Lenalidomide and Low Dose Dexamethasone Induction Therapy Followed by Low Dose Melphalan, Prednisone, Lenalidomide and Bortezomib Sequential Maintenance Therapy for Newly Diagnosed High-risk Multiple Myeloma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Progression Free Survival
研究概览
简要总结
The purpose of this study is to evaluate the effectiveness of induction therapy with lenalidomide and low dose dexamethasone followed by sequential low dose bortezomib followed by low dose Melphalan and Prednisone, then followed by low dose lenalidomide for multiple cycles in subjects with high risk Multiple Myeloma (MM). The primary objective is to evaluate the efficacy as measured by the progression free survival (PFS) at 2 years of low dose sequential therapy following four cycles of induction therapy with lenalidomide/low-dose dexamethasone in subjects with symptomatic high risk multiple myeloma, who have received no prior treatment. A total of 35 subjects were estimated to be accrued to this Phase II trial over a period of subjects who are still progression-free at 2 years. Two years will be as measured from date of registration to the trial. Progression will include disease progression (DP) as well as death due to any cause. Data will be analyzed and reported by the PI after 1 and 2 years of initiation of the study. All subsequent data collected may be analyzed and reported in a follow-up clinical report. The PI and independent reviewers will meet to review the efficacy and safety data and determine a risk/benefit analysis in this subject population.
详细描述
Study design: A total of 35 subjects who were newly diagnosed, high risk Multiple Myeloma (high risk defined by the presence of one or more of the following: t(4;14), t(14;16), deletion of 17p13 (p53) by FISH, deletion of chromosome 13 or aneuploidy on metaphase analysis) were estimated to be accrued to this Phase II trial over a period of about 3 years.
The primary objective is to estimate the proportion of subjects who are still progression-free at 2 years. Two years is measured from date of registration to the trial. Progression will include disease progression as well as death due to any cause. Time to response, defined only for the responders, is defined as the time from the date of initiation of treatment to the first documentation of a confirmed response. Duration of response among subjects achieving a sustained complete response (sCR), complete response (CR), very good partial response (VGPR) or partial response (PR) will be defined as the length of the interval from initial PR to time of disease progression. Progression free survival (PFS) is defined for all subjects as the time from the date of initiation of treatment to the date of first documentation of relapse, progression, or death due to any cause. Time to progression (TTP) is defined for all subjects as the time from initiation of treatment to disease progression with deaths owing to causes other than progression not counted as events, but censored (Durie et al., 2006). Overall survival (OS) is defined as the time from the date of initiation of treatment to the date of death due to any cause. The Garban et al. trial found a 2-year progression-free rate of about 0.60 in 212 similar subjects. If a 2-year rate of 0.60 were to be observed in this trial, we would consider the treatment a success. A rate of 0.60 has an exact 80% confidence interval (CI) of 0.48 - 0.71.
True 2-year Probability of observing Progression-free a rate ≥ 0.60 0.48 0.11 0.52 0.22 0.56 0.38 0.60 0.57 0.64 0.75 0.68 0.88 0.72 0.95
DOSING REGIMEN(S):
Induction therapy: Lenalidomide 25 mg daily on Days 1-21 followed by 7 day rest and Dexamethasone 40 mg by mouth (po) daily on Days 1, 8, 15 and 22 every 28 days for 4 cycles. Subjects will receive 325 mg aspirin for deep vein thrombosis (DVT) prophylaxis.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Understand and voluntarily sign an informed consent form.
- •Age 18 years or older at the time of signing the consent.
- •Able to adhere to the study visit schedule and other protocol requirements.
- •Multiple myeloma (MM) diagnosed according to the following standard criteria:
- •Monoclonal plasma cells in bone marrow ≥10% and/or presence of biopsy-proven plasmacytoma
- •Monoclonal protein present in serum and/or urine Myeloma-related organ dysfunction (1 or more) (C) Calcium elevation in blood (serum calcium >10.5 mg/L or ULN) (R) Renal insufficiency (SCr >2 mg/dL) (A) Anemia (hemoglobin <10 g/dL or 2g <normal) (B) Lytic bone lesions or osteoporosis
- •Measurable disease requiring systemic therapy.
- •High risk multiple myeloma defined by the presence of one or more of the following:
- •Deletion of chromosome 13 by metaphase analysis (standard cytogenetics)
- •deletion of 17p13 (p53) by Fluorescence in situ hybridization (FISH) or metaphase analysis
- •t(4;14) by FISH
- •t(14;16) by FISH
- •t(8;14) by FISH
- •t(14;20) by FISH
- •hypodiploidy detected by FISH or metaphase analysis
- •any complex cytogenetic abnormality detected by metaphase analysis, with the exception of hyperdiploidy
- •No previous treatment with systemic therapy or radiation therapy lasting more than 4 weeks duration.
- •At least 7 days since date of last radiation or systemic treatment for MM.
- •Eastern Cooperative Oncology Group (ECOG) performance status of < or =2 at study entry.(0=Fully active; 1=Restricted but ambulatory; 2=Ambulatory but unable to work)
- •All study participants must be registered into the mandatory RevAssist® program, and willing and able to comply with the requirements.
- •Females of childbearing potential (FCBP) must have negative pregnancy test with a sensitivity of >/=50 milli-International unit (mIU)/mL within 10-14 days prior to and within 24 hours of prescribing lenalidomide and must use 2 acceptable methods of birth control, one highly effective method and one other effective method AT THE SAME TIME, >4 weeks before taking lenalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree not to father a child and agree to use a latex condom even if he has had a successful vasectomy, if partner is FCBP.
- •Disease free of prior malignancies for >5 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "insitu" of the cervix or breast
- •Able to take 325 mg aspirin daily as prophylactic anticoagulation for the duration of protocol therapy.
- •Receive concomitant therapy with bisphosphonates if bony lesions are present at time of enrollment.
- •Exclusion criteria
- •Any serious medical condition, laboratory abnormality, or psychiatric illness to prevent the subject from signing the consent.
- •Pregnant or breast feeding females.
- •Any condition which places the subject at unacceptable risk or confounds the ability to interpret data from the study.
- •Abnormal laboratory test results within these ranges:
- •Absolute neutrophil count < 1.0 x 109/L
- •Platelet count < 50 x 109/L (Subjects with severe pancytopenia (not meeting the above criteria) due to myeloma involvement of > 70% bone marrow are eligible)
- •Serum creatinine > 2.5 mg/dL or ≥ 3.0 mg/dL if due to multiple myeloma.
- •Total bilirubin > 2.0 mg/dl
- •History of allergy to any of the study medications, their analogues, or excipients in the various formulations
- •Concurrent use of other anti-cancer agents or treatments.
- •Known HIV positivity
- •Known Active Hepatitis A, B or C
- •Erythema nodosum characterized by a desquamating rash while taking thalidomide or similar drug.
排除标准
- 未提供
研究组 & 干预措施
High-risk Multiple Myeloma
Lenalidomide Induction (with Low Dose Dexamethasone) Therapy Followed by Low Dose Melphalan, Prednisone, Lenalidomide and Bortezomib Sequential Maintenance Therapy
干预措施: Lenalidomide Induction (Drug)
High-risk Multiple Myeloma
Lenalidomide Induction (with Low Dose Dexamethasone) Therapy Followed by Low Dose Melphalan, Prednisone, Lenalidomide and Bortezomib Sequential Maintenance Therapy
干预措施: Sequential Maintenance Therapy (Drug)
结局指标
主要结局
Progression Free Survival
时间窗: 2 years
Progression free survival (PFS) is defined for all subjects as the time from the date of initiation of treatment to the date of first documentation of relapse, progression, or death due to any cause. Full restaging was performed at 6, 12, 18, 24, 36, 48, 60, 72 months). PFS survival will be estimated and plotted with the Kaplan-Meier method. The median will be calculated with 95% confidence intervals.
次要结局
- Time to Response(6 months)
- Overall Survival(6 years)
- Time to Progression(6 years)
- Duration of Response(6 years)
研究者
Cristina Gasparetto
Associate Professor of Medicine
Duke University