An Open Label, Multicenter, Phase II Study of Elranatamab as Single Agent for the Treatment of Relapsed or Refractory Myeloma in Patients Previously Exposed to Three-drug Classes (GEM-RANTAB)
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 50
- 试验地点
- 28
- 主要终点
- To evaluate the rate of Undetectable Measurable Residual Disease (uMRD) at 6 and 12 months as per International Myeloma Working Group (IMWG) criteria evaluated by the investigators of elranatamab in patients with relapsed/refractory multiple myeloma.
研究概览
简要总结
The goal of this phase II, open-label, single-arm, multicenter study is to evaluate i) the efficacy and ii) safety of elranatamab monotherapy at the dose of 76 mg subcutaneously in participants with RRMM after at least one or two prior lines of therapy who have received prior treatment with immunomodulatory drugs, protease inhibitors, and anti-CD38 therapy and were refractory to the last line of therapy, defined as progression while receiving treatment or in the first 60 days after the last dose of treatment.
Efficacy refers to the rate of Undetectable Measurable Residual Disease at 6 and 12 months as per International Myeloma Working Group (IMWG) criteria evaluated by the investigators.
Safety refers to the measurement of:
i) Adverse events (AEs) and serious adverse events (SAEs) according to standard clinical and laboratory tests (hematology and chemistry, physical examination, vital sign measurements, and diagnostic tests).
ii) Incidence and severity of Cytokine Release Syndrome (CRS) and Immune effector cell associated neurotoxicity syndrome (ICANS) according to the American Society for Transplantation and Cellular Therapy (ASTCT) criteria.
iii) Incidence and severity of other neurotoxicities. iv) Incidence of cytopenias and infections
The study consists of a screening/baseline period, a treatment period, and a posttreatment follow-up period. The study includes a periodic review of safety data, that will be independently analyzed by the Data Safety Independent Committee (DSMC) and will recommend how to proceed with the study.
详细描述
Treatment with elranatamab will be initiated using a 2-step-up priming regimen: the initial doses of elranatamab will be 12 mg (Cycle 1 Day 1) and 32 mg (Cycle1 Day 4). Participants should be hospitalized and monitored for toxicity (especially CRS/ICANS) for at least 2 days (~48 hours) beginning on Cycle 1 Day 1, and for 1 day (~24 hours) for Cycle1 Day 4. The dose of elranatamab should be increased to 76 mg on Cycle 1 Day 8 as long as the participant meets the redosing criteria or deferred until the criteria are met.
The scheme of administration includes weekly administrations for at least six 4-weeks cycles and, if patients have achieved at least PR (or better) persisting for at least 2 months, the dose interval should be changed from weekly to every other week. Treatment will be scheduled with a response-adapted duration and patients achieving undetectable measurable residual disease and maintained for 12 months will stop therapy. After stopping therapy, and if the patient is in sustained undetectable measurable residual disease for at least 12 months, it would be possible to re-start treatment with elranatamab in case the measurable residual disease will be detectable or relapse from CR will occur. Patients who will not achieve undetectable measurable residual disease sustained for 12 months will receive continuous treatment until progressive disease. In both situations, the occurrence of unacceptable toxicity might result into the treatment discontinuation.
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
盲法说明
None (Open Label)
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
- •Male or female, 18 years or older (at the time consent is obtained).
- •Patient who, in the investigator's opinion, is able to comply with the protocol requirements.
- •Prior diagnosis of MM as defined according to IMWG criteria.
- •Patient has given voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care.
- •Relapse multiple myeloma patients that have received at least 1 or 2 prior lines of therapy including at least to one proteasome inhibitor (bortezomib, carfilzomib or ixazomib), one immunomodulatory drug (lenalidomide is mandatory and patients can be also have been exposed to pomalidomide) and at least one anti-CD38 monoclonal antibody (daratumumab or isatuximab).
- •Patients must be refractory to the last line of therapy, defined as progression while receiving treatment or in the first 60 days after the last dose of treatment.
- •Patient must have a measurable secretory disease defined as either serum monoclonal protein of ≥ 0,5 g/dl or urine monoclonal (light chain) protein ≥ 200 mg/24 h. For patients in whom disease is only measurable by serum FLC, the involved FLC should be ≥ 10mg/dL (100 mg/L), with an abnormal serum FLC ratio.
排除标准
- •Subject has a diagnosis of primary amyloidosis, monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), POEMS syndrome (defined by the presence of peripheral neuropathy, organomegaly, endocrinopathy, monoclonal plasma-cells proliferative disorder, and skin changes) or plasma cell leukemia.
- •Prior anti-BCMA treatment.
- •Subject has peripheral neuropathy or neuropathic pain grade 2 or higher, as defined by the National Cancer Institute Terminology Criteria for Adverse Events (NCI CTCAE) Version
- •History of Guillain-Barré syndrome (GBS) or GBS variants, or history of any Grade ≥3 peripheral motor polyneuropathy.
- •Stem cell transplant within 12 weeks prior to enrolment.
研究组 & 干预措施
Elranatamab
Elranatamab will be administered by subcutaneous (SC) injection
干预措施: Elranatamab (PF-06863135) (Drug)
结局指标
主要结局
To evaluate the rate of Undetectable Measurable Residual Disease (uMRD) at 6 and 12 months as per International Myeloma Working Group (IMWG) criteria evaluated by the investigators of elranatamab in patients with relapsed/refractory multiple myeloma.
时间窗: 5 Years
To evaluate the rate of uMRD at 6 and 12 months (defined as the percentage of participants who are MRD negative by next generation flow cytometry (NGF) method and with a sensitivity level of at least 10-5) of elranatamab in patients with relapsed/refractory multiple myeloma. Next generation flow cytometry is a reproducible biomarker to detect the presence of phenotypically abnormal clonal plasma cells (Measurable Residual Disease). The presence of surface markers (CD138, CD27, CD38, CD56, CD45, CD19) and certain morphological characteristics (FSC and SSC) permit the specific identification of plasma cells (PC). This will permit unique, high specificity confirmation of the monoclonality of phenotypically abnormal plasma cells (by light chain restriction). Said cells will have been clearly identified by low antigen expression (CD19, CD27, CD38, CD45, CD81) or overexpression (CD56, CD117, CD138).
次要结局
- To determine serum BCMA levels and its correlation with response.(5 Years)
- To do gene expression techniques (RNA sequencing and single cell sequencing studies) coupled with intelligent clinical and molecular data analysis (i.e. machine learning) to identify factors that could predict response to elranatamab.(5 Years)
- To evaluate annually by NGF until loss of response, the rate of Undetectable Measurable Residual Disease (% of patients with MRD negative by NGF method and with a sensitivity level of 10-5) of elranatamab in patients with R/R multiple myeloma.(5 Years)
- Incidence and severity Adverse Events (AEs) and Serious Adverse Event (SAEs) as assessed by changes in laboratory values in blood and biochemistry tests.(5 Years)
- Incidence and severity Adverse Events (AEs) and Serious Adverse Event (SAEs) as assessed by changes in physical examination and ECOG performance status scale (0-5).(5 Years)
- Incidence and severity Adverse Events (AEs) and Serious Adverse Event (SAEs) as assessed by changes in vital sign measurements.(5 Years)
- Incidence and severity Adverse Events (AEs) and Serious Adverse Event (SAEs) as assessed by pregnancy test.(5 Years)
- Incidence and severity Adverse Events (AEs) and Serious Adverse Event (SAEs) as assessed by changes in 12-lead ECG.(5 Years)
- Incidence and severity Adverse Events (AEs) and Serious Adverse Event (SAEs) as assessed by changes in Echocardiogram / MUGA.(5 Years)
- To determine Circulating Tumor Cells (CTC) at baseline to evaluate its prognostic value.(5 Years)
- To determine MRD value with alternative methods(5 Years)
- To characterize patients' immune system(5 Years)
- To evaluate Overall Response Rate of elranatamab in patients with relapsed/refractory multiple myeloma.(5 years)
- To evaluate Time to first and best response of elranatamab in patients with relapsed/refractory multiple myeloma.(5 years)
- To define genomic determinants of response/resistance(5 Years)
- To evaluate Duration of Response of elranatamab in patients with relapsed/refractory multiple myeloma.(5 years)
- To evaluate Progression-free survival (PFS) of elranatamab in patients with relapsed/refractory multiple myeloma.(5 years)
- To evaluate Overall survival (OS) of elranatamab in patients with relapsed/refractory multiple myeloma.(5 years)
- To evaluate PFS in those patients who stop treatment because of sustained MRD-positive for 12 months of elranatamab in patients with relapsed/refractory multiple myeloma.(5 yerars)
- To evaluate OS in those patients who stop treatment because of sustained MRD-positive for 12 months of elranatamab in patients with relapsed/refractory multiple myeloma.(5 yerars)
- To evaluate the Incidence of neurologic effects related to elranatamab in patients with relapsed/refractory multiple myeloma.(5 years)
- To evaluate the Incidence of cytopenias and infections related to elranatamab in patients with relapsed/refractory multiple myeloma.(5 years)