A MULTICENTER, RANDOMIZED, OPEN LABEL PHASE II STUDY OF CARFILZOMIB, CYCLOPHOSPHAMIDE AND DEXAMETHASONE (CCyd) as Pre Transplant INDUCTION and Post Transplant Consolidation or CARFILZOMIB, LENALIDOMIDE AND DEXAMETHASONE (CRd) as Pre Transplant INDUCTION and Post Transplant Consolidation or Continuous Treatment With CARFILZOMIB, LENALIDOMIDE AND DEXAMETHASONE (12 Cycles) Without Transplant, All Followed by MAINTENANCE With LENALIDOMIDE (R) Versus LENALIDOMIDE AND CARFILZOMIB (CR) IN NEWLY DIAGNOSED MULTIPLE MYELOMA (MM) PATIENTS ELEGIBLE FOR AUTOLOGOUS TRANSPLANT
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 477
- 试验地点
- 2
- 主要终点
- Efficacy in term of at least Very Good Partial Response (VGPR)
研究概览
简要总结
This study will evaluate the safety and the efficacy of carfilzomib combined with cyclophosphamide and dexamethasone (CCyd) or lenalidomide and dexamethasone (CRd) followed by autologous transplantation ASCT or 12 cycles of carfilzomib combined with dexamethasone and lenalidomide for patients eligible for ASCT with newly diagnosed multiple myeloma. As a secondary endpoint this study will evaluate the best maintenance treatment between lenalidomide and lenalidomide combined with carfilzomib.
Four hundred seventy-seven patients, males and females aged > 18 years, enrolled in several sites, will take part in this study.
The duration of the study is approximately 5 years.
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
- •Age ≥ 18 years Newly diagnosed MM based on standard CRAB criteria (see appendix B). Patient < 65 years eligible for ASCT. Patient has measurable disease according to IMWG (International Myeloma Working Group) criteria.
- •Patient has given voluntary written informed consent. Patient agrees to use acceptable methods for contraception. Patient has a Karnofsky performance status ≥ 60%
- •Pretreatment clinical laboratory values within 30 days of enrolment:
- •Platelet count ≥50 x 109/L (≥30 x 109 /L if myeloma involvement in the bone marrow is > 50%) Absolute neutrophil count (ANC) ≥ 1 x 109/L without the use of growth factors Corrected serum calcium ≤14 mg/dL (3.5 mmol/L) Alanine transaminase (ALT): ≤ 3 x the Upper Limit Normal (ULN) Total bilirubin: ≤ 2 x the ULN Calculated or measured creatinine clearance: ≥ 30 mL/minute. LVEF≥40%. 2-D transthoracic echocardiogram (ECHO) is the preferred method of evaluation. Multigated Acquisition Scan (MUGA) is acceptable if ECHO is not available Life expectancy ≥ 3 months
排除标准
- •Previous treatment with anti-myeloma therapy (does not include radiotherapy, bisphosphonates, or a single short course of steroid < to the equivalent of dexamethasone 40 mg/day for 4 days) Patients with non-secretory MM unless serum free-light chains are present and the ratio is abnormal or a plasmocytoma with minimum largest diameters of > 2 cm Patients ineligible for autologous transplantation Pregnant or lactating females
- •Presence of:
- •Clinical active infectious hepatitis type A, B, C or HIV Acute active infection requiring antibiotics or infiltrative pulmonary disease Myocardial infarction or unstable angina ≤ 4 months or other clinically significant heart disease Peripheral neuropathy or neuropathic pain grade 2 or higher, as defined by National Cancer Institute Common Toxicity Criteria (NCI CTC) 4.0 Known history of allergy to Captisol ® (a cyclodextrin derivative used to solubilize carfilzomib) Contraindication to any of the required drugs or supportive treatments Invasive malignancy within the past 3 years Serious medical condition, laboratory abnormality or psychiatric illness that prevented the subject from the enrolment or place the subject at unacceptable risk.
研究组 & 干预措施
CCyd
Carfilzomib Cyclophosphamide and Dexamethasone administered for 4 28-day cycles. This treatment will be followed by autologous stem cell transplantation (ASCT). Carfilzomib Cyclophosphamide and Dexamethasone administered for 4 28-day cycles, as consolidation treatment.
After the end of consolidation all patients will be randomized to receive:
Lenalidomide or Lenalidomide and Carfilzomib until any sign of progression or intolerance.
干预措施: Cyclophosphamide (Drug)
CCyd
Carfilzomib Cyclophosphamide and Dexamethasone administered for 4 28-day cycles. This treatment will be followed by autologous stem cell transplantation (ASCT). Carfilzomib Cyclophosphamide and Dexamethasone administered for 4 28-day cycles, as consolidation treatment.
After the end of consolidation all patients will be randomized to receive:
Lenalidomide or Lenalidomide and Carfilzomib until any sign of progression or intolerance.
干预措施: Carfilzomib (Drug)
CRd long treatment
Carfilzomib Lenalidomide and Dexamethasone administered for 4 28-day cycles. Stem cells collection will be performed. Carfilzomib Lenalidomide and Dexamethasone administered for 8 28-day cycles.
After that all patients will be randomized to receive:
Lenalidomide or Lenalidomide and Carfilzomib until any sign of progression or intolerance.
干预措施: Carfilzomib (Drug)
CRd
Carfilzomib Lenalidomide and Dexamethasone administered for 4 28-day cycles. This treatment will be followed by autologous stem cell transplantation (ASCT). Carfilzomib Cyclophosphamide and Dexamethasone administered for 4 28-day cycles, as consolidation treatment.
After the end of consolidation all patients will be randomized to receive:
Lenalidomide or Lenalidomide and Carfilzomib until any sign of progression or intolerance.
干预措施: Lenalidomide (Drug)
CCyd
Carfilzomib Cyclophosphamide and Dexamethasone administered for 4 28-day cycles. This treatment will be followed by autologous stem cell transplantation (ASCT). Carfilzomib Cyclophosphamide and Dexamethasone administered for 4 28-day cycles, as consolidation treatment.
After the end of consolidation all patients will be randomized to receive:
Lenalidomide or Lenalidomide and Carfilzomib until any sign of progression or intolerance.
干预措施: Dexamethasone (Drug)
CRd
Carfilzomib Lenalidomide and Dexamethasone administered for 4 28-day cycles. This treatment will be followed by autologous stem cell transplantation (ASCT). Carfilzomib Cyclophosphamide and Dexamethasone administered for 4 28-day cycles, as consolidation treatment.
After the end of consolidation all patients will be randomized to receive:
Lenalidomide or Lenalidomide and Carfilzomib until any sign of progression or intolerance.
干预措施: Carfilzomib (Drug)
CRd long treatment
Carfilzomib Lenalidomide and Dexamethasone administered for 4 28-day cycles. Stem cells collection will be performed. Carfilzomib Lenalidomide and Dexamethasone administered for 8 28-day cycles.
After that all patients will be randomized to receive:
Lenalidomide or Lenalidomide and Carfilzomib until any sign of progression or intolerance.
干预措施: Lenalidomide (Drug)
CRd
Carfilzomib Lenalidomide and Dexamethasone administered for 4 28-day cycles. This treatment will be followed by autologous stem cell transplantation (ASCT). Carfilzomib Cyclophosphamide and Dexamethasone administered for 4 28-day cycles, as consolidation treatment.
After the end of consolidation all patients will be randomized to receive:
Lenalidomide or Lenalidomide and Carfilzomib until any sign of progression or intolerance.
干预措施: Dexamethasone (Drug)
CRd long treatment
Carfilzomib Lenalidomide and Dexamethasone administered for 4 28-day cycles. Stem cells collection will be performed. Carfilzomib Lenalidomide and Dexamethasone administered for 8 28-day cycles.
After that all patients will be randomized to receive:
Lenalidomide or Lenalidomide and Carfilzomib until any sign of progression or intolerance.
干预措施: Dexamethasone (Drug)
结局指标
主要结局
Efficacy in term of at least Very Good Partial Response (VGPR)
时间窗: Up to 2 years
The efficacy, in term of at least VGPR, of the combination of carfilzomib, dexamethasone with cyclophosphamide or lenalidomide after 4 cycles of induction treatment in newly diagnosed MM patients eligible for ASCT.
次要结局
- sCR rate(up to 1 year)
- Safety as incidence of grade 3/4 adverse events(Up to 3 years)
- Survival(Up to 5 years)
- Correlation between tumor response and outcome with baseline prognostic factors.(up to 5 years)
- Minimal Residual Disease (MRD)(up to 5 years)
- Survival after relapse(up to 7 years)
研究者
Mario Boccadoro
MD
University of Turin, Italy