临床试验/NCT00689936

NCT00689936已完成3 期

A Phase III, Randomized, Open-label, 3-arm Study to Determine the Efficacy and Safety of Lenalidomide(REVLIMID) Plus Low-dose Dexamethasone When Given Until Progressive Disease or for 18 Four-week Cycles Versus the Combination of Melphalan, Prednisone, and Thalidomide Given for 12 Six-week Cycles in Patients With Previously Untreated Multiple Myeloma Who Are Either 65 Years of Age or Older or Not Candidates for Stem Cell Transplantation.

Celgene285 个研究点分布在 3 个国家目标入组 1,623 人开始时间: 2008年8月21日最近更新: 2019年11月20日

适应症

干预措施

试验速览

阶段: 3 期
状态: 已完成
发起方: Celgene
入组人数: 1,623
试验地点: 285
主要终点: Kaplan-Meier Estimates of Progression-free Survival (PFS) Based on the Response Assessment by the Independent Review Adjudication Committee (IRAC)

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

The purpose of this study is to compare the safety and efficacy of Lenalidomide plus low dose dexamethasone to that of the combination of melphalan, prednisone and thalidomide.

详细描述

CC-5013-MM020/IFM 07-01 is a Phase III, multicenter, randomized, open-label, 3-arm study that will compare the efficacy and safety of two Lenalidomide plus low-dose dexamethasone regimens given for two different durations of time (i.e., until progressive disease [PD] or for up to a maximum of 18 four-week cycles) to that of MPT given for a maximum of 12 six-week cycles.

研究设计

研究类型: Interventional
分配方式: Randomized
干预模型: Parallel
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

•Must understand and voluntarily sign informed consent form
•Age ≥ 18 years at the time of signing consent
•Previously untreated, symptomatic multiple myeloma as defined by the 3 criteria below:
•MM diagnostic criteria (all 3 required):
•Monoclonal plasma cells in the bone marrow ≥10% and/or presence of a biopsy-proven plasmacytoma
•Monoclonal protein present in the serum and/or urine
•Myeloma-related organ dysfunction (at least one of the following) [C] Calcium elevation in the blood (serum calcium >10.5 mg/dl or upper limit of normal) [R] Renal insufficiency (serum creatinine >2 mg/dl) [A] Anemia (hemoglobin <10 g/dl or 2 g < laboratory normal) [B] Lytic bone lesions or osteoporosis
•AND have measurable disease by protein electrophoresis analyses as defined by the following:
•IgG multiple myeloma: Serum monoclonal paraprotein (M-protein) level ≥ 1.0 g/dl or urine M-protein level ≥ 200 mg/24 hours
•IgA multiple myeloma: Serum M-protein level ≥ 0.5 g/dl or urine M-protein level ≥ 200 mg/24 hours
•IgM multiple myeloma (IgM M-protein plus lytic bone disease documented by skeletal survey plain films): Serum M-protein level ≥ 1.0 g/dl or urine M-protein level ≥ 200mg/24hours
•IgD multiple myeloma: Serum M-protein level ≥ 0.05 g/dl or urine M-protein level ≥ 200 mg/24 hours
•Light chain multiple myeloma: Serum M-protein level ≥ 1.0 g/dl or urine M-protein level ≥ 200 mg/24 hours
•AND are at least 65 years of age or older or, if younger than 65 years of age, are not candidates for stem cell transplantation because:
•The patient declines to undergo stem cell transplantation or
•Stem cell transplantation is not available to the patient due to cost or other reasons
•ECOG performance status of 0, 1, or 2
•Able to adhere to the study visit schedule and other protocol requirements
•Females of child-bearing potential (FCBP)^2:
•Must agree to undergo two medically supervised pregnancy tests prior to starting study therapy with either Rd or MPT. The first pregnancy test will be performed within 10-14 days prior to the start of Rd or MPT and the second pregnancy test will be performed within 24 hours prior to the start of Rd or MPT. She must also agree to ongoing pregnancy testing during the course of the study and after the end of study therapy. This applies even if the patient practices complete and continued sexual abstinence.
•Must commit to either continued abstinence from heterosexual intercourse (which must be reviewed on a monthly basis) or agree to use and be able to comply with effective contraception without interruption, 28 days prior to starting study drug, during the study therapy (including during periods of dose interruptions), and for 28 days after discontinuation of study therapy.
•Male Patients:
•Must agree to use a condom during sexual contact with a FCBP, even if they have had a vasectomy, throughout study drug therapy, during any dose interruption and after cessation of study therapy.
•Must agree to not donate semen during study drug therapy and for a period after end of study drug therapy.
•Must practice complete abstinence or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for at least 28 days following study drug discontinuation, even if he has undergone a successful vasectomy.
•All patients must:
•Have an understanding that the study drug could have a potential teratogenic risk.
•Agree to abstain from donating blood while taking study drug therapy and following discontinuation of study drug therapy.
•Agree not to share study medication with another person. All FCBP and male patients must be counseled about pregnancy precautions and risks of fetal exposure.

排除标准

•Previous treatment with anti-myeloma therapy (does not include radiotherapy, bisphosphonates, or a single short course of steroid [i.e., less than or equal to the equivalent of dexamethasone 40 mg/day for 4 days; such a short course of steroid treatment must not have been given within 14 days of randomization]).
•Any serious medical condition that places the patient at an unacceptable risk if he or she participates in this study. Examples of such a medical condition are, but are not limited to, patient with unstable cardiac disease as defined by: Cardiac events such as MI within the past 6 months, NYHA heart failure class III-IV, uncontrolled atrial fibrillation or hypertension; patients with conditions requiring chronic steroid or immunosuppressive treatment, such as rheumatoid arthritis, multiple sclerosis and lupus, that likely need additional steroid or immunosuppressive treatments in addition to the study treatment.
•Pregnant or lactating females.
•Any of the following laboratory abnormalities:
•Absolute neutrophil count (ANC) < 1,000/µL (1.0 x 109/L)
•Untransfused platelet count < 50,000 cells/µL (50 x 10^9/L)
•Serum SGOT/AST or SGPT/ALT > 3.0 x upper limit of normal (ULN)
•Renal failure requiring hemodialysis or peritoneal dialysis.
•Prior history of malignancies, other than multiple myeloma, unless the patient has been free of the disease for ≥ 3 years. Exceptions include the following:
•Basal cell carcinoma of the skin
•Squamous cell carcinoma of the skin
•Carcinoma in situ of the cervix
•Carcinoma in situ of the breast
•Incidental histological finding of prostate cancer (TNM stage of T1a or T1b)
•Patients who are unable or unwilling to undergo antithrombotic therapy.
•Peripheral neuropathy of > grade 2 severity.
•Known HIV positivity or active infectious hepatitis, type A, B, or C. Primary AL (immunoglobulin light chain) amyloidosis and myeloma complicated by amyloidosis.
•1 A variety of other types of end organ dysfunctions can occasionally occur and lead to a need for therapy. Such dysfunction is sufficient to support classification as myeloma if proven to be myeloma-related.
•2 A FCBP is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy or 2) has not been naturally postmenopausal (i.e., amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).

研究组 & 干预措施

Lenalidomide / Dexamethasone until disease progression

Experimental

Lenalidomide plus low-dose dexamethasone given until disease progression

干预措施: Lenalidomide and low-dose dexamethasone (Drug)

Lenalidomide / Dexamethasone for 18 cycles

Experimental

Lenalidomide plus low-dose dexamethasone given for 18 four-week cycles

干预措施: Lenalidomide plus low-dose dexamethasone given for 18 four-week cycles (Drug)

Melphalan, Prednisone, and Thalidomide (MPT) for 12 cycles

Active Comparator

Combination of Melphalan, Prednisone and Thalidomide given for 12 six-week cycles

干预措施: Melphalan, Prednisone and Thalidomide (Drug)

结局指标

主要结局

Kaplan-Meier Estimates of Progression-free Survival (PFS) Based on the Response Assessment by the Independent Review Adjudication Committee (IRAC)

时间窗: From date of randomization until the data cut-off date of 24 May 2013. Median follow-up time for all participants was 17.1 months.

PFS was calculated as the time from randomization to the first documented PD or death due to any cause during the study, which ever occurred first based on the International Myeloma Working Group Uniform Response criteria (IMWG). Those who withdrew for any reason or received another anti-myeloma therapy without documented PD were censored on the date of their last response assessment, prior to receiving any other anti-myeloma therapy. Censoring rules for PFS: - No baseline assessments and no progression or death documented within the 2 scheduled assessments; Death within the lst two assessments without any adequate response assessment; Progression documented between scheduled assessments; Death between adequate assessments; no progression; study discontinuations for reasons other than PD or death; new anti-myeloma started prior to PD; death or PD after an extended lost to follow-up time period (2 or more missed scheduled assessment's).

Kaplan-Meier Estimates of PFS Based on the Response Assessment by the Investigator At the Time of Final Analysis

时间窗: From date of randomization to date of data cut-off date of 21 January 2016; median follow-up for all participants was 17.7 months

次要结局

Kaplan Meier Estimates of Time to Treatment Failure (TTF)(From date of randomization until the data cut-off of 24 May 2013; median follow-up for all participants was 16.1 months.)
Kaplan Meier Estimates of Overall Survival at the Time of Final Analysis (OS)(From date of randomization to date of data cut-off date of 21 January 2016; median follow-up for all participants was 48.3 months)
Percentage of Participants With an Objective Response Based on IRAC Review(Disease response was assessed every 28 days until end of treatment or the data cut-off date of 24 May 2013; median duration of treatment was 80.2 weeks in the Rd arm; 72 weeks in the Rd18 arm and 67.1 weeks in the MPT arm)
Percentage of Participants With an Objective Response Based on Investigator Assessment at Time of Final Analysis(Disease response was assessed every 28 days until end of treatment or the data cut-off date of 21 January 2016; median duration of treatment was 80.2 weeks in the Rd arm; 72 weeks in the Rd18 arm and 67.1 weeks in the MPT arm)
Kaplan Meier Estimates of Duration of Myeloma Response as Determined by the IRAC(Disease response was assessed every 28 days until end of treatment or the data cut-off date of 24 May 2013; median follow-up for responders was 20.1 months)
Kaplan Meier Estimates of Duration of Myeloma Response as Determined by an Investigator Assessment at Time of Final Analysis(Disease response was assessed every 28 days until end of treatment; data cut-off date of 21 January 2016; median follow-up for responders was 19.9 months)
Time to First Response Based on the Review by the IRAC(Disease response was assessed every 28 days until end of treatment or the data cut-off date of 24 May 2013; median duration of treatment was 80.2 weeks in the Rd arm; 72 weeks in the Rd18 arm and 67.1 weeks in the MPT arm)
Time to First Response Based on the Investigator Assessment at the Time of Final Analysis(Disease response was assessed every 28 days until end of treatment or the data cut-off date of 21 January 2016; median duration of treatment was 80.2 weeks in the Rd arm; 72 weeks in the Rd18 arm and 67.1 weeks in the MPT arm.)
Kaplan Meier Estimates of Time to Treatment Failure (TTF) at the Time of Final Analysis(From date of randomization until the data cut-off date of 21 January 2016; median follow up for all participants was 16.1 months.)
Kaplan Meier Estimates for Time to Second-line Anti-myeloma Treatment (AMT)(From date of randomization until the data cut-off of 24 May 2013; median follow-up for all participants was 23.0 months)
Kaplan Meier Estimates of Time to Second Line Therapy AMT at the Time of Final Analysis(From date of randomization until the data cut-off of date 21 January 2016; median follow-up for all participants was 23.0 months)
Percentage of Participants With an Objective Response After Second-line Anti-myeloma Treatment at the Time of Final Analysis(Disease response was assessed every 28 days until end of treatment; data cut-off date of 21 January 2016; median duration of treatment was 80.2 weeks in the Rd arm; 72 weeks in the Rd18 arm and 67.1 weeks in the MPT arm)
Percentage of Participants With a Myeloma Response by Adverse Risk Cytogenetic Risk Category Based on IRAC Review.(Disease response was assessed every 28 days until end of treatment or the data cut-off date of 24 May 2013; median duration of treatment was 80.2 weeks in the Rd arm; 72 weeks in the Rd18 arm and 67.1 weeks in the MPT arm)
Percentage of Participants With a Myeloma Response by Favorable Hyperdiploidy Risk Cytogenetic Risk Category Based on IRAC Review(Disease response was assessed every 28 days until end of treatment or the data cut-off date of 24 May 2013; median duration of treatment was 80.2 weeks in the Rd arm; 72 weeks in the Rd18 arm and 67.1 weeks in the MPT arm)
Change From Baseline in the EORTC QLQ-C30 Cognitive Functioning Domain(Cycle 1 Day 1, (Baseline) then Months 1, 3, 6, 12, 18 and Discontinuation visit)
Percentage of Participants With a Myeloma Response by Normal Risk Cytogenetic Risk Category Based on IRAC Review(Disease response was assessed every 28 days until end of treatment or the data cut-off date of 24 May 2013; median duration of treatment was 80.2 weeks in the Rd arm; 72 weeks in the Rd18 arm and 67.1 weeks in the MPT arm)
Percentage of Participants With a Myeloma Response by Uncertain Risk Cytogenetic Risk Category Based on IRAC Review(Disease response was assessed every 28 days until end of treatment or the data cut-off date of 24 May 2013; median duration of treatment was 80.2 weeks in the Rd arm; 72 weeks in the Rd18 arm and 67.1 weeks in the MPT arm)
Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Global Health Status Domain(Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit)
Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain(Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit)
Change From Baseline in the EORTC QLQ-C30 Role Functioning Domain(Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit)
Change From Baseline in the EORTC QLQ-C30 Emotional Functioning Domain(Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit)
Change From Baseline in the EORTC QLQ-C30 Social Functioning Domain(Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit)
Change From Baseline in the EORTC QLQ-C30 Fatigue Domain(Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation)
Change From Baseline in the EORTC QLQ-C30 Pain Domain(Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit)
Change From Baseline in the EORTC QLQ-C30 Nausea/Vomiting Domain(Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit)
Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Future Perspective Scale(Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit)
Change From Baseline in the EORTC QLQ-C30 Dyspnea Domain(Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit)
Change From Baseline in the EORTC QLQ-C30 Insomnia Domain(Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit)
Healthcare Resource Utilization (HRU): Rate of Inpatient Hospitalizations Per Year(Day 1 (randomization) up to last visit completed 25 July 2016)
Change From Baseline in the EORTC QLQ-C30 Appetite Loss Domain(Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit)
Change From Baseline in the EORTC QLQ-C30 Constipation Domain(Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit)
Change From Baseline in the EORTC QLQ-C30 Diarrhea Domain(Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit)
Change From Baseline in the EORTC QLQ-C30 Financial Difficulties Domain(Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit)
Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Disease Symptoms Scale(Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit)
Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Side Effects Treatment Scale(Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit)
Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Body Image Scale(Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit)
Change From Baseline in the European Quality of Life-5 Dimensions (EQ-5D) Health Utility Index Score(Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit)
Number of Participants With Adverse Events (AEs) During the Active Treatment Phase(From first dose of study drug through 28 days following the discontinuation visit from active treatment phase; median duration of treatment was 80.2 weeks in the Rd arm; 72 weeks in the Rd18 arm and 67.1 weeks in the MPT arm)
Shift From Baseline to Most Extreme Postbaseline Value in Creatinine Clearance (CrCl) During the Active Treatment Phase(Randomization to end of treatment or the data cut off of 24 May 2013; median duration of treatment was 80.2 weeks in the Rd arm; 72 weeks in the Rd18 arm and 67.1 weeks in the MPT arm)
Shift From Baseline to Most Extreme Postbaseline Value in Absolute Neutrophil Count During the Active Treatment Phase(Randomization to end of treatment or the data cut off of 24 May 2013; median duration of treatment was 80.2 weeks in the Rd arm; 72 weeks in the Rd18 arm and 67.1 weeks in the MPT arm)
Shift From Baseline to Most Extreme Postbaseline Value in Hemoglobin During the Active Treatment Phase(Randomization to end of treatment or the data cut off of 24 May 2013; median duration of treatment was 80.2 weeks in the Rd arm; 72 weeks in the Rd18 arm and 67.1 weeks in the MPT arm)
Shift From Baseline to Most Extreme Postbaseline Value in Platelet Count During the Active Treatment Phase.(Randomization to end of treatment or the data cut off of 24 May 2013; median duration of treatment was 80.2 weeks in the Rd arm; 72 weeks in the Rd18 arm and 67.1 weeks in the MPT arm)
Improvement of Infection Rate by Observing the Historical Data Compared to the Clinical Data Base(From randomization to 24 May 2013)

研究者

发起方

Celgene

申办方类型

Industry

责任方

Sponsor

研究点 (285)

Loading locations...

相似试验

终止

3 期

Study of Lenalidomide and Dexamethasone With or Without Pembrolizumab (MK-3475) in Participants With Newly Diagnosed Treatment Naive Multiple Myeloma (MK-3475-185/KEYNOTE-185)Multiple Myeloma

NCT02579863Merck Sharp & Dohme LLC310

进行中（未招募）

3 期

GEM-CLARIDEX: Ld vs BiRdMultiple Myeloma

NCT02575144PETHEMA Foundation286

已完成

2 期

A Study of Low Dose Lenalidomide and Dexamethasone in Relapsed/Refractory Myeloma in Patients at High Risk for MyelosuppressionMultiple Myeloma

NCT00482261Peter MacCallum Cancer Centre, Australia150

进行中（未招募）

3 期

Lenalidomide and Dexamethasone With or Without Thalidomide in Treating Patients With Multiple MyelomaDS Stage I Multiple MyelomaDS Stage II Multiple MyelomaDS Stage III Multiple Myeloma

NCT00098475National Cancer Institute (NCI)452

进行中（未招募）

1 期

Study of Lenalidomide and Dexamethasone with or without Pembrolizumab in newly diagnosed and treatment-naïve Multiple Myeloma.7ewly diagnosed, treatment-naïve multiple myeloma (MM) who are ineligible for autologous stem cell transplant (auto-SCT).MedDRA version: 20.0Level: LLTClassification code 10028228Term: Multiple myelomaSystem Organ Class: 100000004864

EUCTR2015-002901-12-DEMerck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.640