Pilot Trial of Leflunomide in Patients With High-Risk Smoldering Multiple Myeloma
概览
- 阶段
- 早期 1 期
- 干预措施
- Leflunomide
- 疾病 / 适应症
- Smoldering Plasma Cell Myeloma
- 发起方
- City of Hope Medical Center
- 入组人数
- 1
- 试验地点
- 1
- 主要终点
- Progressive disease
- 状态
- 进行中（未招募）
- 最后更新
- 3个月前
概览
简要总结
This pilot trial studies how well leflunomide works for the treatment of patients with high-risk smoldering plasma cell myeloma, for the delay of disease progression. Anti-inflammatory drugs, such as leflunomide lower the body's immune response and are used with other drugs in the treatment of some types of cancer. The information learned from this study will help researchers to learn more about the anti-myeloma activity of leflunomide, and whether it may delay the onset of symptomatic multiple myeloma in patients with high-risk smoldering multiple myeloma.
详细描述
PRIMARY OBJECTIVE: I. To estimate the anti-myeloma activity of leflunomide, when given as a single agent, as assessed by 6-month progression-free response rate based on International Myeloma Working Group (IMWG) criteria. SECONDARY OBJECTIVES: I. To evaluate the safety and tolerability of single agent leflunomide. II. To summarize and assess toxicities by type, frequency, severity, attribution, time course and duration. III. To estimate overall and progression-free survival probabilities. IV. To estimate response rate and duration of response. V. To describe the impact of treatment on quality of life, as assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Score version (v)3.0. EXPLORATORY OBJECTIVES: I. To characterize the molecular evolution of the tumor cells. II. To evaluate whether specific genetic subtypes respond differently to leflunomide. III. To evaluate the role of immune cells in the progression of smoldering multiple myeloma (SMM). IV. To evaluate the role of leflunomide in modulating the immune system. V. To examine the relationship between immunological changes and disease progression. OUTLINE: Patients receive leflunomide orally (PO) once daily (QD). Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After the completion of study treatment, patients are followed up at 30 days, every 28 days until an alternative myeloma therapy has commenced or until disease progression, and then up to 6 months.
研究者
入排标准
入选标准
- •All subjects must have the ability to understand and the willingness to sign a written informed consent
- •Patients must have a life expectancy of \> 3 months
- •Patients must exhibit an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- •Patients must have a diagnosis of high risk smoldering multiple myeloma, as defined below:
- •The presence of \>= 2 of the following risk factors:
- •Bone marrow plasma cell percentage (BMPC%) \> 20%
- •Serum M-protein \> 2 g/dL
- •Free light chain ratio (FLCr) \> 20
- •At least 2 weeks from prior therapy to time of start of treatment. Prior therapy includes steroids (except prednisone or equivalent - up to 10 mg per day is allowed)
- •Within 5 years of a diagnosis of high-risk smoldering multiple myeloma (MM)
排除标准
- •Prior treatment with leflunomide
- •Prior treatment for smoldering multiple myeloma
- •Current or planned use of other investigational agents, or concurrent biological, chemotherapy, or radiation therapy during the study treatment period. Current or planned growth factor or transfusion support until after initiation of treatment. If growth factor or transfusion support is provided between screening and start of treatment, the participant will no longer be eligible
- •Evidence of end organ damage that can be attributed to the underlying plasma cell proliferative disorder, specifically:
- •Hypercalcemia: serum calcium \> 0.25 mmol/L (\> 1 mg/dL) higher than the upper limit of normal or \> 2.75 mmol/L (\> 11 mg/dL)
- •Renal insufficiency: creatinine clearance \< 30 mL per min or serum creatinine \> 177 umol/L (\> 2 mg/dL)
- •Anemia: hemoglobin value of \> 20 g/L below the lower limit of normal, or a hemoglobin value \< 10 g/dL
- •Bone lesions: one or more osteolytic lesions on skeletal radiography, computed tomography (CT), or positron emission tomography (PET)-CT
- •Any one or more of the following biomarkers of malignancy:
- •Clonal bone marrow plasma cell percentage \>= 60%
研究组 & 干预措施
Treatment (leflunomide)
Patients receive leflunomide PO QD. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Leflunomide
Treatment (leflunomide)
Patients receive leflunomide PO QD. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Quality-of-Life Assessment
结局指标
主要结局
Progressive disease
时间窗: Up to 48 months
Will be defined by International Myeloma Working Group (IMWG) criteria. Progression to overt multiple myeloma is always considered progressive disease.
次要结局
- Incidence of toxicities(Up to 30 days after the end of treatment)
- Incidence of adverse events(Up to 30 days after end of treatment)
- Overall response rate(From the date of first documented response (confirmed complete response [CR], very good partial response [VGPR], partial response [PR] or minor response [MR]) to documented disease relapse, progression or death, assessed up to 48 months)
- Overall survival(From start date of therapy to date of death from any cause, assessed up to 48 months)
- Quality of life Questionnaire(At baseline and every 6 cycles thereafter up to 36 cycles (end of treatment), length of one complete cycle is 28 days)