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
Overview
- Phase
- Phase 4
- Intervention
- Ixazomib
- Conditions
- Relapsed and/or Refractory Multiple Myeloma
- Sponsor
- Takeda
- Enrollment
- 45
- Locations
- 23
- Primary Endpoint
- Progression-Free Survival (PFS) Rate at 12 Months From the Start of Study Treatment
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
The purpose of this study is to investigate the efficacy and safety of long-term administration of the oral proteasome inhibitor ixazomib as part of ixazomib in combination with lenalidomide and dexamethasone (IRd) therapy in patients with relapsed and/or refractory multiple myeloma (RRMM) treated initially with an injectable proteasome inhibitor-based therapy.
Detailed Description
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Eligibility for Treatment Period I
- •Men and women of age 20 years or older at the time of enrollment.
- •Participants with RRMM.
- •Participants who are planned to start combination therapy with bortezomib, lenalidomide, and dexamethasone (VRd) or carfilzomib, lenalidomide, and dexamethasone (KRd) as second, third or fourth line of treatment.
- •Participants with measurable disease defined by one or more of the following three measurements.
- •Serum M-protein: ≥0.5 gram (g)/ deciliter (dL) (≥ 5 g/ liter \[L\])
- •Urine M-protein: ≥ 200 milligram (mg)/24 hours
- •Serum free light chain assay: involved free light chain concentration ≥ 10 mg/dL (≥ 100 mg/L) provided that the serum free light chain ratio is abnormal
- •Participants with Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2; however, participants with ECOG PS 3 are eligible if they only have symptoms associated with bone lesions.
- •Participants who are considered by the principal investigator or investigator not to be eligible for transplant; or, if considered eligible for transplant, participants who are planned not to undergo transplant for at least 12 months after the start of the study treatment.
Exclusion Criteria
- •Eligibility for Treatment Period I
- •Women who are nursing or pregnant.
- •Participants with another active malignancy, i.e. synchronous active malignancy or previous malignancy with a disease-free period of less than 5 years, except for participants with carcinoma in situ (intraepithelial carcinoma) or intramucosal carcinoma judged to be cured by topical treatment.
- •Participants with poorly controlled active thrombosis.
- •Participants who have participated in a clinical trial of ixazomib or have been treated with ixazomib.
- •Participants who were refractory to either treatment regimen based on lenalidomide and/or proteasome inhibitor(s).
- •Note: Refractory MM is defined as PD on therapy or PD within 60 days after the last dose of a given therapy. Participants who have disease progressed 60 days after the last dose of a given therapy will be considered as relapsed in this study.
- •Participants with ongoing or active systemic infection, known hepatitis B virus infection, known hepatitis C virus infection, or known positivity to human immunodeficiency virus (HIV).
- •Participants who underwent major surgery within 14 days prior to enrollment to Treatment Period I. Surgery for bone lesions is not considered as major surgery.
- •Participants who received radiation therapy within 14 days prior to enrollment to Treatment Period I. If the radiation field is small, 7 days is considered as a sufficient interval between radiation therapy and chemotherapy.
Arms & Interventions
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)
Intervention: Ixazomib
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)
Intervention: Bortezomib
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)
Intervention: Carfilzomib
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)
Intervention: Lenalidomide
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)
Intervention: Dexamethasone
Outcomes
Primary Outcomes
Progression-Free Survival (PFS) Rate at 12 Months From the Start of Study Treatment
Time Frame: Up to 12 months
PFS rate was defined as the percentage of participants who were alive and have not had disease progression at 12 months after the date of first dose of treatment in Treatment Period I. PFS was assessed by International Myeloma Working Group (IMWG) Criteria (2014 version). Per IMWG criteria, progressive disease (PD): serum M-component increase ≥0.5 g/dl or urine M-component increase ≥200 mg/24-hour/ difference between involved and uninvolved free light chain (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.
Secondary Outcomes
- Overall Survival (OS) From the Start of Study Treatment(Up to 39 months as a maximum)
- PFS From the Start of Study Treatment(Up to 39 months as a maximum)
- Percentage of Participants Who Achieved VGPR or Better (CR + VGPR)(Up to 39 months as a maximum)
- Time to Next Treatment (TTNT)(Up to 39 months as a maximum)
- Duration of Therapy (DOT)(Up to 39 months as a maximum)
- Patient-Reported Outcome Health-Related Quality of Life (HRQoL) Based on Global Health Status Scale of European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-C30 (EORTC QLQ-C30)(Baseline and End of Treatment (Up to 23 cycles for VRd Group, Up to 32 cycles for KRd and Overall Group, each cycle was of 28 days))
- Patient-Reported Outcome HRQoL Based on EORTC Multiple Myeloma Module (EORTC QLQ-MY20) Score(Baseline and End of Treatment (Up to 23 cycles for VRd Group, Up to 32 cycles for KRd and Overall Group, each cycle was of 28 days))
- Evaluation of Modified Quality-Adjusted Life-Years (QALYs)(Up to 39 months as a maximum)
- Number of Participants With Minimal Residual Disease (MRD) Positive or Negative in Bone Marrow in Participants Who Achieved CR(Up to 39 months as a maximum)
- Overall Response Rate (ORR)(Up to 39 months as a maximum)
- Percentage of Participants Who Achieve or Maintain Any Best Response(Up to 39 months as a maximum)
- Percentage of Participants Continuing Treatment With Ixazomib at 12 Months From the Start of Study Treatment(12 months)
- Duration of Response (DOR)(Up to 39 months as a maximum)
- Healthcare Resource Utilization (HCRU): Number of Events With Hospitalization Per Participants-Month(Up to 39 months as a maximum)
- Healthcare Resource Utilization (HCRU): Duration of Hospital Stay Per Participants(Up to 39 months as a maximum)
- Relative Dose Intensity (RDI)(Up to 39 months as a maximum)
- Percentage of Participants With Bone Lesions (Bone Evaluation)(Up to 39 months as a maximum)
- Number of Participants Reporting One or More Treatment-Emergent AEs (TEAEs)(Up to 39 months as a maximum)