A Study to Evaluate the Efficacy and Safety of Ixazomib in Combination With Lenalidomide and Dexamethasone in Patients With Relapsed and/or Refractory Multiple Myeloma Initially Treated With an Injection of Proteasome Inhibitor-Based Therapy
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|ClinicalTrials.gov Identifier: NCT03416374|
Recruitment Status : Recruiting
First Posted : January 31, 2018
Last Update Posted : March 21, 2019
|Condition or disease||Intervention/treatment||Phase|
|Relapsed and/or Refractory Multiple Myeloma||Drug: Ixazomib Drug: Bortezomib Drug: Carfilzomib Drug: Lenalidomide Drug: Dexamethasone||Phase 4|
The drug being tested in this study is called Ixazomib. Ixazomib is being tested to treat people who have RRMM. This study will look at the effectiveness and safety of IRd in participants with RRMM previously receiving an injectable proteasome inhibitor-based therapy. This study consists of two treatment periods, Treatment Period I and Treatment Period II.
The study will enroll 47 patients. All participants will receive following treatment:
- Combination therapy with Bortezomib + Lenalidomide + Dexamethasone (VRd) or combination therapy with Carfilzomib + Lenalidomide + Dexamethasone (KRd), standard recommended dose according to the package insert of each drug, as Treatment Period I, followed by Combination therapy with Ixazomib 4.0 mg + Lenalidomide 25 mg + Dexamethasone 40 mg (IRd) as Treatment Period II
At start of this study, combination therapy of VRd or KRd will be decided by investigator as Treatment Period I after the baseline evaluations. After the start of Treatment Period I, a participant's eligibility for Treatment Period II is then determined 3 cycles. Participants who meet these eligibility criteria II subsequently continue into Treatment Period II and receive IRd.
This multi-center trial will be conducted in Japan. It is anticipated that the treatment phase of this study will last up to 39 months, including 18 months for enrollment. Participants will make multiple visits to the clinic in treatment period, and follow-up period including a follow-up assessment after last dose of study drug.
|Study Type :||Interventional|
|Estimated Enrollment :||47 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||An Open-label, Single-Arm, Multicenter Study to Evaluate the Efficacy and Safety of Ixazomib in Combination With Lenalidomide and Dexamethasone in Patients With Relapsed and/or Refractory Multiple Myeloma Initially Treated With an Injection of Proteasome Inhibitor-Based Therapy|
|Actual Study Start Date :||March 12, 2018|
|Estimated Primary Completion Date :||August 31, 2020|
|Estimated Study Completion Date :||May 31, 2021|
Experimental: Combination Therapy + Ixazomib Therapy
Bortezomib + Lenalidomide + Dexamethasone, or Carfilzomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)
Carfilzomib intravenous infusions
- Progression-Free Survival (PFS) Rate at 12 Months from the Start of Study Treatment [ Time Frame: Up to 12 months ]PFS rate is defined as the percentage of participants who are alive and have not had disease progression at 12 months after the date of first dose of treatment in Treatment Period I. PFS will be assessed by International Myeloma Working Group (IMWG) Criteria (2014 version). 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.
- Overall Survival (OS) from the Start of Study Treatment [ Time Frame: Up to 39 months as a maximum ]OS is defined as the period from the first dose of treatment in Treatment Period I to the time when death (regardless of the cause of death) is confirmed. Patients who are still alive will be censored at the last confirmed date of survival or the date of data cut-off, whichever is earlier.
- PFS from the Start of Study Treatment [ Time Frame: Up to 39 months as a maximum ]PFS is defined as the period from the first dose of treatment in Treatment Period I to the time of confirmed PD or confirmed death (regardless of the cause of death), whichever is earlier. PFS will be assessed by IMWG Criteria.
- Percentage of Participants who Achieved VGPR or Better (CR + VGPR) [ Time Frame: Up to 39 months as a maximum ]VGPR or better (CR + VGPR) will be assessed by IMWG Criteria. Per IMWG criteria, PR (partial response): ≥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 free light chain (FLC) levels/ ≥50% reduction in bone marrow plasma cells, if ≥30% at baseline/ ≥50% reduction in size of soft tissue plasmacytomas. VGPR (very good PR): serum+urine M-protein detectable by immunofixation but not on electrophoresis/ ≥90% reduction in serum M-protein+urine M-protein level <100 mg/24-hour. CR (complete response): negative immunofixation on serum+urine+disappearance of soft tissue plasmacytomas+<5% plasma cells in bone marrow.
- Rate of Minimal Residual Disease (MRD) in Bone Marrow in Participants who Achieved CR [ Time Frame: Up to 39 months as a maximum ]MRD is defined as the percentage of participants achieving CR who are MRD-negative. If a participant is MRD-positive at their first evaluation and MRD-negative after re-examination, the participant will be considered to be MRD-negative. CR will be assessed by IMWG Criteria.
- Percentage of Participants who Achieve or Maintain Any Best Response [ Time Frame: Up to 39 months as a maximum ]Best response is defined as the cumulative numbers of participants who achieve each level of best response including PR, VGPR and CR assessed with IMWG Criteria, after each cycle of treatment.
- Overall Response Rate (ORR) [ Time Frame: Up to 39 months as a maximum ]ORR is defined as the percentage of participants who achieve a best response of PR or better including stringent complete response (sCR), VGPR and PR assessed with IMWG Criteria, after the start of the study treatment.
- Percentage of Participants Continuing Treatment with Ixazomib at 12 Months from the Start of Study Treatment [ Time Frame: 12 months ]
- Duration of Response (DOR) [ Time Frame: Up to 39 months as a maximum ]DOR is defined as the time from the date of first documentation of response ≥PR to the date of first documentation of PD or death due to any cause. PR and PD will be assessed with IMWG Criteria.
- Patient-Reported Outcome Health-Related Quality of Life (HRQoL) based on European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-C30 (EORTC QLQ-C30) [ Time Frame: Up to 39 months as a maximum ]EORTC QLQ-C30 contains 30 items across 5 functional scales (physical, role, cognitive, emotional, and social), 9 symptom scales (fatigue, nausea and vomiting, pain, dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, and financial difficulties) and a global health status/QOL scale. EORTC QLQ-C30 contains 28 questions (4-point scale where 1=Not at all [best] to 4=Very Much [worst]) and 2 questions (7-point scale where 1=Very poor [worst] to 7= Excellent [best]). Raw scores are converted into scale scores ranging from 0 to 100. For the functional scales and the global health status/QOL scale, higher scores represent better QOL; for the symptom scales, lower scores represent better QOL.
- Patient-Reported Outcome HRQoL based on EORTC Multiple Myeloma Module (EORTC QLQ-MY20) Score [ Time Frame: Up to 39 months as a maximum ]EORTC QLQ-MY20 has 20 items across 4 independent subscales, 2 functional subscales (body image, future perspective), and 2 symptoms scales (disease symptoms, and side effects of treatment). Scores are averaged, and transformed to 0-100 scale. For the future perspective scale, higher score = better perspective of the future. For the body image scale, higher scores = better body image. Higher score for the disease symptoms scale = higher level of symptomatology.
- Evaluation of modified Quality-Adjusted Life-Years (QALYs) [ Time Frame: Up to 39 months as a maximum ]Modified QALYs will be calculated from the score of EORTC QLQ-C30. The health-related quality of life scale score of EORTC QLQ-C30 will be converted into a utility value ranging from 0 to 1, and used to adjust the value of survival years; this value will be assessed as the modified QALY.
- Healthcare Resource Utilization (HCRU) [ Time Frame: Up to 39 months as a maximum ]HCRU will be calculated from Exposure-adjusted rate of hospitalization events (per participants-months) and the duration of hospitalization among participants in Treatment Period I and Treatment Period II.
- Relative Dose Intensity (RDI) [ Time Frame: Up to 39 months as a maximum ]RDI for each study drug 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].
- Percentage of Participants with Bone Lesions (Bone Evaluation) [ Time Frame: Up to 39 months as a maximum ]
- Number of Participants Reporting One or More Treatment-Emergent AEs (TEAEs) [ Time Frame: Up to 39 months as a maximum ]An 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. A TEAE is defined as an adverse event with an onset that occurs after receiving study drug.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03416374
|Contact: Takeda Study Registration Call Centeremail@example.com|
|Study Director:||Study Director||Takeda|