Relapsed/Refractory Multiple Myeloma
适应症
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 22
- 试验地点
- 4
- 主要终点
- Disease response as measured by M protein quantitation and the percentage of plasma cell infiltration in bone marrow biopsies after every course
研究概览
简要总结
RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Vitamin C may increase the effectiveness of arsenic trioxide by making cancer cells more sensitive to the drug.
PURPOSE: Phase I/II trial to determine the effectiveness of arsenic trioxide plus vitamin C in treating patients who have recurrent or refractory multiple myeloma.
详细描述
OBJECTIVES:
- Determine the maximum tolerated dose of arsenic trioxide when administered with ascorbic acid in patients with recurrent or refractory multiple myeloma.
- Determine the therapeutic efficacy of this treatment combination in these patients.
- Determine the expression of MDR and Bcl-xL genes and the intracellular levels of GSH in these patients before and after this treatment regimen and assess whether these measures have prognostic value.
OUTLINE: This is a multicenter, dose-escalation study of arsenic trioxide.
- Phase I: Patients receive arsenic trioxide IV over 1-4 hours and ascorbic acid IV over 5-10 minutes on days 1-5 weekly for 5 weeks. Treatment continues every 7 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of arsenic trioxide until the maximum tolerated dose (MTD) is reached. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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 120 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •DISEASE CHARACTERISTICS:
- •Histologically confirmed multiple myeloma
- •M-protein by serum protein electrophoresis or urine protein electrophoresis
- •Quantitative determination of immunoglobulin
- •Bone marrow biopsy and aspirate with a plasma cell count greater than 10%
- •Refractory or chemoresistant disease defined as failure to respond (less than 50% reduction in M protein level) or progression within 2 months after receiving at least 2 chemotherapy regimens including:
- •Alkylating based regimen (melphalan) in combination with steroids (prednisone) or other chemotherapy regimens (e.g., vincristine, bleomycin, melphalan, cyclophosphamide, and prednisone or vincristine, carmustine, doxorubicin, and prednisone)
- •Vincristine, doxorubicin, and dexamethasone (VAD) regimen
- •Pulse therapy with high dose steroids alone
- •High dose alkylating agent and autologous stem cell transplantation
- •Allogeneic bone marrow transplantation
- •Plateau phase defined as M protein in the serum or urine for more than 6 weeks despite response to prior therapy
- •Must have received at least 2 of the chemotherapy regimens listed above or equivalent regimens
- •Recurrent disease defined as progression more than 2 months after initial therapy and failure to respond (less than 50% reduction or progression in M protein levels) to 1 chemotherapy regimen listed above or other salvage regimens (e.g., high-dose cyclophosphamide or topotecan)
- •Must have received VAD or other equivalent chemotherapy regimen
- •Should be considered for autologous or allogenic transplantation
- •Prior local radiotherapy allowed
- •PATIENT CHARACTERISTICS:
- •Performance status:
- •Karnofsky 60-100%
- •Life expectancy:
- •Not specified
- •Hematopoietic:
- •WBC at least 2,000/mm^3*
- •Platelet count at least 50,000/mm^3* NOTE: *Unless attributable to bone marrow infiltration by multiple myeloma
- •Bilirubin less than 3 mg/dL
- •Transaminases less than 2.5 times upper limit of normal (ULN)
- •Creatinine less than 1.5 times ULN OR
- •Creatinine clearance at least 60 mL/min
- •Cardiovascular:
- •No cardiac arrhythmias including recurrent supraventricular arrhythmia, any type of sustained ventricular arrhythmia, or conduction block (atrioventricular block grade II or III, left bundle branch block)
- •Ejection fraction at least 30%
- •No uncontrolled ischemic heart disease
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective barrier contraception during and for 4 months after study
- •HIV negative
- •No grade 3 or higher neurological disorder, including seizure disorders
- •No underlying medical condition that would preclude study
- •No other active malignancy except adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix
- •PRIOR CONCURRENT THERAPY:
- •Biologic therapy:
- •See Disease Characteristics
- •Chemotherapy:
- •See Disease Characteristics
- •At least 2 weeks since prior chemotherapy
- •Endocrine therapy:
- •See Disease Characteristics
- •Concurrent steroid treatment allowed except for primary treatment of myeloma
- •Radiotherapy:
- 另有 6 项未显示
排除标准
- 未提供
结局指标
主要结局
Disease response as measured by M protein quantitation and the percentage of plasma cell infiltration in bone marrow biopsies after every course
次要结局
- Toxicity as measured by CTCAE criteria
研究者
研究点 (4)
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