Open-label study to evaluate the safety and efficacy of Ixazomib in combination with Lenalidomide and Dexamethasone in patients with newly diagnosed multiple myeloma (MM). The patient population will consist of adult men and women up to 65 years, who have a confirmed diagnosis of MM who meet eligibility criteria.
Patients will receive induction therapy, comprising three cycles with Ixazomib, plus Lenalidomide and Dexamethasone. Peripheral Blood Stem Cells (PBSC) will be mobilized within 2 weeks (+/- 1 week) after the last dose of Lenalidomide, with Cyclophosphamide plus G-CSF or Granulocyte-CSF(Colony Stimulating Factor). Intensification: High Dose Melphalan (HDM) will be performed within 3 weeks +/- 1 week following stem cell harvest. After Peripheral Blood Stem Cell Transplantation, patient will enter in the consolidation phase: Early consolidation (consolidation part 1) will start 2 months after transplantation and will comprise 2 cycles of MLN - Rd (MLN R identical to induction therapy but low dose of Dexamethasone). Late consolidation (consolidation part 2) will consist in 6 additional cycles of Ixazomib plus Lenalidomide. No Dexamethasone. Maintenance therapy will start within 28 days after the last dose of Lenalidomide in last cycle of Late Consolidation for thirteen 28-day cycles (approximately 12 months duration) Patients will be seen at regular treatment cycle intervals while they are participating in the study. Response will be assessed according to the International Myeloma Working Group (IMWG) criteria until disease progression. All patients will be followed for survival after progression.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
46
induction therapy: comprising three 28-day cycles with 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. Early consolidation : (consolidation part 1) will start 2 months (-/+ 14 days) after transplantation and will comprise 2 cycles of MLN - Rd (MLN R identical to induction therapy but low dose of Dexamethasone 20mg/d once a week). Late consolidation (consolidation part 2) will consist in 6 additional 28-day cycles of Ixazomib (4 mg on Days 1, 8 and 15) plus Lenalidomide (25 mg on Days 1 through 21).
induction therapy: comprising three 28-day cycles with 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. Early consolidation : (consolidation part 1) will start 2 months (-/+ 14 days) after transplantation and will comprise 2 cycles of MLN - Rd (MLN R identical to induction therapy but low dose of Dexamethasone 20mg/d once a week). Late consolidation (consolidation part 2) will consist in 6 additional 28-day cycles of Ixazomib (4 mg on Days 1, 8 and 15) plus Lenalidomide (25 mg on Days 1 through 21). Maintenance therapy will start within 28 days after the last dose of Lenalidomide in last cycle of Late Consolidation: Lenalidomide 10 mg/d taken on Days 1 through 21 for thirteen 28-day cycles
University Hosptial Toulouse
Toulouse, France
rate of stringent complete response
after consolidation and before maintenance therapy
Time frame: 13 months
Adverse events
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time frame: up 60 Months
response rates
response rates according to the IMWG criteria after induction, high dose Melphalan, early consolidation, late consolidation and maintenance therapy
Time frame: 3 months, 5 months, 7 months, 13 months, 25 months
Progression free survival
Time frame: 60 months
overall survival
Time frame: 60 months
Percentage of patients for whom more than 5X106 CD34 cells will be collected.
At stem cell harvest
Time frame: 3 months
Correlation between presence of deletion 17p and response rate
biological prognostic factors assessed at D1 influencing outcome and response rates assessed at 60th month
Time frame: 60 months
Correlation between presence of translocation4-14 and response rate
biological prognostic factors assessed at D1 influencing outcome and response rates assessed at 60th month
Time frame: 60 months
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induction therapy: comprising three 28-day cycles with 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. Early consolidation : (consolidation part 1) will start 2 months (-/+ 14 days) after transplantation and will comprise 2 cycles of MLN - Rd (MLN R identical to induction therapy but low dose of Dexamethasone 20mg/d once a week).