2024-516908-42-00招募中2 期
A phase II multicenter study of carfilzomib, lenalidomide and dexamethasone (KRd) as induction therapy, followed by high-dose therapy with melphalan and autologous peripheral blood stem cell transplantation, consolidation with KRd, and maintenance with lenalidomide and dexamethasone in patients ≤ 70 years old with smoldering multiple myeloma (SMM) with high risk of progression to symptomatic myeloma
Fundacion PETHEMA19 个研究点 分布在 1 个国家目标入组 90 人开始时间: 2024年10月23日最近更新:
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 90
- 试验地点
- 19
- 主要终点
- • Immunophenotypic complete remission (CR by flow cytometry) day +100 after induction treatment and HDT-ASCT.
研究概览
简要总结
Evaluate the rate of patients in immunophenotypic response [i.e., complete response (CR) with minimal residual disease (MRD)-negative status using multiparametric flow cytometry (MFC) on day +100 after high-dose therapy followed by peripheral blood stem cell transplantation (HDT-ASCT or High-dose therapy / autologous stem cell transplant
研究设计
- 研究类型
- Interventional
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 是
入选标准
- •The patient must, in the investigator’s opinion, be able to fulfill all of the clinical trial requirements.
- •The patient must voluntarily sign the informed consent document before any study procedures that are not part of standard clinical care are carried out. The patient must be made aware that they can withdraw from the study at any time without this affecting their future medical care.
- •The patient must be aged between 18 and 70 years, and eligible to receive high-dose therapy and autologous peripheral blood stem cell transplant.
- •The patient must have been diagnosed with SMM with high risk of progression to symptomatic MM, or ultra-high risk of progression to symptomatic disease in the five years prior to inclusion in the study. It should be emphasized that we are referring to a diagnosis of high-risk SMM during this time period, not to monoclonal gammopathy, or intermediate or low-risk smoldering myeloma. In other words: o SMM with high risk of progression to symptomatic disease:
- •≥ 10% BM clonal PC and presence of a monoclonal protein, IgG >3 g/dl or IgA >2 g/dl or Bence Jones proteinuria of >1 g/24h and absence of lytic lesions, hypercalcemia, renal failure (creatinine < 2 mg/dl) and anemia (hemoglobin > 10 g/dl, or not 2 g/dl below the lower limit of normal.)
- •≥ 10% BM clonal PC or IgG >3 g/dl or IgA >2 g/dl, or Bence Jones proteinuria > 1 g/24 h (but not both at the same time), always in the absence of lytic lesions, hypercalcemia, renal failure and anemia. These patients can be included in the study if they fulfill the following additional criteria: - Presence of a percentage of phenotypically abnormal PC in the in plasma cell compartment of the BM (aPC/PC) ≥ 95% and immunoparesis, defined as a reduction in the concentration of 1 or 2 immunoglobulins (lgs) by more the 25%, compared with the normal values of the corresponding lg. o SMM with ultra-high risk of progression to symptomatic disease:
- •Appearance of more than 1 focal lesion on MRI (ideally whole-body MRI)
- •Clonal PC in BM ≥ 60%.
- •Ratio of involved /uninvolved sFLC greater than 100 together with involved free light chain levels great than 100 mg/L.
- •The patient must present an ECOG performance status of <
- •The patient must be able to attend scheduled visits.
- •Women with gestational capacity must have a negative pregnancy test (serum or urine) which will be taken in the 14 days prior to initiation of treatment with the study drug. Sexually active women must also agree to use two methods of contraception [hormonal contraceptives (oral, injectable, or implants)], tubal ligation, intrauterine device, barrier methods with spermicide, or her partner has had a vasectomy) while receiving the study drug. Women with gestational capacity must agree to have a pregnancy test every 4 weeks (urine or serum) while receiving the study drug (or every 14 days if they have irregular menstrual cycles), and 4 weeks after receiving the last dose of the study drug.
排除标准
- •Any physical or mental health condition that prevents the patient from signing or understanding the informed consent document.
- •The patient has experienced unstable angina or myocardial infarction in the 6 months prior to recruitment, class III or IV cardiac failure (according to the New York Heart Association criteria) uncontrolled angina, a history of acute coronary artery syndrome, uncontrolled ventricular arrhythmias, sick sinus syndrome or electrocardiographic evidence of acute ischemia or grade 3 conduction system abnormalities, unless the patient has a pacemaker.
- •Uncontrolled hypertension or diabetes.
- •Significant neuropathy (grades 3-4, or grade 2 with pain), in the 14 days prior to recruitment.
- •Known history of allergies to captisol (a derivative of cyclodextrin that is used to dissolve carfilzomib).
- •The patient presents a contraindication that prevents the administration of the concomitant or adjunctive treatments, including hydration intolerance due to pre-existing pulmonary or cardiac impairment.
- •LVEF < 40
- •Pulmonary hypertension.
- •Presence of an acute active infection that requires treatment (systemic antibiotics, antivirals, or antifungal agents), in the 14 days prior to recruitment.
- •The patient has received prior treatment for SMM.
- •The patient is pregnant or breastfeeding.
- •The patient has lytic lesions, anemia, renal failure or hypercalcemia.
- •Any of the following abnormal laboratory values: o Absolute neutrophil count (ANC) < 1,000/mm
- •o Platelet count < 75,000/mm
- •o Serum GOT or GPT > 3 times the upper limit of normal. o Total serum bilirubin > 2 times the upper limit of normal.
- •History of neoplasms other than multiple myeloma (except in the case of basal cell skin cancers, squamous cell cancers or carcinoma in situ of the cervix or breast unless the patient has been disease-free for >5 years.
- •The patient has undergone major surgery in the 4 weeks prior to inclusion in the study.
- •The patient has active HIV, hepatitis B or hepatitis C infection.
- •The patient has received an investigational drug of any type in the 4 weeks prior to inclusion in the study.
结局指标
主要结局
• Immunophenotypic complete remission (CR by flow cytometry) day +100 after induction treatment and HDT-ASCT.
• Immunophenotypic complete remission (CR by flow cytometry) day +100 after induction treatment and HDT-ASCT.
次要结局
- • Immunophenotypic complete remission (CR by flow cytometry), after consolidation and maintenance, and at 3 and 5 years post-HDT-ASCT.
- • Response rates (sCR, CR, VGPR and ORR) after the different phases of treatment (induction, HDT-ASCT, consolidation, maintenance and rescue therapy).
- • TTP to symptomatic disease, PFS and OS.
- • Safety profile after the different phases of treatment: induction, high-dose melphalan treatment and autologous hematopoietic stem cell transplantation, consolidation, maintenance and rescue therapy.
研究者
Juan José Lahuerta
Scientific
Fundacion PETHEMA
研究点 (19)
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