Phase III Randomized Trial of Thalidomide/Dexamethasone vs VAD as Induction Chemotherapy for Newly Diagnosed Myeloma Patients and Evaluation of the Effects of Zoledronate on Chemotherapy Induced Apoptosis and Antigen Presentation.
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 90
- 试验地点
- 5
- 主要终点
- Response Rates of VAD vs. Thalidomide/Dexamethasone
研究概览
简要总结
Investigators planned to accrue 176 participants, to compare the response rate, overall response rate and survival of patients with multiple myeloma (MM) when randomized to two regimens (thalidomide+Dexamethasone versus Vincristine+Adriamycin+Dexamethasone). Investigators also planned to test if treatment with zoledronate immediately prior to chemotherapy results in an enhanced response to treatment (i.e. increase in complete response rates).
详细描述
Patients Randomized to receive VAD (vincristine, adriamycin, dexamethasone): All patients received four cycles of VAD repeated every 4 weeks. Chemotherapy was administered by continuous IV Infusion for 96 hours: vincristine at a dose of 0.4 mg/day and doxorubicin at a dose of 9 mg/m^2/day. Patients were administered dexamethasone 40 mg by mouth (PO) on days 1 to 4, 9 to 12, and 17 to 20 of the initial two cycles. Dexamethasone was given only on days 1-4 of all subsequent cycles. Patients were randomized to receive zoledronic acid IV on either Day 1 or 15 of each cycle. This schedule continued monthly as long as the patient remained on study. The dose was calculated based on the patients' monthly creatinine clearance. Upon initiation of Zometa therapy, the following guidelines were applied: For patients with creatinine clearance >60 mL/min, the recommended dose remained at 4mg. For patients with reduced creatinine clearance, dosing was calculated to achieve the same area under curve (AUC) as in patients with creatinine clearance of 75 mL/min. Creatinine clearance was calculated using the Cockcroft-Gault formula.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •Patients must have newly diagnosed MM confirmed by the presence of bone marrow plasmacytosis with > 10 percent plasma cells, sheets of plasma cells, or biopsy-proven plasmacytoma. Patients must have Durie-Salmon Stage IIA-B or IIIA-B. Patients with non-secretory myeloma are eligible. (These patients will not be included in the analysis of response rates, but will be assessed for toxicity and survival).
- •Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, 2, or 3
- •≥ 18 years of age.
- •Signed informed consent form
- •Expected survival of greater than 8 weeks
- •Capable of swallowing study medication tablets
- •Capable of following directions regarding taking study medication, or has a daily care provider who will be responsible for administering study medication.
- •Patients will be eligible for study even if they lack socioeconomic access to autologous transplantation. (These patients will be identified prior to randomization so as not to confound study results).
- •All patients (in the event that they are randomized to the thalidomide/dexamethasone arm) must agree to take part in the "System for Education and Prescribing Safety" (S.T.E.P.S.)™. They must sign a separate informed consent for this program.
排除标准
- •Elevated direct bilirubin > 2 mg/dl
- •Serum alanine aminotransferase (ALT) or serum aspartate aminotransferase (AST) > 2 times the upper limit of normal (ULN)
- •Absolute neutrophil count (ANC) <1000/mL, unless felt to be secondary to myeloma
- •Ongoing radiation therapy, or radiation therapy within 3 weeks prior to first treatment, unless the acute side effects associated with such therapy are resolved.
- •Prior treatment for multiple myeloma
- •Prior bisphosphonate use is allowed but they must be discontinued before starting treatment.
- •Concurrent uncontrolled serious infection
- •Patients with peripheral (sensory) neuropathy, grade 3 or higher
- •Life-threatening illness (unrelated to tumor)
- •History of any other ACTIVE and INVASIVE cancer other than the present condition (except non-melanoma skin cancer), unless in complete remission and off of all therapy for that disease for a minimum of 3 years.
- •Women of childbearing potential (unless utilizing birth control) or who are pregnant or nursing will be excluded from this study.
- •Patients with comorbid conditions that would contraindicate the use of vincristine, doxorubicin, dexamethasone, thalidomide, or zoledronate.
- •Plasma Cell Leukemia
研究组 & 干预措施
VAD Treatment
VAD (vincristine, adriamycin, dexamethasone). Vincristine and adriamycin was administered by continuous infusion via a venous catheter for 96 hours every 28 days. Each 28 days is considered one "cycle" of therapy. Patients were to receive 4 to 6 cycles of therapy. Dexamethasone was taken in pill form. During the first 2 cycles it was taken on days 1-4, 9-12, 17-20. For all other cycles dexamethasone was taken only on days 1-4. Patients were randomized to receive zoledronic acid IV on either Day 1 or 15 of each cycle.
干预措施: zoledronic acid (Drug)
VAD Treatment
VAD (vincristine, adriamycin, dexamethasone). Vincristine and adriamycin was administered by continuous infusion via a venous catheter for 96 hours every 28 days. Each 28 days is considered one "cycle" of therapy. Patients were to receive 4 to 6 cycles of therapy. Dexamethasone was taken in pill form. During the first 2 cycles it was taken on days 1-4, 9-12, 17-20. For all other cycles dexamethasone was taken only on days 1-4. Patients were randomized to receive zoledronic acid IV on either Day 1 or 15 of each cycle.
干预措施: vincristine (Drug)
VAD Treatment
VAD (vincristine, adriamycin, dexamethasone). Vincristine and adriamycin was administered by continuous infusion via a venous catheter for 96 hours every 28 days. Each 28 days is considered one "cycle" of therapy. Patients were to receive 4 to 6 cycles of therapy. Dexamethasone was taken in pill form. During the first 2 cycles it was taken on days 1-4, 9-12, 17-20. For all other cycles dexamethasone was taken only on days 1-4. Patients were randomized to receive zoledronic acid IV on either Day 1 or 15 of each cycle.
干预措施: adriamycin (Drug)
Thalidomide and Dexamethasone Treatment
Thalidomide was taken orally once every day in the evening for four to six months. The dexamethasone was taken in a pill form. During the first 2 cycles it was taken on days 1-4, 9-12, 17-20. For all other cycles dexamethasone was taken only on days 1-4.
干预措施: zoledronic acid (Drug)
Thalidomide and Dexamethasone Treatment
Thalidomide was taken orally once every day in the evening for four to six months. The dexamethasone was taken in a pill form. During the first 2 cycles it was taken on days 1-4, 9-12, 17-20. For all other cycles dexamethasone was taken only on days 1-4.
干预措施: dexamethasone (Drug)
Thalidomide and Dexamethasone Treatment
Thalidomide was taken orally once every day in the evening for four to six months. The dexamethasone was taken in a pill form. During the first 2 cycles it was taken on days 1-4, 9-12, 17-20. For all other cycles dexamethasone was taken only on days 1-4.
干预措施: thalidomide (Drug)
结局指标
主要结局
Response Rates of VAD vs. Thalidomide/Dexamethasone
时间窗: End of Cycle 4 - 4 Months per Participant
Blade (15) criteria for remission in multiple myeloma was used to assess response. Complete Response (CR)includes: Disappearance of the original monoclonal protein from the blood and urine on at least two determinations for a minimum of 6 weeks by immunofixation studies. Partial Response (PR) includes: At least a 50% reduction in the level of serum monoclonal protein for at least two determinations 6 weeks apart. Minimal Response (MR)includes: At least a 25% to 49% reduction in the level of serum monoclonal protein for at least 2 determinations 2 weeks apart.
次要结局
- Number of Participants With Adverse Events, by Group(4 Years, 7 Months)
- Number of Participants With Progression Free Survival (PFS), by Treatment Arm(4 Months)
- Overall Survival (OS), by Treatment Arm(Up to 10 Years)