A Phase II, Trial of Chloroquine in Combination With VELCADE and Cyclophosphamide in Patients With Relapsed and Refractory Myeloma
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 11
- 试验地点
- 1
- 主要终点
- Response Rate (CR + PR After 2 Cycles)
研究概览
简要总结
This pilot phase II trial studies how well giving bortezomib and cyclophosphamide together with chloroquine works in treating patients with relapsed or refractory multiple myeloma.
详细描述
Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Chloroquine may help chemotherapy drugs work better by making cancer cells more sensitive to the drug. Giving bortezomib and cyclophosphamide together with chloroquine may kill more cancer cells.
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
- •Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
- •Female subject is either post-menopausal for at least 1 year before the screening visit, is surgically sterilized or if they are of childbearing potential, agree to practice 2 effective methods of contraception from the time of signing the informed consent form through 30 days after the last dose of VELCADE, or agree to completely abstain from heterosexual intercourse. Male subjects, even if surgically sterilized (ie, status postvasectomy) must agree to 1 of the following: practice effective barrier contraception during the entire study treatment period and through a minimum of 30 days after the last dose of study drug, or completely abstain from heterosexual intercourse.
- •Diagnosis of multiple myeloma based on standard criteria as follows:
- •Major Criteria:
- •I. Plasmacytomas on tissue biopsy
- •II. Bone marrow plasmacytosis (>30% plasma cells)
- •III. Monoclonal immunoglobulin spike on serum electrophoresis (IgG >3.5 G/dL or IgA > 2.0 G/dL) or kappa or lambda light chain excretion> 1 G/day on 24 hour urine protein electrophoresis
- •Minor Criteria
- •Bone marrow plasmacytosis (10 to 30% plasma cells)
- •Monoclonal immunoglobulin present but of lesser magnitude than given under major criteria
- •Lytic bone lesions
- •Normal IgM < 50 mg/dL, IgA < 100 mg/dL, or IgG < 600 mg/dL
- •Any of the following sets of criteria will confirm the diagnosis of Multiple Myeloma:
- •Any two of the major criteria
- •Major criterion I plus minor criterion b, c, or d
- •Major criterion III plus minor criterion a or c
- •Minor criteria a, b and c or a, b and d
- •Measurable disease, defined as a monoclonal immunoglobulin spike on serum electrophoresis of ≥ 1 Gm/dL and/or urine monoclonal immunoglobulin spike of ≥ 200 mg/24 hours.
- •Patients must have refractory myeloma as defined by a greater than 25% increase in their M-protein. They should have progressed on a combination of VELCADE and cyclophosphamide.
- •Non-secretors must have measurable protein by Freelite or measurable disease such as plasmacytoma to be eligible.
- •Karnofsky performance status ≥ 50
- •Patients treated with local radiotherapy with or without a brief exposure to steroids are eligible. Patients who require concurrent radiotherapy should have entry to the protocol deferred until the radiotherapy is completed
- •Meets the following pretreatment laboratory criteria at Baseline (Day 1 of Cycle 1, before study drug administration)
- •Absolute neutrophil count ≥ 0.5 x 10^3/uL
- •Calculated or measured creatinine clearance ≥ 30 mL/min
- •Age 18 years or older
排除标准
- •POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein (M-protein) and skin changes)
- •Plasma cell leukemia
- •Receiving steroids daily for other medical conditions, e.g., asthma, systemic lupus erythematosis, rheumatoid arthritis
- •Infection not controlled by antibiotics
- •HIV infection. Patients should provide consent for HIV testing according to the institution's standard practice
- •Known active hepatitis B or C
- •Patient had myocardial infarction within 6 months prior to enrollment, New York Hospital Association (NYHA) Class III or IV heart failure, (see appendix D), uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at screening must be documented by the investigator as not medically relevant.
- •Diagnosed or treated for another malignancy within 3 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy.
- •Radiation therapy within 3 weeks before randomization. Enrollment of subjects who require concurrent radiotherapy (which must be localized in its field size) should be deferred until the radiotherapy is completed and 3 weeks have elapsed since the last date of therapy.
- •Other serious medical or psychiatric illness that could potentially interfere with the completion of treatment according to this protocol
- •Female subject is pregnant or lactating. Confirmation that the subject is not pregnant must be established by a negative serum B-human chorionic gonadotropin (B hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for postmenopausal or surgically sterilized women.
- •Patient has > Grade 2 peripheral neuropathy
- •Patient has known hypersensitivity to VELCADE, boron or mannitol, quinidine or quinidine derivatives or to cyclophosphamide or any component of the formulation.
- •Participation in clinical trials with other investigational agents not included in this trial, within 14 days of the start of this trial and throughout the duration of this trial.
- •Patients with preexisting retinal or visual field changes.
- •Patient has > 1.5 x upper limit of normal Total Bilirubin
研究组 & 干预措施
Velcade+Cyclophosphamide+Chloroquine
VELCADE given by intravenous push at 1.3 mg/m^2 on days 1, 4, 8, 11, 22, 25, 29 and 32.
Cyclophosphamide given at 50 mg orally twice per day on days 1-14 and 22-35.
Chloroquine given at 500 mg orally daily on days 1-14 and 22-35.
Each cycle is 42 days in length.
干预措施: Velcade (Drug)
Velcade+Cyclophosphamide+Chloroquine
VELCADE given by intravenous push at 1.3 mg/m^2 on days 1, 4, 8, 11, 22, 25, 29 and 32.
Cyclophosphamide given at 50 mg orally twice per day on days 1-14 and 22-35.
Chloroquine given at 500 mg orally daily on days 1-14 and 22-35.
Each cycle is 42 days in length.
干预措施: Cyclophosphamide (Drug)
Velcade+Cyclophosphamide+Chloroquine
VELCADE given by intravenous push at 1.3 mg/m^2 on days 1, 4, 8, 11, 22, 25, 29 and 32.
Cyclophosphamide given at 50 mg orally twice per day on days 1-14 and 22-35.
Chloroquine given at 500 mg orally daily on days 1-14 and 22-35.
Each cycle is 42 days in length.
干预措施: Chloroquine (Drug)
结局指标
主要结局
Response Rate (CR + PR After 2 Cycles)
时间窗: Up to 2 years
Response rate is defined as the percentage of patients who have a complete response (CR) or partial response (PR). Responses were assessed every two cycles of treatment, based on the criteria published by the International Myeloma Working Group (Durie, et al, 2006). Per International Myeloma Working Group response criteria: CR: Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and \< 5% plasma cells in bone marrow PR: \> 50% reduction of serum M-protein and reduction in 24 hours urinary M-protein by \>90% or to \< 200 mg/24 h
次要结局
- Percentage of Subjects Who Have Complete Response or Partial Response and Have 2+ or Higher Autophagy(until clinical response (up to 2 years))
- Number of Participants With Adverse Events of Grade 3 or Higher(Treatment period plus 30 days post-treatment)
- Median Duration of Response of This Regimen(up to 2 years)