Clarithromycin Plus CTd (Cyclophosphamide,Thalidomide and Dexamethasone)Regimen for Patients With Newly Diagnosed Multiple Myeloma:a Phase 3 , Multicenter,Randomized, Open-Label Trial.
试验速览
- 阶段
- 3 期
- 发起方
- 入组人数
- 130
- 试验地点
- 1
- 主要终点
- Percentage of Participants With Very Good Partial Remission (VGPR) or Better
研究概览
简要总结
Due to economic reasons, thalidomide is still widely used as a first line drug for Multiple Myeloma patients in China. However,the efficacy of CTd is still lower than the therapeutic regimens with new drugs. Clarithromycin may have partly efficacy in association with steroids and thalidomide for Multiple Myeloma patients. This multicenter, randomized, phase 3 clinical trial is proposed to explore whether clarithromycin could potentiate responsiveness of CTd (Cyclophosphamide, Thalidomide and Dexamethasone) regimen in Newly Diagnosed Multiple Myeloma patients. The trial will also evaluate the side effects caused by the combination of these drugs.
详细描述
This phase III,randomized controlled trial will enroll 130(65 each arm) newly diagnosed patients with active disease from 4 medical centers in East China.
The participants are randomly equally selected to receive BiCTd regimen arm or CTd regimen arm. The treatment consists of eight induction and consolidation therapy followed by maintenance therapy.
BiCTd(Clarithromycin, Cyclophosphamide, Thalidomide and Dexamethasone) regimen arm：
Induction and consolidation Phase:
All patients will also receive aspirin 100mg PO QD while receiving BiCTd. Aspirin will continue through maintenance.
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
- •Signed informed consent form
- •Able to adhere to the study visit schedule and other protocol requirements
- •Diagnosed with active multiple myeloma
- •Previously untreated
- •Karnofsky performance status(KPS) ≥50（KPS<50 will be allowed if related to bony disease）
- •New York Heart Association(NYHA) functional ≤class III
排除标准
- •Hypersensitivity to clarithromycin or any of its excipients, erythromycin, or any of the macrolide antibiotics;
- •Concomitant administration of cisapride, pimozide, astemizole, terfenadine, ergotamine or dihydroergotamine, simvastatin, lovastatin, and atorvastatin;
- •A history of cholestatic jaundice/hepatic dysfunction associated with prior use of clarithromycin.
- •Impaired renal function,Creatinine ≥221umol/L；
- •Pregnant or breast feeding females.
- •Any condition which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.
研究组 & 干预措施
BiCTd regimen
Induction and consolidation therapy: BiCTd regimen for 8 cycles. Patients received Clarithromycin 500 mg orally on days 1-28,thalidomide 100-200mg orally on days d1-28, dexamethasone 40mg orally on days on 1,8,15,22, and cyclophosphamide 300mg/m^2 intravenously on day 1-3. Cycles were repeated every 28 days.
Maintenance therapy:CP regimen (cyclophosphamide 200 mg orally on days 1-14 and prednisone 30mg twice daily orally on days 1-7,repeated every 28 days) until disease progression.
If efficacy <PR after 4 cycles of induction or disease progression at anytime，patients will be quitted.
干预措施: Clarithromycin (Drug)
BiCTd regimen
Induction and consolidation therapy: BiCTd regimen for 8 cycles. Patients received Clarithromycin 500 mg orally on days 1-28,thalidomide 100-200mg orally on days d1-28, dexamethasone 40mg orally on days on 1,8,15,22, and cyclophosphamide 300mg/m^2 intravenously on day 1-3. Cycles were repeated every 28 days.
Maintenance therapy:CP regimen (cyclophosphamide 200 mg orally on days 1-14 and prednisone 30mg twice daily orally on days 1-7,repeated every 28 days) until disease progression.
If efficacy <PR after 4 cycles of induction or disease progression at anytime，patients will be quitted.
干预措施: Thalidomide (Drug)
BiCTd regimen
Induction and consolidation therapy: BiCTd regimen for 8 cycles. Patients received Clarithromycin 500 mg orally on days 1-28,thalidomide 100-200mg orally on days d1-28, dexamethasone 40mg orally on days on 1,8,15,22, and cyclophosphamide 300mg/m^2 intravenously on day 1-3. Cycles were repeated every 28 days.
Maintenance therapy:CP regimen (cyclophosphamide 200 mg orally on days 1-14 and prednisone 30mg twice daily orally on days 1-7,repeated every 28 days) until disease progression.
If efficacy <PR after 4 cycles of induction or disease progression at anytime，patients will be quitted.
干预措施: Cyclophosphamide (Drug)
BiCTd regimen
Induction and consolidation therapy: BiCTd regimen for 8 cycles. Patients received Clarithromycin 500 mg orally on days 1-28,thalidomide 100-200mg orally on days d1-28, dexamethasone 40mg orally on days on 1,8,15,22, and cyclophosphamide 300mg/m^2 intravenously on day 1-3. Cycles were repeated every 28 days.
Maintenance therapy:CP regimen (cyclophosphamide 200 mg orally on days 1-14 and prednisone 30mg twice daily orally on days 1-7,repeated every 28 days) until disease progression.
If efficacy <PR after 4 cycles of induction or disease progression at anytime，patients will be quitted.
干预措施: Dexamethasone (Drug)
CTd regimen
Induction and consolidation therapy: CTd regimen for 8 cycles. Patients received thalidomide 100-200mg orally on days d1-28, dexamethasone 40 mg orally on days on 1,8,15,22, and cyclophosphamide 300 mg/m^2 intravenously on day 1-3. Cycles were repeated every 28 days.
Maintenance therapy:CP regimen (cyclophosphamide 200 mg orally on days 1-14 and prednisone 30mg twice daily orally on days 1-7,28 Days per Cycle) until disease progression.
If efficacy <PR after 4 cycles of induction or disease progression at anytime，patients will be quitted.
If no further reduction in the serum and urine M protein in the next cycle，patients may cross over to BiCTd regimen.
干预措施: Thalidomide (Drug)
CTd regimen
Induction and consolidation therapy: CTd regimen for 8 cycles. Patients received thalidomide 100-200mg orally on days d1-28, dexamethasone 40 mg orally on days on 1,8,15,22, and cyclophosphamide 300 mg/m^2 intravenously on day 1-3. Cycles were repeated every 28 days.
Maintenance therapy:CP regimen (cyclophosphamide 200 mg orally on days 1-14 and prednisone 30mg twice daily orally on days 1-7,28 Days per Cycle) until disease progression.
If efficacy <PR after 4 cycles of induction or disease progression at anytime，patients will be quitted.
If no further reduction in the serum and urine M protein in the next cycle，patients may cross over to BiCTd regimen.
干预措施: Cyclophosphamide (Drug)
CTd regimen
Induction and consolidation therapy: CTd regimen for 8 cycles. Patients received thalidomide 100-200mg orally on days d1-28, dexamethasone 40 mg orally on days on 1,8,15,22, and cyclophosphamide 300 mg/m^2 intravenously on day 1-3. Cycles were repeated every 28 days.
Maintenance therapy:CP regimen (cyclophosphamide 200 mg orally on days 1-14 and prednisone 30mg twice daily orally on days 1-7,28 Days per Cycle) until disease progression.
If efficacy <PR after 4 cycles of induction or disease progression at anytime，patients will be quitted.
If no further reduction in the serum and urine M protein in the next cycle，patients may cross over to BiCTd regimen.
干预措施: Dexamethasone (Drug)
结局指标
主要结局
Percentage of Participants With Very Good Partial Remission (VGPR) or Better
时间窗: up to 4 months
Quality of response: % Complete Response (CR) + Very Good Partial Remission (VGPR) to induction BiCTd or CTd as assessed using International Myeloma Working Group Response Definitions. Very Good Partial Remission (VGPR): Detectable serum and urine M component on immunofixation but not on electrophoresis or 90% or greater reduction in serum M protein with less than 100 mg/24 h of urinary M protein. Complete Remission (CR): The presence of less than 5% bone marrow plasmacytosis and the disappearance of all evidence of serum and urine M-components on electrophoresis as well as by immunofixation. In addition, soft tissue plasmacytoma must have disappeared.
次要结局
- Number of participants with adverse events(up to 48 months)
- 2 Year Overall Survival (OS) Rate(up to 24 months)
- Median Progression Free Survival (PFS) in months(From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 Months)
研究者
Yongping Zhai
Department of hemotology
Jinling Hospital, China