Phase III-study for Evaluation of Induction Therapy Before Stem Cell Mobilization and Tandem High-dose Melphalan in Multiple Myeloma Patients 60 to 70 Years of Age
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 549
- 主要终点
- Event free survival
研究概览
简要总结
Patients 60 to 70 years of age with newly diagnosed multiple myeloma were prospectively randomized between 4 cycles of anthracycline/dexamethasone-based induction chemotherapy (A1) or only 2 x 4 days of dexamethasone (A2). A reference arm included patients who could not be randomized (B). Tandem melphalan 140 mg/m² (MEL140) with autologous transplantation was scheduled for all patients.
详细描述
In arm A1, patients received 4 cycles of conventional induction therapy with anthracycline/dexamethasone-based regimens. Specified in the protocol were vincristine/doxorubicin/dexamethasone (VAD), idarubicin/dexamethasone (ID) and cyclophosphamide/doxorubicin/dexamethasone (CAD). In arm A2, patients were planned to receive only dexamethasone 40 mg orally on days 1-4 and 8-11 for symptom control before stem cell mobilization. For the patients in arm B, a maximum of 6 cycles of induction chemotherapy was allowed. Following this, the treatment was identical for all patients. For stem cell mobilization, an age-adjusted IEV-regimen with granulocyte-colony stimulating factor (G-CSF) was recommended. The target dose for stem cell collection was 6 x 10E+6 CD34 (cluster of differentiation 34)-positive cells/kg (2 transplants and one back-up). The standard dose for each transplantation was 2 x 10E+6 CD34-positive cells/kg. High-dose melphalan at a total dose of 140 mg/m² (MEL140) was given in two doses of 70 mg/m² on days -3 and -2. Stem cell transplantation (SCT) was performed on day 0. A second MEL140 course was planned two months after the first. Regular bisphosphonate treatment was recommended.
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
- 60 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histological confirmed multiple myeloma stage II or III according to the classification of Salmon and Durie
- •Aged between 60 and 70 years
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- •Signed and dated written informed consent
- •No previous chemotherapy or not more than one cycle in total or previous chemotherapy of more than one cycle if paused for at least 6 months and not more than six cycles in total (arm A1 and A2 only)
- •Ongoing primary chemotherapy of two to maximum six cycles (arm B only)
排除标准
- •Multiple myeloma stage I according to the classification of Salmon and Durie without need of any therapy
- •Aged under 60 or over 70 years
- •ECOG performance status >2
- •Previous chemotherapy of more than six cycles
- •Informed consent missing
- •Myocardial infarction within the last six months
- •Cardiac dysrhythmia stage IV b according to the classification of Lown
- •Heart failure >NYHA II according to the classification of the New York Heart Association (NYHA), left ventricular ejection fraction <50% in ECG
- •Severe restrictive or obstructive pulmonary disease (diffusing capacity <60% under normal)
- •Renal insufficiency including a serum creatinine level >2mg/dl if not caused by multiple myeloma and reversible
- •Liver diseases combined with an elevation of transaminases and of bilirubin of three times above normal
- •Severe infections (HIV, hepatitis B/C, syphilis etc. )
- •Severe psychiatric disease
- •Other not curative treated malignant tumor within the last five years
- •Concurrent participation in other clinical studies
- •Other not curative treated malignant tumor within the last five years
研究组 & 干预措施
A1: Induction chemotherapy
Anthracycline/dexamethasone-based induction chemotherapy Tumor-reduction chemotherapy and stem cell mobilization Stem cell apheresis Tandem high-dose chemotherapy Autologous peripheral blood stem cell transplantation
干预措施: Anthracycline/dexamethasone-based induction chemotherapy (Drug)
A1: Induction chemotherapy
Anthracycline/dexamethasone-based induction chemotherapy Tumor-reduction chemotherapy and stem cell mobilization Stem cell apheresis Tandem high-dose chemotherapy Autologous peripheral blood stem cell transplantation
干预措施: Tumor-reduction chemotherapy and stem cell mobilization (Drug)
A1: Induction chemotherapy
Anthracycline/dexamethasone-based induction chemotherapy Tumor-reduction chemotherapy and stem cell mobilization Stem cell apheresis Tandem high-dose chemotherapy Autologous peripheral blood stem cell transplantation
干预措施: Stem cell apheresis (Procedure)
A1: Induction chemotherapy
Anthracycline/dexamethasone-based induction chemotherapy Tumor-reduction chemotherapy and stem cell mobilization Stem cell apheresis Tandem high-dose chemotherapy Autologous peripheral blood stem cell transplantation
干预措施: Tandem high-dose chemotherapy (melphalan) (Drug)
A1: Induction chemotherapy
Anthracycline/dexamethasone-based induction chemotherapy Tumor-reduction chemotherapy and stem cell mobilization Stem cell apheresis Tandem high-dose chemotherapy Autologous peripheral blood stem cell transplantation
干预措施: Autologous peripheral blood stem cell transplantation (Procedure)
A2: No induction chemotherapy
Dexamethasone for control of symptoms Tumor-reduction chemotherapy and stem cell mobilization Stem cell apheresis Tandem high-dose chemotherapy Autologous peripheral blood stem cell transplantation
干预措施: Dexamethasone for control of symptoms (Drug)
A2: No induction chemotherapy
Dexamethasone for control of symptoms Tumor-reduction chemotherapy and stem cell mobilization Stem cell apheresis Tandem high-dose chemotherapy Autologous peripheral blood stem cell transplantation
干预措施: Tumor-reduction chemotherapy and stem cell mobilization (Drug)
A2: No induction chemotherapy
Dexamethasone for control of symptoms Tumor-reduction chemotherapy and stem cell mobilization Stem cell apheresis Tandem high-dose chemotherapy Autologous peripheral blood stem cell transplantation
干预措施: Stem cell apheresis (Procedure)
A2: No induction chemotherapy
Dexamethasone for control of symptoms Tumor-reduction chemotherapy and stem cell mobilization Stem cell apheresis Tandem high-dose chemotherapy Autologous peripheral blood stem cell transplantation
干预措施: Tandem high-dose chemotherapy (melphalan) (Drug)
A2: No induction chemotherapy
Dexamethasone for control of symptoms Tumor-reduction chemotherapy and stem cell mobilization Stem cell apheresis Tandem high-dose chemotherapy Autologous peripheral blood stem cell transplantation
干预措施: Autologous peripheral blood stem cell transplantation (Procedure)
B: Observation
Tumor-reduction chemotherapy and stem cell mobilization Stem cell apheresis Tandem high-dose chemotherapy Autologous peripheral blood stem cell transplantation
干预措施: Anthracycline/dexamethasone-based induction chemotherapy (Drug)
B: Observation
Tumor-reduction chemotherapy and stem cell mobilization Stem cell apheresis Tandem high-dose chemotherapy Autologous peripheral blood stem cell transplantation
干预措施: Tumor-reduction chemotherapy and stem cell mobilization (Drug)
B: Observation
Tumor-reduction chemotherapy and stem cell mobilization Stem cell apheresis Tandem high-dose chemotherapy Autologous peripheral blood stem cell transplantation
干预措施: Stem cell apheresis (Procedure)
B: Observation
Tumor-reduction chemotherapy and stem cell mobilization Stem cell apheresis Tandem high-dose chemotherapy Autologous peripheral blood stem cell transplantation
干预措施: Tandem high-dose chemotherapy (melphalan) (Drug)
B: Observation
Tumor-reduction chemotherapy and stem cell mobilization Stem cell apheresis Tandem high-dose chemotherapy Autologous peripheral blood stem cell transplantation
干预措施: Autologous peripheral blood stem cell transplantation (Procedure)
结局指标
主要结局
Event free survival
时间窗: From randomization to 10 years follow up
Calculated according to the method of Kaplan and Meier
次要结局
- Quality of remission (Evaluation of the best response)(After last therapy to at least 6 weeks thereafter)
- Cytogenetic examination (Univariate analysis according to the method of Kaplan and Meier. Multivariate analysis according to the method of Cox´s proportional hazards regression analysis.)(From randomization to 10 years follow up)
- Overall survival(From randomization to 10 years follow up)
- Rate of remission (Evaluation of the overall response rate)(After last therapy to at least 6 weeks thereafter)
- Short and long time toxicity according to NCI Common Terminology Criteria for Adverse Events (CTCAE)(From randomization until 2 years after last therapy)