Phase I Study of Plitidepsin (Aplidin®) in Combination With Bortezomib and Dexamethasone in Patients With Relapsed and/or Refractory Multiple Myeloma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 39
- 试验地点
- 7
- 主要终点
- Recommended Dose of Bortezomib in Combination With Plitidepsin and Dexamethasone
研究概览
简要总结
Study of Plitidepsin (Aplidin®) to determine the recommended dose (RD) of plitidepsin in Combination with Bortezomib and Dexamethasone in Patients with Relapsed and/or Refractory Multiple Myeloma.
详细描述
Phase I Multicenter, Open-label, Dose-escalating Clinical and Pharmacokinetic Trial of Plitidepsin (Aplidin®) to determine the recommended dose (RD) of plitidepsin in combination with bortezomib and dexamethasone in patients with relapsed and/or refractory multiple myeloma (MM), to determine the efficacy of the combination plitidepsin/bortezomib/dexamethasone, to evaluate the safety and tolerability of the combination in patients with relapsing and/or refractory MM and to study the pharmacokinetics (PK) and pharmacodynamics (PDy) of plitidepsin in combination with bortezomib and dexamethasone.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 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
- •Age ≥ 18 years.
- •Prior autologous transplantation (HSCT) patients are allowed.
- •Patients must have received at least one previous treatment line of induction, chemotherapy, chemotherapy and transplantation or previous treatment with bortezomib or another proteasome drug
排除标准
- •Previous treatment with plitidepsin.
- •Active or metastatic primary malignancy other than MM.
- •Serious concomitant systemic disorders
- •History of hypersensitivity reactions to bortezomib, polyoxyl 35 castor oil or mannitol
- •Neuropathy
- •Pregnant and/or lactating women
- •HIV infection
- •Active hepatitis B or C virus infection.
- •Treatment with any Investigational Medicinal Product (IMP) in the 30 days before inclusion in the study
- •Plasma cell leukemia at the time of study entry
- •Contraindication for the use of steroids
研究组 & 干预措施
plitidepsin + bortezomib + dexamethasone
Plitidepsin will be administered as a 3-hour (h) intravenous (i.v.) infusion on Day (D) 1 and 15, every four weeks (q4wk).
Bortezomib will be administered as a subcutaneous (s.c.) injection on D1, 4, 8 and 11, q4wk, for a maximum of eight cycles.
Dexamethasone will be taken orally on D1, 8, 15 and 22, q4wk
干预措施: Plitidepsin (Drug)
plitidepsin + bortezomib + dexamethasone
Plitidepsin will be administered as a 3-hour (h) intravenous (i.v.) infusion on Day (D) 1 and 15, every four weeks (q4wk).
Bortezomib will be administered as a subcutaneous (s.c.) injection on D1, 4, 8 and 11, q4wk, for a maximum of eight cycles.
Dexamethasone will be taken orally on D1, 8, 15 and 22, q4wk
干预措施: Bortezomib (Drug)
plitidepsin + bortezomib + dexamethasone
Plitidepsin will be administered as a 3-hour (h) intravenous (i.v.) infusion on Day (D) 1 and 15, every four weeks (q4wk).
Bortezomib will be administered as a subcutaneous (s.c.) injection on D1, 4, 8 and 11, q4wk, for a maximum of eight cycles.
Dexamethasone will be taken orally on D1, 8, 15 and 22, q4wk
干预措施: Dexamethasone (Drug)
结局指标
主要结局
Recommended Dose of Bortezomib in Combination With Plitidepsin and Dexamethasone
时间窗: After 28-day cycle
To determine the recommended dose (RD) of plitidepsin in combination with bortezomib and dexamethasone in patients with relapsed and/or refractory multiple myeloma (MM). To define the RD, patients will be evaluated for DLTs during the first 28-day cycle. The RD will be the highest DL at which fewer than two out of six (33%) of evaluable patients experience a DLT during the first 28-day cycle.
Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)
时间窗: After 28-day cycle
DLTs were defined as: Hematological Toxicity * Grade 3/4 neutropenia associated with fever or lasting\>7 days related to the study treatment * Grade 3/4 thrombocytopenia accompanied by grade 3/4 hemorrhage * Extensive bone marrow (BM) infiltration, DLT was defined as grade 4 thrombocytopenia with grade 3/4 hemorrhage or grade 4 neutropenia lasting \>7 days or with fever Non-hematological Toxicity * Grade 3/4 nausea and vomiting refractory to antiemetic therapy * Grade≥3 muscular Adverse events (AE) (myalgia, muscular weakness, muscle cramps, myopathy) * Grade≥3 alanine aminotransferase (ALT)/Aspartate aminotransferase (AST) lasting more than 1 week * Grade≥3 bilirubin increase * Grade≥3 creatine phosphokinase (CPK) increase * Cardiac toxicity * Symptomatic or treatment-requiring grade ≥1 cardiac arrhythmia related to plitidepsin * Grade≥1 left ventricular systolic dysfunction related to plitidepsin * Neuropathic pain and peripheral sensory neuropathy related to BTZ
Recommended Dose of Plitidepsin in Combination With Bortezomib and Dexamethasone
时间窗: After 28-day cycle
To determine the recommended dose (RD) of plitidepsin in combination with bortezomib and dexamethasone in patients with relapsed and/or refractory multiple myeloma (MM). To define the RD, patients will be evaluated for DLTs during the first 28-day cycle. The RD will be the highest DL at which fewer than two out of six (33%) of evaluable patients experience a DLT during the first 28-day cycle.
Recommended Dose of Dexamethasone in Combination With Plitidepsin and Bortezomib
时间窗: After 28-day cycle
To determine the recommended dose (RD) of plitidepsin in combination with bortezomib and dexamethasone in patients with relapsed and/or refractory multiple myeloma (MM). To define the RD, patients will be evaluated for DLTs during the first 28-day cycle. The RD will be the highest DL at which fewer than two out of six (33%) of evaluable patients experience a DLT during the first 28-day cycle.
次要结局
- Overall Response Rate(Response or disease progression was assessed on Day 1 of each cycle, assessed up to 4 years)
- Time to Progression(From the date of the first infusion to the date of documented PD or death due to PD, up to 4 years)
- Event-free Survival(From the date of first infusion to the date of documented PD or death, up to 4 years)
- Event-free Survival Rates(from the date of first infusion to the date of documented PD or death, up to 4 years)
- Progression-free Survival(from the date of the first infusion to the date of documented PD or death, up to 4 years)
- Progression-free Survival Rates(From the date of the first infusion to the date of documented PD or death, up to 4 years)
- Response According to International Myeloma Working Group Criteria(Response or disease progression was assessed on Day 1 of each cycle, assessed up to 4 years)
- Duration of Response(From the date of the first documentation of response to the date of PD or further therapy or death, up to 4 years)
- Time to Progression Rates(From the date of the first infusion to the date of documented PD or death due to PD, up to 4 years)