Study of Treatment for Newly Diagnosed Multiple Myeloma Patients Older Than 65 Years With Sequential Melphalan/Prednisone/Velcade (MPV) Followed by Revlimid/Low Dose Dexamethasone (Rd) Versus Alternating Velcade/Melphalan/Prednisone (MPV) With Revlimid/Low Dose Dexamethasone
A National, Open-label, Multicenter, Randomized, Comparative Phase IIb Study of Treatment for Newly Diagnosed Multiple Myeloma Patients Older Than 65 Years With Sequential Melphalan/Prednisone/Velcade (MPV) Followed by Revlimid/Low Dose Dexamethasone (Rd) Versus Alternating Velcade/Melphalan/Prednisone (MPV) With Revlimid/Low Dose Dexamethasone (Rd).
This is a national, multicenter, open-label, randomized, comparative study designed to compare, first, the TTP of the two treatment schemes proposed (MPV followed by Rd or MPV alternating with Rd) in newly diagnosed MM patients older than 65 years. This comparison will be performing in terms of both efficacy and safety. Up to 120 patients will be included in each treatment arm and evaluated at scheduled visits in up to 3 study periods: Pre-treatment, Treatment and Follow-up.
Primary outcome measure:
- To evaluate the efficacy in terms of time to progression (TTP) at 18 months of MPV and Rd used as either in a sequential or alternating approach in newly diagnosed MM patients older than 65 years.
- To evaluate the toxicity (safety and tolerability) of the sequential versus the alternating use of MPV and Rd.
Secondary outcome measure:
- To evaluate the response, duration of response, progression free survival (PFS), time to next therapy (TNT) and overall survival (OS) in the two different groups of patients.
- To identify, within the group of patients treated with the alternating scheme, the biological characteristics (including a comprehensive genomic analysis) of those patients resistant to one or the other, and patients refractory to both treatments
研究概览
详细说明
The Pre-treatment period includes Screening visit. After providing written informed consent form to participate in the study, patients will be evaluated for eligibility during a screening period of 14 days (Days -14 to -1). If patients meet all inclusion and exclusion criteria will be randomized at the moment of entry in the trial in a 1:1 allocation to receive either MPV followed by Rd (Treatment Group A) or MPV alternating with Rd (Treatment Group B).
Patients in the Treatment Group A will receive nine cycles of MPV consisting on one 6-weeks cycle of Velcade (Bortezomib) as an intravenous bolus twice weekly (days 1, 4, 8, 11, 22, 25, 29 and 32) followed by a 10 day rest period (day 33 to 42), in combination with oral Melphalan, once daily on days 1 to 4 and oral Prednisone, once daily on days 1 to 4, followed by eight 4-weeks cycles of Velcade (Bortezomib) as an intravenous bolus on days 1, 8, 15 and 22 followed by a 6 day rest period (days 23 to 28), in combination with Melphalan and Prednisone per os once daily on days 1 to 4, followed by a 24-day rest period (days 5 to 28). After the nine MPV cycles, patients will receive nine cycles of Rd consisting on 4-weeks cycles, including Revlimid (lenalidomide), once daily on days 1-21 followed by a 7 day rest period (days 22 to 28) plus oral dexamethasone, once weekly on days 1,8,15 and 22, followed by a 6 day rest period (days 23 to 28).
Patients in the Treatment Group B will receive the same schedule of therapy, but the MPV cycles will be alternated with Rd cycles. In this treatment Group B, patients will be again randomized to start receiving either MPV or Rd as first cycle of therapy. Overall, patients will receive an identical number of cycles, nine cycles of MPV and nine of Rd. Patients randomized to Treatment Group A relapsing/progressing or with major toxicities under treatment with MPV will be crossover to receive Rd, but only after study coordinator approval.
During the Treatment Period, patients will be evaluated at day 1 of each cycle. After completion of the Treatment Period, all patients will be evaluated every 2 months thereafter.
Safety will be assessed by the monitoring of adverse events, physical examinations, vital signs measurements, and haematology and clinical chemistry test. Response to treatment will be based on EBMT an IMWG criteria. Response to treatment will be evaluated at day 1 of each induction cycle, and every 2 months during thereafter.
研究类型
注册 (实际的)
阶段
- 阶段2
联系人和位置
学习地点
-
-
-
Alcorcón、西班牙
- Fundacion Hospital Alcorcon
-
Badalona、西班牙
- Hospital de Badalona Germans Trias i Pujol
-
Barcelona、西班牙
- Hospital Del Mar
-
Barcelona、西班牙
- Hospital de La Santa Creu i Sant Pau
-
Barcelona、西班牙
- Hospital Clinic i Provincial de Barcelona
-
Barcelona、西班牙
- H. Vall d'Hebron, Barcelona
-
Barcelona、西班牙
- ICO - Duran i Reynals, Hospitalet de Llobregat
-
Bilbao、西班牙
- Hospital De Cruces
-
Castellón、西班牙
- Hospital General de Castellon
-
Ciudad Real、西班牙
- Hospital General
-
Cuenca、西班牙
- Hospital Virgen de La Luz
-
Cáceres、西班牙
- Complejo Hospitalario de Cáceres
-
Cádiz、西班牙
- Hospital Puerta del Mar
-
Donostia、西班牙
- Hospital Donostia
-
Gandía、西班牙
- Hospital Francesc Borja
-
Girona、西班牙
- ICO - Josep Trueta
-
Guadalajara、西班牙
- Hospital General de Guadalajara
-
Jerez de la Frontera、西班牙
- H. de Jerez
-
Leon、西班牙
- Complejo Hospitalario León
-
Madrid、西班牙
- Hospital Ramon y Cajal
-
Madrid、西班牙
- Hospital La Paz
-
Madrid、西班牙
- Hospital Clinico San Carlos
-
Madrid、西班牙
- Hospital De Fuenlabrada
-
Madrid、西班牙
- Hospital Infanta Leonor
-
Madrid、西班牙
- Hospital de La Princesa
-
Madrid、西班牙
- Hospital del Tajo
-
Madrid、西班牙
- Hospital Universitario Gregorio Marañón
-
Madrid、西班牙
- Hospital Severo Ochoa
-
Madrid、西班牙
- Hospital Infanta Sofía
-
Madrid、西班牙
- Clínica Puerta de Hierro
-
Madrid、西班牙
- Hospital 12 de Octubre. Madrid
-
Madrid、西班牙
- Hospital de Madrid, S.A.- Norte Hospital General
-
Madrid、西班牙
- MD Anderson
-
Manresa、西班牙
- Althaia
-
Murcia、西班牙
- Hospital Virgen de la Arrixaca
-
Murcia、西班牙
- Hospital General Univeristario Morales Messeguer
-
Málaga、西班牙
- Complejo Hospital Costa Del Sol
-
Málaga、西班牙
- Hospital Nuestra Senora de Valme
-
Navarra、西班牙
- Hospital de la Diputación de Navarra
-
Palma de Gran Canaria、西班牙
- Hospital de Gran Canaria Doctor Negrín
-
Palma de Mallorca、西班牙
- Complejo Asistencial Son Dureta
-
Pamplona、西班牙
- Hospital Virgen del Camino
-
Sabadell、西班牙
- Corporacio Sanitaria Parc Tauli
-
Salamanca、西班牙
- Hospital Clínico de Salamanca
-
Santander、西班牙
- Hoaspital Marqués de Valdecilla
-
Santiago de Compostela、西班牙
- Complejo Hospitalario Universitario de Santiago
-
Segovia、西班牙
- Hospital General de Segovia
-
Sevilla、西班牙
- Complejo Hospitalario Regional Virgen Del Rocío
-
Tarragona、西班牙
- Hospital Joan XXIII
-
Tenerife、西班牙
- Hospital Universitario de Canarias
-
Toledo、西班牙
- Hospital Virgen de la Salud
-
Toledo、西班牙
- Hospital Nuestra Señora del Prado
-
Valencia、西班牙
- Hospital Arnau de Vilanova
-
Valencia、西班牙
- Hospital Universitario Dr. Peset
-
Valencia、西班牙
- Hospital La Fe
-
Valencia、西班牙
- Hospital Clínico de Valencia.
-
Vitoria、西班牙
- Hospital Txagorritxu
-
Zamora、西班牙
- Hospital Virgen de la Concha
-
Zaragoza、西班牙
- Hospital Clinico Lozano Blesa
-
Zaragoza、西班牙
- Miguel Servet
-
-
Baleares
-
Palma de Mallorca、Baleares、西班牙
- H. Son Llatzer
-
-
Madrid
-
Alcalá de Henares、Madrid、西班牙
- Hospital Principe de Asturias
-
-
Navarra
-
Pamplona、Navarra、西班牙
- Clinica Universitaria de Navarra
-
-
参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria:
- Written informed consent obtained before starting any study-specific procedure.
- Symptomatic elderly MM newly diagnosed by EBMT criteria older than 65 years.
- Performance status (ECOG) ≤ 2.
Have pre-treatment clinical laboratory values meeting the following criteria within 14 days of randomization:
- platelet count ≥ 75x109/L
- haemoglobin ≥ 8g/dL
- absolute neutrophil count (ANC) ≥ 1.0x109/L
- Serum bilirubin ≤ 1.5 mg/dL and alkaline phosphatise ≤ 2.5 x ULN AST, ALT ≤ 2.5 x ULN
- Serum creatinine ≤2,5 mg/dl
Exclusion Criteria:
- Patient previously received treatment with Velcade or Revlimid.
- Patient previously received treatment for Multiple Myeloma.
- Patient has ≥ Grade 2 peripheral neuropathy within 14 days before enrolment.
- Patient has hypersensitivity to bortezomib, boron, mannitol or lenalidomide.
- Patient has received other investigational drugs with 28 days before enrolment.
- Patient had a myocardial infarction within 6 months of enrolment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
- Patient currently is enrolled in another clinical research study and/or is receiving an investigational agent for any reason.
- Radiation therapy within 30 days before randomization, at least patient has had antialgic radiation. Radiation therapy will be afterwards permitted during the treatment period if it is indicated due to the presence of plasmacytomas
学习计划
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：随机化
- 介入模型：并行分配
- 屏蔽：无（打开标签）
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
|
有源比较器：MPV followed by Revlimid/Low Dose Dexamethasone (Rd)
Melphalan/Prednisone/Velcade (MPV) followed by Revlimid/Low Dose Dexamethasone (Rd)
|
|
|
实验性的：Alternating MPV with Revlimid/Low Dose Dexamethasone
Alternating Velcade/Melphalan/Prednisone (MPV) with Revlimid/Low Dose Dexamethasone (Rd)
|
研究衡量的是什么？
主要结果指标
结果测量 |
大体时间 |
|---|---|
|
To evaluate the efficacy in terms of time to progression (TTP) at 18 months of MPV and Rd used as either in a sequential or alternating approach in newly diagnosed MM patients older than 65 years.
大体时间：18 months
|
18 months
|
|
To evaluate the toxicity (safety and tolerability) of the sequential versus the alternating use of MPV and Rd,in terms of adverse events presented in both groups of patients
大体时间：6 months
|
6 months
|
次要结果测量
结果测量 |
大体时间 |
|---|---|
|
To evaluate the response in both groups of patients
大体时间：1 year
|
1 year
|
|
To identify, within the group of patients treated with the alternating scheme, the biological characteristics (including a comprehensive genomic analysis) of those patients resistant to one or the other, and patients refractory to both treatments
大体时间：2 years
|
2 years
|
|
Duration of response in two groups of patients
大体时间：2 years
|
2 years
|
|
Progression free survival (PFS) in two different groups of patients
大体时间：18 months
|
18 months
|
|
Time to next therapy (TNT)
大体时间：2 years
|
2 years
|
|
Overall survival (OS) in the two different groups of patients
大体时间：5 years
|
5 years
|
合作者和调查者
出版物和有用的链接
一般刊物
- Quwaider D, Corchete LA, Misiewicz-Krzeminska I, Sarasquete ME, Perez JJ, Krzeminski P, Puig N, Mateos MV, Garcia-Sanz R, Herrero AB, Gutierrez NC. DEPTOR maintains plasma cell differentiation and favorably affects prognosis in multiple myeloma. J Hematol Oncol. 2017 Apr 18;10(1):92. doi: 10.1186/s13045-017-0461-8.
- Paiva B, Cedena MT, Puig N, Arana P, Vidriales MB, Cordon L, Flores-Montero J, Gutierrez NC, Martin-Ramos ML, Martinez-Lopez J, Ocio EM, Hernandez MT, Teruel AI, Rosinol L, Echeveste MA, Martinez R, Gironella M, Oriol A, Cabrera C, Martin J, Bargay J, Encinas C, Gonzalez Y, Van Dongen JJ, Orfao A, Blade J, Mateos MV, Lahuerta JJ, San Miguel JF; Grupo Espanol de Mieloma/Programa para el Estudio de la Terapeutica en Hemopatias Malignas (GEM/PETHEMA) Cooperative Study Groups. Minimal residual disease monitoring and immune profiling in multiple myeloma in elderly patients. Blood. 2016 Jun 23;127(25):3165-74. doi: 10.1182/blood-2016-03-705319. Epub 2016 Apr 26.
- Paiva B, Corchete LA, Vidriales MB, Puig N, Maiso P, Rodriguez I, Alignani D, Burgos L, Sanchez ML, Barcena P, Echeveste MA, Hernandez MT, Garcia-Sanz R, Ocio EM, Oriol A, Gironella M, Palomera L, De Arriba F, Gonzalez Y, Johnson SK, Epstein J, Barlogie B, Lahuerta JJ, Blade J, Orfao A, Mateos MV, San Miguel JF; Spanish Myeloma Group / Program for the Study of Malignant Blood Diseases Therapeutics (GEM / PETHEMA) Cooperative Study Groups. Phenotypic and genomic analysis of multiple myeloma minimal residual disease tumor cells: a new model to understand chemoresistance. Blood. 2016 Apr 14;127(15):1896-906. doi: 10.1182/blood-2015-08-665679. Epub 2016 Jan 11.
研究记录日期
研究主要日期
学习开始
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (估计)
上次提交的符合 QC 标准的更新
最后验证
更多信息
与本研究相关的术语
其他相关的 MeSH 术语
其他研究编号
- GEM2010MAS65
此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.