The purpose of this study is to evaluate the efficacy and safety of ixazomib plus lenalidomide and dexamethasone in Japanese participants with relapsed and/or refractory multiple myeloma (RRMM).
This is a phase 2, open label, single arm, multicenter study to evaluate the efficacy and safety of ixazomib plus lenalidomide and dexamethasone in Japanese participants with relapsed and/or refractory multiple myeloma (MM). The participants population will consist of adult men and women who have a confirmed diagnosis of MM, who have received 1 to 3 prior lines of therapy, and who meet other outlined eligibility criteria. Participants will receive study drug (ixazomib 4.mg) on Days 1, 8, and 15 plus lenalidomide (25 mg) on Days 1 through 21 and dexamethasone (40 mg) on Days 1, 8, 15, and 22 of a 28-day cycle. Participants may continue to receive treatment until progressive disease (PD) or unacceptable toxicity, whichever comes first. Dose modifications may be made based on toxicities. Participant with a low creatinine clearance \< 60 mL/min will receive a reduced lenalidomide dose of 10 mg once daily on Days 1 through 21 of a 28-day cycle. The lenalidomide dose may be escalated to 15 mg once daily after 2 cycles if the participant is not responding to treatment and is tolerating the treatment. If renal function normalizes (ie, creatinine clearance \>= 60 mL/min) and the participant continues to tolerate this treatment, lenalidomide may then be escalated to 25 mg once daily. Treatment periods will be defined as 28-day cycles. Participant will be seen at regular treatment cycle intervals while they are participating in the study: four times a treatment cycle for the first 2 cycles, twice a treatment cycle for the 3rd cycle, and then once a treatment cycle for the remainder of their participation in the active treatment and, if applicable, the progression free survival (PFS) and overall survival (OS) follow-up phases of the study. Response will be assessed by investigator according to the International Myeloma Working Group criteria for all participants every 4 weeks until PD. Central laboratory data will be used for serum M-protein, urine M-protein and serum free light chain. All participants will be followed for survival after progression. Participants will be contacted every 12 weeks until death or termination of the study by the sponsor. The study will be closed at 24 months from the enrollment of the last participant.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
34
Ixazomib capsules
Lenalidomide capsules
Dexamethasone Tablets
Unnamed facility
Nagoya, Aichi-ken, Japan
Unnamed facility
Narita, Chiba, Japan
Unnamed facility
Shibukawa, Gunma, Japan
Percentage of Participants With Very Good Partial Response (VGPR) or Better Response (Complete Response (CR) + VGPR)
Response was assessed using International Myeloma Working Group (IMWG) Criteria. CR was defined as negative immunofixation in serum and urine and disappearance of any soft tissue plasmacytomas and \< 5% plasma cells in bone marrow. VGPR was defined as serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level \< 100 mg per 24 hours.
Time frame: Up to approximately 33 months
Progression-free Survival (PFS)
PFS was defined as the time in months from the date of first study drug administration to the date of first documentation of PD or death from any cause, whichever occurred first. PD required one of the following: increase of ≥ 25% from nadir in: serum M-component (absolute increase ≥ 0.5 g/dl); urine M-component (absolute increase ≥ 200 mg/24 hours); in participants without measurable serum and urine M-protein levels the difference between involved and uninvolved free light chain (FLC) levels (absolute increase \> 10 mg/dl); development of new or increase in the size of existing bone lesions or soft tissue plasmacytomas; development of hypercalcemia (corrected serum calcium \> 11.5 mg/dl) attributed solely to plasma cell proliferative disease.
Time frame: Up to approximately 33 months
Overall Response Rate (ORR)
ORR:percentage of participants with CR including stringent complete response(sCR),VGPR,partial response(PR) per independent review committee(IRC)by IMWG criteria.CR: serum,urine -ve immunofixation; disappearance of soft tissue plasmacytomas,\<5%plasma cells in bone marrow(CR in those with only measurable disease by serum FLC levels=normal FLC ratio 0.26 to 1.65+CR criteria).sCR:CR+normal FLC ratio,absence of clonal plasma cells(immunohistochemistry)or 2-to 4-color flow cytometry.VGPR:serum,urine M-protein detectable by immunofixation,not by electrophoresis or ≥90%reduction,\<100mg/24hrs(VGPR in those with only measurable disease by serum FLC levels,requires\>90%decrease in involved-uninvolved FLC level difference).PR: ≥50%reduction of serum M protein+reduction in 24-hr urinary M protein by≥90%/ to\<200mg/24-hr or ≥50%decrease in difference between involved-uninvolved FLC levels/≥50%reduction in bone marrow plasma cells,if≥30%at baseline/≥50%soft tissue plasmacytoma size reduction.
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Unnamed facility
Fukuyama, Hiroshima, Japan
Unnamed facility
Kobe, Hyōgo, Japan
Unnamed facility
Ibaraki, Ibaragi, Japan
Unnamed facility
Sagamihara, Kanagawa, Japan
Unnamed facility
Sendai, Miyagi, Japan
Unnamed facility
Ikoma, Nara, Japan
Unnamed facility
Sunto-gun, Shizuoka, Japan
...and 11 more locations
Time frame: Up to approximately 33 months
Duration of Response (DOR)
DOR was measured as time in months from date of first documentation of response, VGPR or better, and ORR (CR+PR (including sCR and VGPR) or better, to date of first documented PD among participants who responded to treatment. Response was assessed by investigator using IMWG Criteria. CR:negative immunofixation in serum and urine and; disappearance of any soft tissue plasmacytomas and;\<5% plasma cells in bone marrow. sCR:CR plus normal FLC ratio, absence of clonal plasma cells by immunohistochemistry or 2- to 4-color flow cytometry. VGPR:serum and urine M-protein detectable by immunofixation but not on electrophoresis/≥90% reduction in serum M-protein plus urine M-protein level \<100 mg/24 hours. PR:≥50% reduction of serum M protein+reduction in 24-hour urinary M protein by ≥90%/ to \<200 mg/24-hour or ≥50% decrease in difference between involved and uninvolved FLC levels/≥50% reduction in bone marrow plasma cells, if ≥30% at baseline/≥50% reduction in size of soft tissue plasmacytomas.
Time frame: Up to approximately 33 months
Time to Progression (TTP)
TTP was measured as the time in months from the first dose of study treatment to the date of the first documented PD as assessed using IMWG criteria. PD required one of the following: increase of ≥ 25% from nadir in: serum M-component (absolute increase ≥ 0.5 g/dL); urine M-component (absolute increase ≥ 200 mg/24 hours); in participants without measurable serum and urine M-protein levels the difference between involved and uninvolved FLC levels (absolute increase \> 10 mg/dL); development of new or increase in the size of existing bone lesions or soft tissue plasmacytomas; development of hypercalcemia (corrected serum calcium \> 11.5 mg/dL) attributed solely to plasma cell proliferative disease.
Time frame: Up to approximately 33 months
Number of Participants With One or More Treatment-emergent Adverse Events (TEAEs)
An adverse event (AE) is any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not it was related to the medicinal product. A TEAE is defined as any AE that occurred after administration of the first dose of any study drug through 30 days after the last dose of any study drug.
Time frame: Up to approximately 33 months
Number of Participants With NCI CTCAE Grade 3 or Higher TEAEs Related Laboratory Parameters
Laboratory parameters included chemistry and hematology. An AE is any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not it was related to the medicinal product. A TEAE is defined as any AE that occurred after administration of the first dose of any study drug through 30 days after the last dose of any study drug. An AE was graded as per NCI CTCAE.
Time frame: Up to approximately 33 months
Number of Participants With NCI CTCAE Grade 3 or Higher TEAEs Related to Vital Signs
Vital signs included temperature, blood pressure, heart rate, and respiratory rate. An AE is any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not it was related to the medicinal product. A TEAE is defined as any AE that occurred after administration of the first dose of any study drug through 30 days after the last dose of any study drug. An AE was graded as per NCI CTCAE.
Time frame: Up to approximately 33 months
Overall Survival (OS)
OS was defined as the time from the date of first study drug administration to the date of death.
Time frame: Up to approximately 33 months