A Study of Oral Ixazomib Maintenance Therapy in Participants With Newly Diagnosed Multiple Myeloma (NDMM) Not Treated With Stem Cell Transplantation (SCT)
- Conditions
- Multiple Myeloma
- Registration Number
- JPRN-jRCT2080222821
- Lead Sponsor
- Takeda Pharmaceutical Company Limited
- Brief Summary
In conclusion, the novel design of Study C16021 showed that, regardless of a patient's frontline induction regimen, ixazomib maintenance therapy significantly prolonged PFS as compared with placebo among patients with NDMM who were ineligible for SCT. With demonstrated efficacy, safety, convenience, maintenance of HRQOL, no increase in health care resources, and an alternative mechanism of action, ixazomib remains a valuable maintenance treatment option for these patients.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- completed
- Sex
- All
- Target Recruitment
- 706
1. Adult male or female participants 18 years or older with a confirmed diagnosis of symptomatic NDMM according to standard criteria.
2. Completed 6 to 12 months (plus/minus 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.
3. 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.
4. 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 (eg, calendar, ovulation, symptothermal, postovulation methods] and withdrawal are not acceptable methods of contraception.)
Male participants, even if surgically sterilized (that is, 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 [eg, calendar, ovulation, symptothermal, postovulation methods for the female partner] and withdrawal are not acceptable methods of contraception.)
5. 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.
6. Complete documentation of the details of the initial therapy before randomization including cytogenetics and International Staging System (ISS) is available.
7. Eastern Cooperative Oncology Group Performance Status of 0 to 2.
8. Suitable venous access for the study-required blood sampling and consent for the specific amounts that will be taken.
9. Is willing and able to adhere to the study visit schedule and other protocol requirements including blood sampling and bone marrow aspiration.
10. 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^3. Platelet transfusions to help participants meet eligibility criteria are not allowed within 3 days before randomization.
- Total bilirubin =< 1.5 x the upper limit of the normal range (ULN).
- Alanine aminotransferase and aspartate aminotransferase =< 3 x ULN.
- Calculated creatinine clearance >= 30 mL/min (using the Cockcroft-Gault equation).
1. Multiple myeloma that has relapsed after, or was not responsive to, initial therapy.
2. Prior stem-cell transplantation (SCT).
3. Radiotherapy within 14 days before randomization.
4. Diagnosed or treated for another malignancy within 5 years before randomization or previous diagnosis with another malignancy. Participants with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
5. Female participants who are lactating and breastfeeding or have a positive serum pregnancy test during the Screening period.
6. Major surgery within 14 days before randomization.
7. Central nervous system involvement.
8. Infection requiring intravenous (IV) antibiotic therapy or other serious infection within 14 days before randomization.
9. Diagnosis of Waldenstrom's macroglobulinemia, POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome, plasma cell leukemia, primary amyloidosis, myelodysplastic syndrome, or myeloproliferative syndrome.
10. 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.
11. Systemic treatment with strong cytochrome P450 3A (CYP3A) inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital) or use of Ginkgo biloba or St. John's wort within 14 days before randomization.
12. Ongoing or active infection, known human immunodeficiency virus (HIV) positive, active hepatitis B or C infection.
13. 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 (eg, peripheral neuropathy (PN) that is Grade 1 with pain or Grade 2 or higher of any cause).
14.Psychiatric illness or social situation that would limit compliance with study requirements.
15.Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent.
16.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.
17.Treatment with any investigational products within 30 days before randomization.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method efficacy<br>PFS<br>Timeframe: From randomization PD or death<br>PFS is defined as the time from the date of randomization to the date of first documentation of PD or death from any cause, as evaluated by an independent review committee (IRC) according to International Myeloma Working Group (IMWG) criteria, or death due to any cause, whichever occurs first. Per IMWG criteria, PD: serum M-component increase >=0.5 g/dl or urine M-component increase >=200 mg/24-hour/ difference between involved and uninvolved FLC levels increase >10 mg/dl or bone marrow plasma cell >=10%/ development of new/ increase in size of existing bone lesions or soft tissue plasmacytoma or development of hypercalcemia (corrected serum calcium >11.5mg/dL).
- Secondary Outcome Measures
Name Time Method