The purpose of this study for Phase l is to determine the maximum tolerated dose of panobinostat given in combination with carfilzomib, lenalidomide, and dexamethasone in 28-day cycles as induction (initial) therapy to participants with newly diagnosed multiple myeloma. In Phase ll, investigators will evaluate the safety (side effects) and efficacy (effectiveness) of panobinostat in combination with carfilzomib, lenalidomide, and dexamethasone.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Induction Phase: Panobinostat (dose escalation beginning at 10 mg) will be administered 3 times a week (TIW) by mouth every other week starting on day 1 of each cycle. Maintenance Phase: Panobinostat will be administered TIW by mouth every other week starting on day 1 of each cycle. The dose of panobinostat during maintenance phase will be the same dose taken during cyce 8 of induction phase.
Induction Phase: Carfilzomib will be administered at 20 mg/m\^2 on Cycle 1 Day 1. Beginning on Cycle 1 Day 2 the carfilzomib dose will be according to the assigned level of 27 mg/m\^2 or 36 mg/m\^2. Carfilzomib will be administered twice weekly IV on Days 1,2, 8,9,15, and 16.
Induction Phase: Lenalidomide (25 mg) will be administered once-daily by mouth on Days 1-21, 25. Maintenance Phase: Lenalidomide (10 mg) will be administered once-daily by mouth on days 1-21.
Phase I: Maximum Tolerated Dose (MTD)
MTD of the Ca-R-Pa-Diem given in combination to newly diagnosed Multiple Myeloma patients.
Time frame: Up to 8 months
Stringent Complete Remission (sCR) Rate after 4 and 8 Cycles of Treatment
Response rates by International Myeloma Working Group Uniform Response Criteria (IMWG-URC). Complete Response (CR): Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and \< 5% plasma cells in bone marrow. sCR: CR plus normal free light chain (FLC) ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence.
Time frame: Up to 8 months
Phase II: Overall Response Rate (ORR)
Overall response rate will be the proportion of participants who achieved Stringent Complete Response (sCR), Complete Response (CR), Very Good Partial Response (VGPR), or Partial Response (PR). Response rate determined by IMWG-URC will be calculated based on the number of participants with each of response categories (sCR, CR, VGPR, PR, and progressive disease) at each treatment cycle.
Time frame: Up to 36 months
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Induction Phase: Dexamethasone (20 mg) will be administered twice weekly by mouth or by IV on Days 1,2, 8, 9, 15, and 16.