A Randomized Phase III Non-inferiority Trial Assessing Lenalidomide, Bortezomib and Dexamethasone Induction Therapy With Either Intravenous or Subcutaneous Isatuximab in Transplant-eligible Patients With Newly Diagnosed Multiple Myeloma.
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 514
- 试验地点
- 91
- 主要终点
- Demonstration of non-inferiority of subcutaneous (SC) isatuximab compared to intravenous (IV) isatuximab, both in combination with RVd.
研究概览
简要总结
The trial aims to demonstrate the non-inferiority of subcutaneous to intravenous isatuximab administration in transplant-eligible patients with newly diagnosed multiple myeloma.
详细描述
Prospective, multicentre, randomised, parallel group, open, phase III clinical trial, for patients with confirmed diagnosis of untreated multiple myeloma requiring systemic therapy.
Investigational Medicinal Product: Isatuximab, subcutaneous administration via a wearable injector system.
Randomization: Patients are randomized in one of 2 study arms (A or B) before induction therapy. Patients randomized in arm A will receive 3 cycles of the monoclonal antibody isatuximab intravenously, combined with RVd regimen (Lenalidomide, Bortezomib, Dexamethasone). Each cycle will last for 42 days. Patients in arm B will receive 3 cycles RVd plus isatuximab subcutaneously. After induction therapy, patients will receive standard intensification (usually cyclophosphamide-based mobilization therapy, stem cell collection and high-dose melphalan followed by autologous stem cell transplantation (HDM/ASCT)). End of study will be after the first HDM/ASCT.
There is one primary objective:
Demonstration of non-inferiority of subcutaneous (SC) isatuximab compared to intravenous (IV) isatuximab, both in combination with RVd, with respect to rates of VGPR or better after induction therapy (according to standard International Myeloma Working Group (IMWG) response criteria).
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Confirmed diagnosis of untreated MM requiring systemic therapy (diagnostic criteria according to IMWG)
- •Patient is eligible for high-dose melphalan (200 mg/m^2 melphalan) and autologous stem cell transplantation
- •Measurable MM disease according to IMWG criteria, defined as any quantifiable monoclonal protein value, defined by at least one of the following three measurements: serum M-protein ≥ 10 g/L; urine light-chain (M-protein) of ≥ 200 mg/24 hours; involved FLC level ≥ 10 mg/dL provided sFLC ratio is abnormal
- •Age 18-70 years at trial inclusion
排除标准
- •Patient has known hypersensitivity (or contraindication) to any of the components of study therapy
- •Systemic amyloid light-chain amyloidosis (except for localized AL amyloidosis limited to the skin or the bone marrow)
- •Plasma cell leukemia
- •Previous chemotherapy or radiotherapy during the past 5 years except local radiotherapy in case of local MM progression
- •Severe cardiac dysfunction (NYHA classification III-IV)
- •Patients with active or uncontrolled hepatitis B or C or detectable liver disease due to hepatitis B or C
- •HIV positivity
- •Patients with active, uncontrolled infections
- •Patients with severe renal insufficiency or requiring hemodialysis
- •Patients with peripheral neuropathy or neuropathic pain, grade 2 or higher (as defined by the NCI Common Terminology Criteria for Adverse Events)
- •Patients with a history of any active malignancy during the past 5 years with the exception of following malignancies after curative therapy: basal cell carcinoma of the skin, squamous cell skin carcinoma, stage 0 cervical carcinoma or any in situ malignancy
- •Platelet count < 75 x 10^9/L
- •Haemoglobin ≤ 8.0 g/dL, unless related to MM
- •Absolute neutrophil count (ANC) < 1.0 x 10^9/L (the use of colony stimulating factors within 14 days before the test is not allowed)
- •Corrected serum calcium > 14 mg/dL (> 3.5 mmol/L)
- •Pregnancy and lactation
- •For further details on inclusion/exclusion criteria please refer to the study protocol.
研究组 & 干预措施
Arm A - Intravenous isatuximab
Patients in arm A are treated with 3 cycles RVd + i.v. isatuximab, followed by a standard intensification and autologous stem cell transplantation.
干预措施: Bortezomib (Drug)
Arm A - Intravenous isatuximab
Patients in arm A are treated with 3 cycles RVd + i.v. isatuximab, followed by a standard intensification and autologous stem cell transplantation.
干预措施: Isatuximab (Drug)
Arm A - Intravenous isatuximab
Patients in arm A are treated with 3 cycles RVd + i.v. isatuximab, followed by a standard intensification and autologous stem cell transplantation.
干预措施: Lenalidomide (Drug)
Arm A - Intravenous isatuximab
Patients in arm A are treated with 3 cycles RVd + i.v. isatuximab, followed by a standard intensification and autologous stem cell transplantation.
干预措施: Dexamethasone (Drug)
Arm B - Subcutaneous isatuximab
Patients in arm B are treated with 3 cycles RVd + s.c. isatuximab, followed by a standard intensification and autologous stem cell transplantation.
干预措施: Isatuximab (Drug)
Arm B - Subcutaneous isatuximab
Patients in arm B are treated with 3 cycles RVd + s.c. isatuximab, followed by a standard intensification and autologous stem cell transplantation.
干预措施: Lenalidomide (Drug)
Arm B - Subcutaneous isatuximab
Patients in arm B are treated with 3 cycles RVd + s.c. isatuximab, followed by a standard intensification and autologous stem cell transplantation.
干预措施: Bortezomib (Drug)
Arm B - Subcutaneous isatuximab
Patients in arm B are treated with 3 cycles RVd + s.c. isatuximab, followed by a standard intensification and autologous stem cell transplantation.
干预措施: Dexamethasone (Drug)
结局指标
主要结局
Demonstration of non-inferiority of subcutaneous (SC) isatuximab compared to intravenous (IV) isatuximab, both in combination with RVd.
时间窗: 18 weeks after start of study treatment
Rates of VGPR or better (according to standard IMWG response criteria), defined as proportion of patients with at least VGPR after induction therapy (according to standard International Myeloma Working Group (IMWG) response criteria).
次要结局
- Quality of life compared between Arm A and B.(18 weeks after start of study treatment)
- Rates of best overall response to treatment (BOR)(Depending on the timepoint of best response out of all response assessments, up to 10 months from randomization)
- Progression-free survival (PFS)(Until EOS (28 months after start of study))
- Non-inferiority of rates of MRD negativity in Arm B compared to Arm A(18 weeks after start of study treatment)
- Rates of MRD negativity by NGS and NGF (sensitivity 10^-5, from BMA) independent of standard IMWG response after first HDM/ASCT(18 weeks (timepoint "after induction") or 35 weeks (timepoint "after first HDM/ASCT") after start of study treatment)
研究者
Prof. Dr. Hartmut Goldschmidt
Principal Investigator
University of Heidelberg Medical Center