Phase 2 Study Applying Innovative Minimal Residual Disease (MRD) Techniques for Participants With Previously Untreated Multiple Myeloma Treated With D-VRd Prior To and After High-dose Therapy Followed by Autologous Stem Cell Transplantation (ASCT) - TAURUS
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 200
- 试验地点
- 31
- 主要终点
- Proportion (%) of agreement and disagreement in the MRD measurements in BM (by NGS-MRD) and in the MRD measurements in peripheral blood (by MS-MRD) at post-consolidation.
研究概览
简要总结
This is a multicenter, single arm, open-label, Phase 2 study in mutiple myeloma with newly diagnosed and treatment-naïve participants for whom high-dose therapy and autologous stem cell transplantation is part of the intended treatment plan. The study is evaluating a technique called Mass Spectrometry Minimal Residual Disease (MS-MRD) using blood samples and compares it with the minimal residual disease (MRD) technique using bone marrow samples.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •18 to 70 years of age, inclusive.
- •Must have a new diagnosis of MM as per IMWG criteria.
- •Measurable disease
- •Newly diagnosed and treatment-naïve participants for whom high-dose therapy and autologous stem cell transplantation is part of the intended treatment plan.
- •Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or
- •Clinical laboratory values meeting the required criteria during screening and ≤3 days prior to receiving first study treatment dose.
- •Adequate bone marrow function.
- •Adequate liver function.
- •Adequate renal function.
- •A female of childbearing potential (FOCBP) must have two negative serum or urine pregnancy tests at screening including within 24 hours of the start of study treatment.
- •Willing to practicing at least 1 highly effective method of contraception starting 4 weeks prior to start of study treatment, while receiving study treatment including during any dose interruptions, and for at least 3 months after the last dose of any component of the study treatment.
排除标准
- •Prior or current systemic therapy or ASCT for any plasma cell dyscrasia, with the exception of emergency use of a short course (equivalent of dexamethasone 40 mg/day for a maximum 4 days) of corticosteroids before treatment.
- •History of allogenic stem cell transplantation or prior organ transplant requiring immunosuppressive therapy.
- •Peripheral neuropathy or neuropathic pain Grade 2 or higher, as defined by the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version
- •Myelodysplastic syndrome or any malignancy within 24 months of signing consent. The only exceptions are malignancies treated within the last 24 months that are considered completely cured.
- •Plasmapheresis ≤28 days of approval.
- •Radiation therapy for treatment of plasmacytoma ≤14 days of approval of enrollment.
- •Forced Expiratory Volume in 1 second (FEV1) <50% of predicted normal.
- •Concurrent medical or psychiatric condition or disease.
- •Myocardial infarction ≤6 months of enrollment, or an unstable or uncontrolled disease/condition related to or affecting cardiac function.
- •Uncontrolled cardiac arrhythmia or clinically significant electrocardiogram (ECG) abnormalities.
- •Allergy, hypersensitivity, or intolerance to boron or mannitol, corticosteroids, monoclonal antibodies or human proteins, or the excipients of daratumumab, lenalidomide, bortezomib or dexamethasone.
- •Pregnant or breast-feeding females
研究组 & 干预措施
D-VRd + ASCT + DVRD
Participants will receive daratumumab, bortezomib, lenalidomide and dexamethasone (DVRD) for 4 induction cycles prior to and 2 consolidation cycles following autologous stem cell transplantation.
Daratumumab subcutaneously (SC), 1800 mg on days 1, 8, 15 and 22 of cycle 1 and 2, on days 1 and 15 of cycle 3-6 Bortezomib SC 1.3mg/m2 on days 1, 8, 15, 22 of cycle 1-6 Lenalidomide orally 25 mg once daily on days 1-21 of cycle 1-6 Dexamethasone 20 mg once daily on days 1, 2, 8, 9, 15, 16, 22 and 23 of cycle 1-6
干预措施: Daratumumab (Drug)
D-VRd + ASCT + DVRD
Participants will receive daratumumab, bortezomib, lenalidomide and dexamethasone (DVRD) for 4 induction cycles prior to and 2 consolidation cycles following autologous stem cell transplantation.
Daratumumab subcutaneously (SC), 1800 mg on days 1, 8, 15 and 22 of cycle 1 and 2, on days 1 and 15 of cycle 3-6 Bortezomib SC 1.3mg/m2 on days 1, 8, 15, 22 of cycle 1-6 Lenalidomide orally 25 mg once daily on days 1-21 of cycle 1-6 Dexamethasone 20 mg once daily on days 1, 2, 8, 9, 15, 16, 22 and 23 of cycle 1-6
干预措施: Bortezomib (Drug)
D-VRd + ASCT + DVRD
Participants will receive daratumumab, bortezomib, lenalidomide and dexamethasone (DVRD) for 4 induction cycles prior to and 2 consolidation cycles following autologous stem cell transplantation.
Daratumumab subcutaneously (SC), 1800 mg on days 1, 8, 15 and 22 of cycle 1 and 2, on days 1 and 15 of cycle 3-6 Bortezomib SC 1.3mg/m2 on days 1, 8, 15, 22 of cycle 1-6 Lenalidomide orally 25 mg once daily on days 1-21 of cycle 1-6 Dexamethasone 20 mg once daily on days 1, 2, 8, 9, 15, 16, 22 and 23 of cycle 1-6
干预措施: Lenalidomide (Drug)
D-VRd + ASCT + DVRD
Participants will receive daratumumab, bortezomib, lenalidomide and dexamethasone (DVRD) for 4 induction cycles prior to and 2 consolidation cycles following autologous stem cell transplantation.
Daratumumab subcutaneously (SC), 1800 mg on days 1, 8, 15 and 22 of cycle 1 and 2, on days 1 and 15 of cycle 3-6 Bortezomib SC 1.3mg/m2 on days 1, 8, 15, 22 of cycle 1-6 Lenalidomide orally 25 mg once daily on days 1-21 of cycle 1-6 Dexamethasone 20 mg once daily on days 1, 2, 8, 9, 15, 16, 22 and 23 of cycle 1-6
干预措施: Dexamethasone (Drug)
结局指标
主要结局
Proportion (%) of agreement and disagreement in the MRD measurements in BM (by NGS-MRD) and in the MRD measurements in peripheral blood (by MS-MRD) at post-consolidation.
时间窗: Up to 12 months
The proportion (%) of agreement will be defined as the total number of concordant cases (i.e., MRD-positive by both techniques, MRD-negative by both techniques) versus the total number of cases with available results.
次要结局
- Proportion (%) of agreement and disagreement in the MRD measurements in BM (by NGF-MRD) and in the MRD measurements in peripheral blood (by MS-MRD) at post-induction and post-consolidation.(Up to 12 months)
- ORR, VGPR or better, CR or better, sCR at post-induction, post-transplant, post-consolidation and overall.(Up to 12 months)
- MRD negativity rate BM-MRD and PB-MRD(Up to 12 months)
- Effect of cytogenetic abnormalities (presence or not), R-ISS (1, 2 or 3), CTCs (number of cells per ml) on likelihood to develop MRD-negative disease (with MS, NGS and NGF) and the agreement between the different techniques.(Up to 12 months)
- Proportion (%) of agreement and disagreement in the MRD measurements in BM (by NGS-MRD) and in the MRD measurements in peripheral blood (by MS-MRD) at post-induction.(Up to 4 months and 2 weeks)
- Proportion (%) of agreement and disagreement in the MRD measurements in BM by NGF-MRD and NGS-MRD at post-induction and post-consolidation.(Up to 12 months)