Phase II High Pulse Dose Clinical Trial of Orally Administered ITF2357 In Patients With Relapsed/Refractory Multiple Myeloma
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 1
- 试验地点
- 1
- 主要终点
- Number of patients with relapsing/refractory multiple myeloma with TEAE, included serious AE
研究概览
简要总结
Primary objective:
To assess the safety of ITF 2357 administered once weekly at high pulse dose in patients with relapsing/refractory multiple myeloma.
Secondary objectives:
- To evaluate the anti-tumour activity of ITF 2357 administered once weekly at high pulse dose in patients with advanced multiple myeloma, measured as decrease of M protein.
- To assess the therapeutic response to ITF3257 according to EBMT criteria.
- To determine pharmacokinetic profile of ITF 2357 administered following high pulse dose schedule.
详细描述
This is open label, phase IIa High Pulse Dose Clinical Trial testing ITF2357 (orally administered) in adult patients with relapsing/refractory multiple myeloma after at least 2 previous lines of treatment.
Patients are planned to receive ITF2357 in accordance with following scheme:
Weeks 1-6
Patient #01 is planned to receive ITF 2357 at 400 mg in one single dose on day 1, 8, 15, 22, 29 and 36. Safety assessments are planned to be performed twice a week. If no issue (grade >3 neutropenia or any other grade ≥3 toxicity) emerges at day 15, two further patients (#02 and #03) will be enrolled and receive the same dose. If patients #02 and #03 show a favourable safety profile at day 15, and in the meantime no safety concerns arise from patient #01, the further patients will be enrolled and treated according to the below reported scheme:
- 8 more patients (#04-11) will receive 400 mg once weekly; safety assessments will be performed weekly.
- 1 patient (#12) will receive 600 mg once weekly; safety assessments will be performed twice a week.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
盲法说明
This was an open label
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
- •Established diagnosis of multiple myeloma according to International Myeloma Working Group diagnostic criteria
- •Age ≥ 18 years
- •Patient relapsed after at least 2 lines of conventional chemotherapy or high dose therapy with autologous or allogeneic stem cell support, and/or for whom no alternative treatments are available/suitable
- •Increasing trend of monoclonal immunoglobulin or Bence-Jones proteinuria through the last 4 consecutive pre-screening measurements, already available in the patient history
- •No chemotherapy or other investigational anticancer therapy for at least 3 weeks before the start of the study
- •Full recovery from previous toxicities
- •ECOG performance status 0-2
- •Adequate bone marrow reserve: absolute neutrophil count ≥ 1000/ml; platelet count ≥ 90000/ml
- •Adequate liver function: total bilirubin within normal institutional limits (PI center); AST(SGOT)/ALT(SGPT) ≤ 2.5 x institutional upper limit of normal (PI center)
- •Adequate renal function: Creatinine ≤ 2.5 mg/dl or creatinine clearance ≥ 50 ml/min
- •Either men or women, accepting to practice effective contraception during the entire study period unless documentation of infertility exists. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should immediately inform her treating physician; in this case ITF 2357 treatment will be promptly discontinued
- •Able to understand and willing to sign the informed consent form.
排除标准
- •Planned autologous or allogeneic bone marrow transplantation within 4 weeks of the initiation of ITF 2357 administration
- •Concurrent use of medicines that would confound the interpretation of toxicities and anti-tumour activity of ITF 2357 (i.e. quinolones, macrolides, 5-HT3 antagonists except for palonosetron,)
- •Clinically significant illness including, but not limited to, the following: active infection, uncontrolled hypertension, symptomatic congestive heart failure, unstable angina pectoris, myocardial infarction within the past 6 months, cardiac arrhythmia (present or documented in the past, of any kind), any other condition (including laboratory abnormalities) that in the opinion of the Investigator places the patient to unacceptable risk for adverse outcome if he/she were to participate in the study
- •Psychiatric illness/social situations that would limit compliance with study medication and protocol requirements
- •Pregnant or lactating women
- •Positive blood tests for HIV, HBV, HCV, active EBV and CMV
- •Diseases related to active viral infections
- •Patients with a marked baseline prolongation of QTc interval (e.g. repeated demonstration of a QTc interval >440 ms for men and >450 ms for women)
- •Patients with history of additional risk factors for Torsade de Pointes (e.g. heart failure, family history of Long QT Syndrome).
- •The use of concomitant medications with potential risk of Torsade de Pointes and/or that can prolong QTc interval
研究组 & 干预措施
ITF2357
Eligible patients had to be treated with weekly single doses of ITF2357 according to the above mentioned treatment plan.
干预措施: ITF2357 (Drug)
结局指标
主要结局
Number of patients with relapsing/refractory multiple myeloma with TEAE, included serious AE
时间窗: 30 weeks
Number of patients with TEAE, included serious AE, was assessed while receiving once weekly ITF2357 at high pulse dose.
次要结局
- Decrease in M protein and clinical response rate (PR plus CR according to the European Group for Blood & Marrow Transplantation - EBMT- criteria).(18 weeks)