Nelfinavir as Bortezomib-sensitizing Drug in Patients With Proteasome Inhibitor-nonresponsive Myeloma. A Multicenter Phase II Trial
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 34
- 试验地点
- 12
- 主要终点
- Response rate based on best response observed during the trial
研究概览
简要总结
Trial objectives:
To decide whether the addition of nelfinavir to the approved antimyeloma therapy with bortezomib and dexamethasone has sufficient activity in proteasome inhibitor-resistant myeloma patients to merit further clinical investigation in a prospective controlled trial.
Additional research questions:
To collect myeloma cell samples from proteasome inhibitor-resistant myeloma patients for the assessment of the biology of proteasome inhibitor resistance and the identification of predictive markers for response to nelfinavir-based antimyeloma therapy.
详细描述
Trial objectives:
To decide whether the addition of nelfinavir to the approved antimyeloma therapy with bortezomib and dexamethasone has sufficient activity in proteasome inhibitor-resistant myeloma patients to merit further clinical investigation in a prospective controlled trial.
Additional research questions:
To collect myeloma cell samples from proteasome inhibitor-resistant myeloma patients for the assessment of the biology of proteasome inhibitor resistance and the identification of predictive markers for response to nelfinavir-based antimyeloma therapy.
Primary endpoint:
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
- •Patient must give written informed consent prior to any protocol-specific procedure.
- •Patient was diagnosed with multiple myeloma based on standard IMWG criteria, and has received at least one previous line of chemotherapy.
- •Patient has been exposed to or is intolerant to at least one IMID (thalidomide, lenalidomide, pomalidomide).
- •A therapy with bortezomib in the approved dose and schedule, based on Swissmedic approval (treatment of patients with relapsed/refractory multiple myeloma who have received at least one prior line of therapy), is indicated and intended.
- •Patient is refractory to his/her most recent proteasome inhibitor-containing regimen, based on divers criteria.
- •WHO performance status ≤
- •Age ≥ 18 years.
- •Adequate hematological values: platelets ≥ 50 x 109/L, hemoglobin ≥ 80 g/L (both may be achieved by transfusion).
- •Adequate hepatic function: bilirubin ≤ 1.5 x ULN (for patients with suspected hemolysis: direct bilirubin ≤ 1.5 x ULN), ALT ≤ 3 x ULN (≤ 5 x ULN if liver infiltration by myeloma suspected, based on imaging results).
- •Calculated creatinine clearance ≥ 15 mL/min, according to the formula of Cockcroft-Gault, see Appendix 1).
- •Women are not breastfeeding. Women with child-bearing potential are using effective contraception (see 9.8), are not pregnant and agree not to become pregnant during participation in the trial and during the 12 months thereafter. A negative pregnancy test before inclusion (within 7 days) into the trial is required for all women with child-bearing potential. Men agree not to father a child during participation in the trial and during 12 months thereafter.
- •Completed baseline QoL questionnaire.
排除标准
- •Evidence of ongoing uncontrolled systemic infections.
- •History of chronic active HCV or HBV.
- •Evidence of myeloma within the CNS.
- •Psychiatric disorder precluding understanding of information on trial related topics, giving informed consent, filling out quality of life (QoL) forms, or interfering with compliance for oral drug intake.
- •Exposure to another experimental drug within 3 weeks prior to trial entry.
- •Any serious underlying medical condition (at the judgment of the investigator) which may impair the ability of the patient to participate in the trial, in particular any uncontrolled clinically significant active disease (e.g. active autoimmune disease, uncontrolled diabetes, uncontrolled cardiac disease).
- •Non-hematologic active malignancy within the past 5 years with the exception of a) adequately treated basal cell carcinoma, squamous cell skin cancer, or thyroid cancer; b) carcinoma in situ of the cervix or breast; c) prostate cancer of Gleason Grade 6 or less with stable prostate-specific antigen levels; or d) cancer considered cured by surgical resection or unlikely to impact survival during the duration of the study, such as localized transitional cell carcinoma of the bladder or benign tumors of the adrenal or pancreas.
- •Concomitant use of other anti-cancer medication or radiotherapy except for local pain control. The use of bisphosphonates is allowed.
- •Significant neuropathy (Grades 3-4, or Grade 2 with pain) within 14 days prior to enrollment.
- •Known hypersensitivity to bortezomib or nelfinavir or hypersensitivity to components of these drugs.
- •Any psychological, familial, sociological or geographical condition likely hampering compliance with the trial protocol and follow-up.
- •Patient who takes the following drugs during the trial therapy, which cannot be replaced or paused.
研究组 & 干预措施
Nelfinavir, Bortezomib, Dexamethasone
The trial is designed as an "add-on" therapy, where nelfinavir is added to the approved bortezomib-containing therapy. Bortezomib and dexamethasone background treatment will be given in the Swissmedic-approved dose and schedule and according to international therapeutic standard.
干预措施: Nelfinavir (Drug)
Nelfinavir, Bortezomib, Dexamethasone
The trial is designed as an "add-on" therapy, where nelfinavir is added to the approved bortezomib-containing therapy. Bortezomib and dexamethasone background treatment will be given in the Swissmedic-approved dose and schedule and according to international therapeutic standard.
干预措施: bortezomib (Drug)
Nelfinavir, Bortezomib, Dexamethasone
The trial is designed as an "add-on" therapy, where nelfinavir is added to the approved bortezomib-containing therapy. Bortezomib and dexamethasone background treatment will be given in the Swissmedic-approved dose and schedule and according to international therapeutic standard.
干预措施: Dexamethasone (Drug)
结局指标
主要结局
Response rate based on best response observed during the trial
时间窗: end of cycle 6 (at week 19)
次要结局
- Adverse events(end of cycle 6 (at week 19))
- Proportion of patients achieving at least a minor response(end of cycle 6 (at week 19))
- Disease control rate (no evidence of disease progression for at least 3 cycles)(end of cycle 6 (at week 19))
- Time from registration to the start of the next new antimyeloma therapy or death from any cause(end of cycle 6 (at week 19))
- Progressive disease under trial treatment(end of cycle 6 (at week 19))
- Quality of life(day 1 of cycle 4 (week 10))