Multiple Myeloma, Autologous Stem Cell Transplant
Conditions
Interventions
investigational material(s)
Generic name etc : Ixazomib Citrate
INN of investigational material : Ixazomib
Therapeutic category code : 429 Other antitumor agents
Dosage and Administration for Investi
Sponsors
Takeda Pharmaceutical Company Limited
Millennium Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Adult male or female participants 18 years or older with a confirmed diagnosis of symptomatic multiple myeloma according to standard criteria. 2. Documented results of cytogenetics/ fluorescence in situ hybridization (FISH) obtained at any time before transplant, and International Staging System (ISS) staging at the time of diagnosis available. 3. Underwent standard of care induction therapy (induction therapy must include proteasome inhibitor (PI) and/or immunomodulating drugs (IMiD)-based regimens as primary therapy for multiple myeloma), followed by a single autologous stem cell transplant (ASCT) with a high-dose melphalan (200 mg/m^2) conditioning regimen, within 12 months of diagnosis. Vincristine, Adriamycin [doxorubicin], and dexamethasone (VAD) is not an acceptable induction therapy for this trial. 4. Started screening no earlier than 75 days after transplant, completed screening within 15 days, and randomized no later than 115 days after transplant. 5. Must have not received post-ASCT consolidation therapy. 6. Documented response to ASCT (partial response [PR], very good partial response [VGPR], complete response [CR]/stringent complete response [sCR]) according to International Myeloma Working Group (IMWG) criteria. 7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. 8. Female participants who: - 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, AND - Must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable, 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.) Male participants, even if surgically sterilized (ie, 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, AND - Must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable, 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.) 9. 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. 10. Suitable venous access for the study-required blood sampling. 11. Is willing and able to adhere to the study visit schedule and other protocol requirements. 12. Must meet the following clinical laboratory criteria at study entry: - Absolute neutrophil count (ANC) >= 1,000/ per cubic milliliter (mm^3) 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 (ALT) and aspartate aminotransferase (AST) <= 3 x ULN. - Calculated creatinine clearanc
Exclusion criteria
Exclusion criteria: 1. Multiple myeloma which has relapsed following primary therapy or is not responsive to primary therapy. For this study, stable disease following ASCT will be considered nonresponsive to primary therapy. 2. Double (tandem) ASCT. 3. Radiotherapy within 14 days before the first dose of study drug. 4. Diagnosed or treated for another malignancy within 5 years before randomization 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. 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, symptomatic 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 in the study. 12. Active hepatitis B or C virus infection, or known human immunodeficiency virus (HIV) positive. 13. Comorbid systemic illnesses or other severe concurrent disease which, 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 that is Grade 1 with pain or Grade 2 or higher of any cause). 14. Psychiatric illness/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 60 days before the first dose of the study drug regimen.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| efficacy Progression Free Survival (PFS) Time Frame: Randomization up to End of treatment (EOT) (24 months); thereafter followed up every 4 weeks until progression of disease or death (up to 4 years) PFS was defined as the time from the date of randomization to the date of first documentation of progressive disease (PD), as evaluated by an independent review committee (IRC) according to International Myeloma Working Group (IMWG) criteria, or death due to any cause, whichever occured first. PD was defined as >=25% increase from lowest value in: serum/urine M-component; participants without measurable serum and urine M-protein levels, the difference between involved and uninvolved free light chain (FLC) levels must have been >10 mg/dL; participants without measurable serum, urine M-protein levels and FLC levels, bone marrow plasma cell percent must be >=10%; new bone lesions/soft tissue plasmacytomas development/existing bone lesions/soft tissue plasmacytomas size increase; hypercalcemia development. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Overall Survival (OS) Time Frame: Randomization up to end of Follow up period (107 months) OS was measured as the time from the date of randomization to the date of death. 2. Percentage of Participants With Any Best Response Category Before PD or Subsequent Therapy Time Frame: Randomization up to EOT (up to 24 months) and thereafter every 4 weeks until initiation of the next line of therapy (up to 107 months) Response was assessed according to IMWG criteria. Best response includes PR, VGPR and CR. PR as per IMWG criteria is 50% reduction of serum M-protein and reduction in 24-hour urinary M-protein >= 90% or = 90% reduction in serum M-protein plus urine M-protein level 50% of waking hours), capable of all self-care, unable to carry out any work activities; 3=capable of only limited self-care, confined to bed/chair >50% of waking hours; 4=completely disabled, cannot carry on any self-care, totally confined to bed/chair; 5=dead. Lower scores indicate improvement. 16. Number of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) or Serious Adverse Events (SAEs) Time Frame: Up to 107 months 17. Number of Participants With Markedly Abnormal Clinical Laboratory Values Reported as TEAEs Time Frame: Up to 107 months 18. Change From Baseline in HRQL Score Based on The EORTC QLQ-C30 Global Quality of Life Domain Time Frame: Baseline up to EOT (up to Month 24) EORTC QLQ-C30 is a cancer-specific instrument that contains 30 items & provides multidimensional assessment of HRQL. EORTC QLQ-C30 includes global health status/quality of life (GHS/QOL), functional scales (physical, role, cognitive, emotional, social), symptom scales (fatigue, pain, nausea/vomiting), and 6 single items (dyspnea, appetite loss, insomnia, constipation, diarrhea, financial difficulties). Most questions from QLQ-C30 are 4-point scale (1/Not at All to 4/Very Much), except Items 29-30, which comprise GHS scale & are 7-point scale (1/Very Poor to 7/Excellent). GHS total scor | — |
Countries
Japan, Refer to "Other" fields
Outcome results
None listed