An International, Multicenter, Open-Label Study of Vorinostat (MK0683) in Combination With Bortezomib in Patients With Relapsed or Refractory Multiple Myeloma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 143
- 主要终点
- Objective Response Rate (RR)
研究概览
简要总结
The purpose of this study is to evaluate the clinical activity of vorinostat in combination with bortezomib in participants with relapsed or refractory multiple myeloma after at least 2 prior treatment regimens. The primary objective is to define the objective response rate (RR) associated with the administration of vorinostat in combination with bortezomib to patients with relapsed and refractory multiple myeloma after at least 2 prior treatment regimens. The primary hypothesis of the study is the administration of vorinostat in combination with bortezomib will result in a clinically meaningful rate of objective response.
详细描述
The protocol has been amended to indicate that the Final Analysis is designated as the time when the primary endpoint of 29 responders has been met, or the time when all participants have discontinued treatment or have been enrolled in the study for at least 6 months (if the primary endpoint is not reached by this time). Following the Final Analysis, participants will be allowed to continue study treatment in an extension as long as they have not met the criteria for discontinuation, and will be followed for overall survival and serious AEs.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- •Has an established diagnosis of multiple myeloma based on myeloma diagnostic criteria
- •Must have adequate organ function
- •Is refractory to prior bortezomib regimen and have also been exposed to prior Immunomodulatory imide drugs (IMiD: thalidimide or lenalidmide)
- •Has relapsed and refractory multiple myeloma after at least 2 prior treatment regimens
- •Has performance status of ≤ 2 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale
- •Has measurable disease, defined as any quantifiable serum monoclonal (M) protein value and, where applicable, urine light chain of ≥200 mg/24 hours
- •Female participants are not pregnant and not breastfeeding, and are not a woman of childbearing potential (WOCBP) or are a WOCBP who agrees to follow contraceptive guidance during the treatment period and for at least 30 days after the last dose of study intervention
- •Male participants must agree to use approved contraception during the treatment period and for at least 30 days after the last dose of study intervention and refrain from donating sperm during this period
- •Is relapsed, refractory, intolerant, and/or ineligible (in the opinion of the investigator) to other therapies including an IMiD (thalidomide or lenalidomide)
- •Is refractory to bortezomib (no response on prior bortezomib containing regimen or progression on or within 60 days of bortezomib containing regimen
排除标准
- •Has known hypersensitivity to any components of bortezomib or vorinostat
- •Has had a prior allogeneic bone marrow transplant or plans to undergo any type of bone marrow transplantation within 4 weeks of the initiation of study therapy
- •Has an active systemic infection
- •Has acute diffuse infiltrative pulmonary disease or pericardial disease
- •Has known hypersensitivity to any components of bortezomib or vorinostat
- •Has active Hepatitis B or C, plasma cell leukemia, or is human immunodeficiency virus (HIV) positive
- •Has history of a prior malignancy with the exception of cervical intraepithelial neoplasia; non-melanoma skin cancer; adequately treated localized prostate carcinoma with prostate specific antigen (PSA) < 0.1; or who has undergone potentially curative therapy with no evidence of that disease for five years, or who is deemed at low risk for recurrence by his/her treating physician
- •Has known central nervous system (CNS) metastases and/or carcinomatous meningitis
- •Has plasma cell leukemia defined as the presence of more than 20% plasma cells in the peripheral blood and an absolute plasma cell count of at least 2000/μL
- •Has a history of a gastrointestinal surgery or other procedures that might, in the opinion of the Investigator, interfere with the absorption or swallowing of the study drug
- •Has preexisting National Cancer Institute (NCI) Common Toxicity Criteria (CTC) Grade 1 neuropathy with pain or >Grade 2 neuropathy
研究组 & 干预措施
Vorinostat + Bortezomib
Participants receive vorinostat 400 mg, orally, once daily (QD) on Days 1-14 of each 21-day treatment cycle and bortezomib 1.3mg/m^2 intravenous (IV) injection QD on Days 1, 4, 8 and 11 of each 21-day treatment cycle for up to 26 cycles. Participants with progressive disease (PD) after 2 cycles of treatment or no change (NC) after 4 cycles of treatment receive additional treatment of Dexamethasone, 20 mg of total daily dose, orally on Days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day treatment cycle for up to 26 cycles. Eligible participants could receive additional treatment on an extension.
干预措施: Vorinostat (Drug)
Vorinostat + Bortezomib
Participants receive vorinostat 400 mg, orally, once daily (QD) on Days 1-14 of each 21-day treatment cycle and bortezomib 1.3mg/m^2 intravenous (IV) injection QD on Days 1, 4, 8 and 11 of each 21-day treatment cycle for up to 26 cycles. Participants with progressive disease (PD) after 2 cycles of treatment or no change (NC) after 4 cycles of treatment receive additional treatment of Dexamethasone, 20 mg of total daily dose, orally on Days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day treatment cycle for up to 26 cycles. Eligible participants could receive additional treatment on an extension.
干预措施: Bortezomib (Drug)
Vorinostat + Bortezomib
Participants receive vorinostat 400 mg, orally, once daily (QD) on Days 1-14 of each 21-day treatment cycle and bortezomib 1.3mg/m^2 intravenous (IV) injection QD on Days 1, 4, 8 and 11 of each 21-day treatment cycle for up to 26 cycles. Participants with progressive disease (PD) after 2 cycles of treatment or no change (NC) after 4 cycles of treatment receive additional treatment of Dexamethasone, 20 mg of total daily dose, orally on Days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day treatment cycle for up to 26 cycles. Eligible participants could receive additional treatment on an extension.
干预措施: Dexamethasone (Drug)
结局指标
主要结局
Objective Response Rate (RR)
时间窗: Up to approximately 30 months (through Final Analysis data cut-off of 16-May-2011)
Objective RR was defined as percentage (%) of participants with complete response (CR: disappearance of original monoclonal (M) paraprotein from blood \& urine on at least 2 determinations for at least 6 weeks (WKs) by immunofixation studies, \<5% plasma cells in bone marrow on at least 1 determination, no increase in size/number of lytic bone lesions (LBLs) \& disappearance of soft tissue plasmacytomas (STP) for at least 6 WKs on skeletal survey (SS) if available) or partial response (PR: ≥50% reduction in serum M protein for at least 2 determinations 6 WKs apart, if present, reduction in 24-hour urinary light chain excretion by ≥90% or ≤200 mg for at least 2 determinations 6 WKs apart, ≥50% reduction in STP size for at least 6 WKs, \& no increase in size/number of LBLs on SS if available) as assessed by Independent Adjudication Committee (IAC) per European Blood \& Marrow Transplant (EBMT) criteria. To report RR \& 95% confidence intervals (CIs), exact test of binomial parameter was used.
次要结局
- Time To Disease Progression (TTP) as Determined by IAC Per EBMT Criteria(Up to approximately 30 months (through Final Analysis data cut-off of 16-May-2011))
- Number of Participants Who Experienced an Adverse Event (AE)(Up to approximately 22 months)
- Number of Participants Who Discontinued Study Treatment Due to an AE(Up to approximately 18 months)
- TTP as Assessed by Investigator Per EBMT Criteria(Up to approximately 30 months (through Final Analysis data cut-off of 16-May-2011))
- Progression-Free Survival (PFS) as Determined by IAC Per EBMT Criteria(Up to approximately 30 months (through Final Analysis data cut-off of 16-May-2011))
- PFS as Assessed by Investigator Per EBMT Criteria(Up to approximately 30 months (through Final Analysis data cut-off of 16-May-2011))
- Overall Survival (OS)(Up to approximately 40 months (through End of Trial data cut-off of 09-Apr-2012))