Phase I/II Study of the Combination of Panobinostat and Carfilzomib in Patients with Relapsed/Refractory Multiple Myeloma.
AUTHORS
- PMID: 25710456 [PubMed].
ABSTRACT
ABSTRACT The purpose of this study is to assess the safety and efficacy of the combination of panobinostat and carfilzomib in patients with relapsed/refractory multiple myeloma. Patients with multiple myeloma who had relapsed after at least one prior treatment were eligible to participate. In the dose escalation portion of the study a standard 3+3 design was used to determine the maximum tolerated dose of 4 planned dose levels of the combination of carfilzomib and panobinostat. Panobinostat was administered on Days 1, 3, 5, 15, 17, 19. Carfilzomib was administered Days 1, 2, 8, 9, 15, and 16 of each 28-day cycle. Treatment was continued until progression or intolerable toxicity. Forty-four patients were accrued to the trial, 13 in the Phase I and 31 in the Phase II portion of the study. Median age was 66 years and the median number of prior therapies was 5. The expansion dose was established as 30 mg panobinostat, 20/45 mg/m2 carfilzomib. The overall response rate was 67% for all patients, 67% for patients refractory to prior proteasome inhibitor treatment and 75% for patients refractory to prior immune modulating drug treatment. With a median follow up of 17 months, median progression-free survival was 7.7 months, median time to progression was 7.7 months, and median overall survival has not been reached. The regimen was well tolerated, although there were several panobinostat dose reductions. The combination of panobinostat and carfilzomib is feasible and effective in relapsed/refractory multiple myeloma patients. (Trial registered at ClinicalTrials.gov: NCT01496118).
ABSTRACT The purpose of this study is to assess the safety and efficacy of the combination of panobinostat and carfilzomib in patients with relapsed/refractory multiple myeloma. Patients with multiple myeloma who had relapsed after at least one prior treatment were eligible to participate. In the dose escalation portion of the study a standard 3+3 design was used to determine the maximum tolerated dose of 4 planned dose levels of the combination of carfilzomib and panobinostat. Panobinostat was administered on Days 1, 3, 5, 15, 17, 19. Carfilzomib was administered Days 1, 2, 8, 9, 15, and 16 of each 28-day cycle. Treatment was continued until progression or intolerable toxicity. Forty-four patients were accrued to the trial, 13 in the Phase I and 31 in the Phase II portion of the study. Median age was 66 years and the median number of prior therapies was 5. The expansion dose was established as 30 mg panobinostat, 20/45 mg/m2 carfilzomib. The overall response rate was 67% for all patients, 67% for patients refractory to prior proteasome inhibitor treatment and 75% for patients refractory to prior immune modulating drug treatment. With a median follow up of 17 months, median progression-free survival was 7.7 months, median time to progression was 7.7 months, and median overall survival has not been reached. The regimen was well tolerated, although there were several panobinostat dose reductions. The combination of panobinostat and carfilzomib is feasible and effective in relapsed/refractory multiple myeloma patients. (Trial registered at ClinicalTrials.gov: NCT01496118).
Tags: Alumni Publications 2015