China Continuation: A Single-Arm, Open-Label Study of Oral Ixazomib Maintenance Therapy After Initial Therapy in Patients With Newly Diagnosed Multiple Myeloma Not Treated With Stem Cell Transplantation
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 37
- 试验地点
- 10
- 主要终点
- Number of Participants Categorized According to Performance Status (PS) Based on Eastern Cooperative Oncology Group (ECOG) PS
研究概览
简要总结
The purpose of this study is to determine the long-term safety and tolerability of ixazomib maintenance therapy.
详细描述
The drug being tested in this study is called ixazomib. Ixazomib is being tested to slow disease progression and improve overall survival in Chinese participants who have newly diagnosed multiple myeloma (NDMM) who have had a major positive response to initial therapy and have not undergone stem cell transplantation (SCT). This study will look at the effect of ixazomib has on the length of time that participants are free of disease progression and their overall survival. After the implementation of Amendment 8, participants who received placebo-matching capsules before unblinding and have not yet experienced disease progression will cross over to receive ixazomib.
The study will enroll approximately 37 patients. Participants will be assigned to a single treatment group
• Ixazomib
All participants will be asked to take one capsule on Days 1, 8, and 15 of every 28-day cycle, for up to approximately 24 months (equivalent to 26 cycles [if no cycle delays], to the nearest complete cycle) or until documented progressive disease (PD) or intolerable toxicity, whichever occurs first.
This multi-center trial will be conducted in China. The overall time to participate in this study is until a total of approximately up to 60 months. Participants will make multiple visits to the clinic, and every 4 weeks until the next line of therapy begins for a follow-up assessment.
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
- •Adult male or female participants aged 18 years or older with a confirmed diagnosis of symptomatic NDMM according to standard criteria.
- •Has completed 6 to 12 months (±2 weeks) of initial therapy, during which the participant was treated to best response, defined as the best response maintained for 2 cycles after the M-protein nadir is reached.
- •Has documented major response (partial response [PR], very good partial response [VGPR], complete response [CR]) according to the international myeloma working group (IMWG) uniform response criteria, version 2011, after this initial therapy.
- •Female participants who:
- •Are postmenopausal for at least 1 year before the screening visit, OR Are surgically sterile, OR If they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent through 90 days after the last dose of study drug, or Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the participant. (Periodic abstinence [e.g., calendar, ovulation,symptothermal, postovulation methods] and withdrawal are not acceptable methods of contraception.)
- •Male participants, even if surgically sterilized (i.e., status postvasectomy), who:
- •Agree to practice effective barrier contraception during the entire study Treatment period and through 90 days after the last dose of study drug, or Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the participant. (Periodic abstinence [e.g., calendar, ovulation, symptothermal, postovulation methods for the female partner] and withdrawal are not acceptable methods of contraception.)
- •Voluntary written consent must be given before performance of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the participant at any time without prejudice to future medical care.
- •Has availability of complete documentation for:
- •Details of initial disease state, initial therapy, and response
- •Cytogenetic assessment at diagnosis (cytogenetic assessment performed after diagnosis must be approved by a Takeda project clinician or designee)
- •International Staging System (ISS) staging at diagnosis (requiring beta 2-microglobulin and serum albumin results).
- •Has Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to
- •Suitable venous access for the study-required blood sampling and consent for the specific amounts that will be taken.
- •Participant is willing and able to adhere to the study visit schedule and other protocol requirements including blood sampling and bone marrow aspiration.
- •Participants must meet the following clinical laboratory criteria at study entry:
- •Absolute neutrophil count (ANC) ≥1,000/mm^3 without growth factor support and platelet count ≥ 75,000/mm^
- •Platelet transfusions to help participants meet eligibility criteria are not allowed within 3 days before enrollment.
- •Total bilirubin ≤1.5*the upper limit of the normal range (ULN).
- •Alanine aminotransferase and aspartate aminotransferase ≤3*ULN.
- •Calculated creatinine clearance ≥30 mL/min (using the Cockroft-Gault equation).
排除标准
- •Has multiple myeloma that relapsed after, or was not responsive to, initial therapy.
- •Had prior stem-cell transplantation (SCT).
- •Has radiotherapy within 14 days before enrollment.
- •Had been diagnosed or treated for another malignancy within 5 years before enrollment or previously diagnosed with another malignancy with evidence of residual disease. Participants with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
- •Female participants who are lactating and breastfeeding or have a positive serum pregnancy test during the Screening period.
- •Has major surgery within 14 days before enrollment.
- •Has central nervous system involvement.
- •Infection requiring intravenous (IV) antibiotic therapy or other serious infection within 14 days before enrollment.
- •Has diagnosis of Waldenstrom's macroglobulinemia, polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome, plasma cell leukemia, primary amyloidosis, myelodysplastic syndrome, or myeloproliferative syndrome.
- •Evidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, uncontrolled congestive heart failure, unstable angina, or myocardial infarction within the past 6 months.
- •Systemic treatment with strong cytochrome P450 (CYP3A) inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital) or use of St. John's wort within 14 days before enrollment.
- •Ongoing or active infection, known human immunodeficiency virus positive, active hepatitis B or C infection.
- •Has comorbid systemic illnesses or other severe concurrent disease that, in the judgment of the investigator, would make the participant inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens (e.g., peripheral neuropathy (PN) that is Grade 1 with pain or Grade 2 or higher of any cause).
- •Psychiatric illness/social situation that would limit compliance with study requirements.
- •Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent.
- •Inability to swallow oral medication, inability or unwillingness to comply with the drug administration requirements, or gastrointestinal (GI) procedure that could interfere with the oral absorption or tolerance of treatment.
- •Treatment with any investigational products within 30 days before enrollment.
研究组 & 干预措施
Ixazomib
Participants received ixazomib 3 milligrams (mg), capsules, orally, once on Days 1, 8, and 15 for Cycles 1 through 4, during which if the participants tolerated the initial dose, the dose was escalated to ixazomib 4 mg, capsules, orally, once on Days 1, 8, and 15 for Cycles 5 through 26, or until documented PD or intolerable toxicity, whichever occurred first (cycle length=28 days).
干预措施: Ixazomib (Drug)
结局指标
主要结局
Number of Participants Categorized According to Performance Status (PS) Based on Eastern Cooperative Oncology Group (ECOG) PS
时间窗: Month 25
ECOG PS was used to assess physical health of participants. ECOG PS grade:0= fully active, able to carry on all pre-disease performance without restriction,1= restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature 2= ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours, 3= capable of only limited self-care, 4= completely disabled, cannot carry on any selfcare, totally confined to bed or chair confined to bed or chair more than 50% of waking hours and 5= dead. Only those categories with non-zero values were reported.
Percentage of Participants Receiving Ixazomib With Treatment-emergent Adverse Events (TEAEs)
时间窗: Up to 58.4 months
Adverse events (AEs) were defined as any unfavorable and unintended sign, symptom or disease temporally associated with the use of a medicinal product reported from first dose of study drug through 30 days after the last dose of study drug. A TEAE was defined as an AE that started or worsened after first study drug administration and within 30 days of last dose of study drug. Percentages are rounded off to the nearest whole number.
Percentage of Participants Receiving Ixazomib With Treatment-emergent Serious Adverse Events (SAEs)
时间窗: Up to 58.4 months
AEs were defined as any unfavorable and unintended sign, symptom or disease temporally associated with the use of a medicinal product reported from first dose of study drug through 30 days after the last dose of study drug. A TEAE was defined as an AE that started or worsened after first study drug administration and within 30 days of last dose of study drug. An SAE was defined as any untoward medical occurrence that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability or incapacity, was a congenital abnormality or birth defect, or is an important medical event. Percentages are rounded off to the nearest whole number.
Number of Participants Receiving Ixazomib With Clinically Significant Changes in Safety Laboratory Values
时间窗: Up to 58.4 months
Clinical laboratory assessments included hematology, serum chemistry, and urinalysis. Any clinically significant changes in the clinical laboratory value over time based on the investigator's interpretation were reported.
次要结局
- Progression-Free Survival (PFS)(From the first dose of study drug to every 4 weeks until PD or death from any cause (up to 58.4 months))
- Overall Survival (OS)(From the first dose of study drug to every 12 weeks during follow-up after PD or next line therapy or death whichever occurred later (up to 58.4 months))
- Percentage of Participants Who Achieved or Maintained Best Response Before PD or up to Subsequent Therapy(Up to 58.4 months)
- Duration of Complete Response (CR)(Up to 58.4 months)
- Time to Progression (TTP)(Up to 58.4 months)
- Time to Next-Line Therapy (TTNT)(Up to 58.4 months)
- Percentage of Participants With A New Primary Malignancy(Up to 58.4 months)
- Change From Baseline in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 as Measured by the Global Health Status (GHS)(Baseline, Cycle 26 (cycle length=28 days))
- Correlation Between Frailty Status and PFS(Up to 58.4 months)
- Correlation Between Frailty Status and OS(Up to 58.4 months)
- Plasma Concentration of Ixazomib(Cycle 1 (1 and 4 hours post-dose Day 1, Days 8 and 15 pre-dose); Cycle 2 and 5 (Days 1 and 8 pre-dose) and Cycles 3, 4, 6 to 10 (Day 1 pre-dose) (cycle length=28 days))
- Time to Resolution of Peripheral Neuropathy (PN) Events(Up to 58.4 months)
- Time to Improvement of PN Events(Up to 58.4 months)