The main aim is to show that long-term use of ixazomib can improve symptoms of multiple myeloma and provide an effective long-term alternative treatment. Participants will take ixazomib orally (by mouth) with pomalidomide and dexamethasone or lenalidomide and dexamethasone in 28-day treatment cycles. Participants will be treated for a maximum of 39 cycles but may continue to receive ixazomib beyond 39 cycles if they are benefiting from it. A follow-up study visit will occur 30 days after the last dose of ixazomib. Participants will be monitored for up to 3 years.
The main objective is to determine whether an in-class transition (iCT) from a parenteral proteasome inhibitor (PI) regimen to an all-oral ixazomib(NINLARO) regimen can improve outcomes and provide an effective long-term alternative treatment for participants with relapsed and/or refractory multiple myeloma. The drug being tested in this study is called ixazomib (NINLARO). Ixazomib is being tested to treat people who have relapsed and/or refractory multiple myeloma (R/R MM). This study will look at the efficacy and safety of ixazomib in participants with R/R MM who were previously receiving parenteral proteasome inhibitor (PI)-based therapy in combination with pomalidomide or with lenalidomide, and who undergo in-class transition to an oral ixazomib-based combination containing either pomalidomide (cohort A) or lenalidomide (cohort B). The study will enroll approximately 140 patients. Participants will be enrolled to one of the two treatment groups, depending on whether they are transitioning from a pomalidomide- or lenalidomide- based regimen: * Cohort A: Ixazomib 4 mg + Pomalidomide 4 mg + Dexamethasone 40 mg * Cohort B: Ixazomib 4 mg + Lenalidomide 25 mg + Dexamethasone 40 mg Participants who are \>75 years of age at time of enrollment will be instructed to take 20 mg dexamethasone. For participants with moderate or severe hepatic impairment, severe renal impairment, or end-stage renal disease requiring dialysis, the recommended starting dose of ixazomib is 3 mg which can be further reduced to 2.3 mg at investigator's discretion. This multi-center trial will be conducted at approximately 30 study centers across the United States. The overall duration of this study is approximately 5 years or until all participants have died, have been lost to follow-up, or completion of the study by the sponsor, whichever occurs first.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Ixazomib capsules
Pomalidomide capsules
Lenalidomide capsules
Progression Free Survival (PFS)
PFS is defined as the time from the date of the first administration of the study drug regimen ixazomib with pomalidomide and dexamethasone or ixazomib with lenalidomide and dexamethasone (IPd/IRd) to the date of the first documentation of disease progression before the start of next line of therapy based on local laboratory results and the investigator's assessment using modified International Myeloma Working Group (IMWG) response criteria or death due to any cause, whichever occurs first.
Time frame: Up to approximately 5 years
Percentage of Participants Maintaining or Achieving PR, Very Good Partial Response (VGPR), or Complete Response (CR)
Percentage of participants with PR, VGPR, and CR will be determined based on local laboratory results and investigator's assessment using modified IMWG response criteria. CR: No immunofixation on serum/urine, disappearance of soft tissue plasmacytomas, \<5% plasma cells in bone marrow. Participants with measurable disease only by serum free light chain (SFLC) level, normal FLC ratio of 0.26 to 1.65 in addition to CR criteria required. VGPR: Serum/urine M-protein detectable by immunofixation but not on electrophoresis or ≥90% decrease in serum M-protein with urine M-protein \<100 milligram per 24 hours (mg/24 hrs). If disease measurable only by SFLC, ≥90% decrease in difference between involved and uninvolved free light chain (dFLC) levels in addition to VGPR criteria required. PR: ≥50% reduction of serum M-protein and ≥90% reduction in urine M-protein or to \<200 mg/24 hrs, or a ≥50% decrease in dFLC. If present at Baseline, ≥50% reduction in size of soft tissue plasmacytomas required.
Time frame: Up to approximately 5 years
Time to Progression (TTP)
TTP is defined as the time from the date of the first administration of the study drug regimen (IPd/IRd) to the date of the first documentation of disease progression based on local laboratory results and the investigator's assessment using modified IMWG response criteria.
Time frame: Up to approximately 5 years
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Dexamethasone tablets
Duration of Therapy (DoT 1)
DoT 1 is defined as the date of the first administration of the parenteral PI-based regimen to the date of the last administration of any of the three drugs in the study drug regimen.
Time frame: Up to approximately 5 years
Duration of Therapy (DoT 2)
DoT 2 is defined as the time from the date of the first administration of the study drug regimen (IPd or IRd) to the date of the last administration of any of the three drugs in the study drug regimen.
Time frame: Up to approximately 5 years
Duration of PI Therapy
Duration of parenteral PI therapy is defined as the time from the date of the first administration of the parenteral PI therapy of the regimen preceding the study drug regimen (IPd or IRd) to the date of the last administration of ixazomib therapy
Time frame: Up to approximately 5 years
Duration of Ixazomib Therapy
Duration of ixazomib therapy is defined as the time from the date of the first administration of ixazomib to the date of the last administration of ixazomib therapy.
Time frame: Up to approximately 5 years
Relative Dose Intensity (RDI) for Each Drug in the Treatment Regimen
RDI for each drug in the study drug regimen (IPd/IRd) is defined as 100 × (Total amount of dose taken)/(Total prescribed dose of treated cycles), where total prescribed dose equals (dose prescribed at enrollment) × number of prescribed doses per cycle × the number of treated cycles.
Time frame: Up to approximately 5 years
Percentage of Participants who Experience at Least One Treatment Emergent Adverse Event (TEAE)
An adverse event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (e.g., a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.
Time frame: Up to approximately 5 years