Primary Treatment of Waldenstrom's Macroglobulinemia With Bortezomib (Velcade) and Rituximab (Rituxan) Followed by Autologous Stem Cell Collection
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 46
- 试验地点
- 1
- 主要终点
- Response Rate After 2 Cycles of Treatment With Bortezomib and Rituximab
研究概览
简要总结
The main goal of this clinical research study is to learn if Velcade ® (bortezomib) given with rituximab can help to control WM. This drug combination will allow researchers to collect your stem cells in case it is possible to transplant the stem cells as treatment if your WM gets worse. Researchers will also look at the safety and tolerability of this drug combination followed by treatment with other drug combinations.
详细描述
Bortezomib is designed to block a protein that plays a role in cell function and growth, which may cause cancer cells to die.
Rituximab is designed to attach to cancer cells, which may cause them to die.
Cyclophosphamide, vincristine, doxorubicin, and cladribine are designed to interfere with the multiplication of cancer cells, which may slow or stop their growth and spread throughout the body. This may cause the cancer cells to die.
Dexamethasone is designed to decrease inflammation. It is also used to treat certain forms of cancer.
Before you can start treatment on this study, you will have "screening tests." These tests will help the doctor decide if you are eligible to take part in this study. The tests may be performed within 28 days of starting the study drug. You will have a physical exam, including measurement of vital signs (blood pressure, heart rate, temperature, and breathing rate), height, and weight. Your medical history will be recorded. You will be asked to fill out a questionnaire regarding any neuropathy (nerve problems) you may have. The questionnaire will take about 1 minute to complete. You will have an electrocardiogram (ECG -- a test that measures the electrical activity of the heart). You will also have blood (about 4-5 teaspoons) drawn one time and urine collected (over 24 hours) to check the status of your WM. This blood is also used to screen for hepatitis. You will have an x-ray of your chest. You will have computed tomography (CT) scans of your abdomen and pelvis to see which part of your body is involved with WM. If your chest x-ray is positive, you will also have a CT scan of your chest. Women who are able to have children must have a negative blood (about 2 teaspoons) or urine pregnancy test before starting the study. You will also have a bone marrow aspiration and biopsy. To collect a bone marrow aspirate/biopsy, an area of the hip bone will be made numb with an anesthetic, and a small amount of bone marrow and bone will be withdrawn through a large needle.
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
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with symptomatic macroglobulinemic lymphoma who have had no prior treatment, or whose prior treatment has been limited to steroids and/or alpha-interferon, are eligible. Macroglobulinemic lymphoma includes patients with either biopsy proven clonal lymphocytic or lymphoplasmacytic proliferation and monoclonal IgM. Also included are symptomatic patients with clonal proliferation producing a pathologic monoclonal IgM that causes cryoglobulinemia, peripheral neuropathy or cold agglutinin hemolytic anemia.
- •Patients must have acceptable liver function (total bilirubin < 2.5mg/dL) and renal function (creatinine < 2.0mg/dL). Patients with impaired renal function will only be included if the renal failure is secondary to macroglobulinemic lymphoma (i.e. Bence Jones proteinuria, cryoglobulinemia, ureteral obstruction due to mass) that might reverse with improvement of disease.
- •Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study.
- •Male subject agrees to use an acceptable method for contraception for the duration of the study.
- •Patients must voluntarily sign an informed consent form indicating that they are aware of the investigational nature of the study, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future care.
- •Patient has a heart rate (HR) of greater than or equal to 50 bpm.
排除标准
- •Patient has a platelet count of <30x10^9/L within 28 days before enrollment unless due to >/= 75% marrow infiltration by macroglobulinemic lymphoma or splenomegaly.
- •Patient has an absolute neutrophil count of <1.0x10^9/L within 28 days before enrollment unless due to >/= 75% marrow infiltration by macroglobulinemic lymphoma.
- •Patient has a calculated or measured creatinine >/= to 2.0mg/dL on baseline evaluation. Patients with impaired renal function will only be included if the renal failure is secondary to macroglobulinemic lymphoma (i.e. Bence Jones proteinuria, cryoglobulinemia, ureteral obstruction due to mass).
- •Patient has >/= Grade 2 peripheral neuropathy on baseline evaluation.
- •Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure, 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 has to be documented by the investigator as not medically relevant.
- •Patient has hypersensitivity to boron, mannitol, or murine proteins.
- •Female subject is pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum or urine Beta -human chorionic gonadotropin (B-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women.
- •Patient has received other investigational drugs within 14 days before enrollment
- •Patient has a serious medical or psychiatric illness that is likely to interfere with participation in this clinical study.
- •Eastern Cooperative Oncology Group (ECOG) performance status of >
- •Patient with a "currently active" second malignancy, other than non-melanoma skin cancer and carcinoma in situ of the cervix, should not be enrolled. Patients are not considered to have a "currently active" malignancy if they have completed therapy for a prior malignancy, are disease free from prior malignancies for > 5 years and are considered by their physician to be at less than 30 % risk of relapse.
- •Patient with a lifetime cumulative dose of > 450 mg/m^2 of anthracyclines.
- •Patients with an active hepatitis B infection.
研究组 & 干预措施
Bortezomib + Rituximab
Bortezomib 1.6 mg/m^2 IV Weekly on Days 1, 8, 15 and 22. Rituximab 375 mg/m^2 IV on Day 8 and 22. Valacyclovir 500 mg orally daily (or acyclovir 200 mg orally twice daily).
干预措施: Bortezomib (Drug)
Bortezomib + Rituximab
Bortezomib 1.6 mg/m^2 IV Weekly on Days 1, 8, 15 and 22. Rituximab 375 mg/m^2 IV on Day 8 and 22. Valacyclovir 500 mg orally daily (or acyclovir 200 mg orally twice daily).
干预措施: Rituximab (Drug)
Bortezomib + Rituximab
Bortezomib 1.6 mg/m^2 IV Weekly on Days 1, 8, 15 and 22. Rituximab 375 mg/m^2 IV on Day 8 and 22. Valacyclovir 500 mg orally daily (or acyclovir 200 mg orally twice daily).
干预措施: Valacyclovir (Drug)
结局指标
主要结局
Response Rate After 2 Cycles of Treatment With Bortezomib and Rituximab
时间窗: After 2 (35 day) cycles of treatment
Partial response (PR) defined as at least \> 50 % reduction of serum monoclonal IgM concentration determined by protein electrophoresis, \> 50% decrease in adenopathy / organomegaly on physical examination or on CT scan, and no new symptoms or signs of active disease. Complete response (CR) defined as a disappearance of serum and urine monoclonal protein determined by immunofixation, absence of malignant cells in bone marrow determined by histologic evaluation, resolution of adenopathy/organomegaly (confirmed by computed tomography \[CT\] scan), and no signs or symptoms attributable to WM. Stable disease defined as neither grown nor shrunk; the amount of disease has not changed.Participants will be followed for \< 6 months after receiving bortezomib/rituximab or rituximab-modified hyper-CVAD to be considered unresponsive to therapy in accordance with the guidelines of the Consensus Panel of the Third International Workshop on Waldenstrom's Macroglobulinemia.
Response Rate After 3 Cycles of Treatment With Bortezomib and Rituximab
时间窗: After 3 (35 day) cycles of treatment
Partial response (PR) defined as at least \> 50 % reduction of serum monoclonal IgM concentration determined by protein electrophoresis, \> 50% decrease in adenopathy / organomegaly on physical examination or on CT scan, and no new symptoms or signs of active disease. Complete response (CR) defined as a disappearance of serum and urine monoclonal protein determined by immunofixation, absence of malignant cells in bone marrow determined by histologic evaluation, resolution of adenopathy/organomegaly (confirmed by computed tomography \[CT\] scan), and no signs or symptoms attributable to WM. Stable disease defined as neither grown nor shrunk; the amount of disease has not changed. Participants will be followed for \< 6 months after receiving bortezomib/rituximab or rituximab-modified hyper-CVAD to be considered unresponsive to therapy in accordance with the guidelines of the Consensus Panel of the Third International Workshop on Waldenstrom's Macroglobulinemia.
Participants Ability to Collect Stem Cells After Treatment With Bortezomib and Rituximab
时间窗: 4 weeks
Number of Participants who were able to collect stem cells successfully or unable to collect after treatment with bortezomib and rituximab.
次要结局
未报告次要终点