Study of the Combination of Panobinostat and Carfilzomib in Patients With Relapsed/Refractory Multiple Myeloma
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I/II Study of the Combination of Panobinostat and Carfilzomib in Patients With Relapsed/Refractory Multiple Myeloma|
- Phase 1: Maximum Tolerated Dose (MTD) of panobinostat+carfilzomib [ Time Frame: every 4 weeks, projected 6 months ] [ Designated as safety issue: Yes ]Using a traditional 3+3 dose escalation design, successive cohorts of subjects will receive a fixed dose level of the drug combination. The MTD is defined as the highest dose level at which ≤1 of 6 subjects experiences a dose-limiting toxicity assessed by NCI CTCAE v4.0.
- Phase II: overall response rate [ Time Frame: every 4 weeks, projected 24 months ] [ Designated as safety issue: No ]Defined as the proportion of patients with confirmed complete response, very good partial response, or partial response (CR, VGPR, or PR) according to International Myeloma Working Group Uniform Response Criteria. CR=bone marrow contains ≤5% plasma cells; negative fixation on serum and urine; disappearance of soft tissue plasmacytomas. VGPR=≥90% reduction from baseline serum; urine M-protein level 100mg for 24h. PR=≥50% reduction from baseline in serum M-protein; disappearance of any soft tissue plasmacytomas.
- time-to-progression (TTP) [ Time Frame: At baseline and every 2 cycles (8 weeks), projected 24 months ] [ Designated as safety issue: No ]Measured from date of first protocol treatment until date of first document progression.
- progression-free-survival (PFS) [ Time Frame: At baseline and every 2 cycles (8 weeks), projected 24 months ] [ Designated as safety issue: No ]Measured from date of first protocol treatment until date of tumor progression or death.
- overall-survival (OS) [ Time Frame: Every 8 weeks until progression then every 3 months thereafter, projected 24 months. ] [ Designated as safety issue: No ]Measured from time of first study treatment until date of death or date last known alive.
|Study Start Date:||December 2011|
|Estimated Study Completion Date:||March 2017|
|Primary Completion Date:||December 2016 (Final data collection date for primary outcome measure)|
|Experimental: Carfilzomib and Panobinostat||
Drug: carfilzomib and panobinostat
Cohort 1 (Dose Level 4): Carfilzomib Cycle 1: 20 mg/m2 IV D1, 2 / 45 mg/m2 IV D8, 9, 15, 16; Carfilzomib Cycle 2 to progression: 45 mg/m2 IV D 1, 2, 8, 9, 15, 16;
Panobinostat cycle 1: 30 mg D 1, 3, 5, 15, 17, 19; Panobinostat cycle 2 to progression: 30 mg D 1, 3, 5, 15, 17, 19
Cohort 2 (Dose Level 6): Carfilzomib Cycle 1: 20 mg/m2 IV D1, 2 / 56 mg/m2 IV D8, 9, 15, 16; Carfilzomib Cycle 2: 56 mg/m2 IV D 1, 2, 8, 9, 15, 16;
Panobinostat all cycles: 20 mg D 1, 3, 5, 15, 17, 19.
Other Name: LBH589 (Panobinostat)
In this open-label, non-randomized Phase I/II study, a maximum of 4 planned dose levels of carfilzomib and panobinostat were evaluated to determine the maximum tolerated dose (MTD) to administer. The MTD was not reached so patients in Phase II received treatment at dose level 4 to further assess efficacy. Response to treatment was evaluated after each 4-week cycle. Those having an objective response or stable disease are continuing treatment until disease progression or unacceptable toxicity occurs.
As the MTD in the 4 planned dose levels were not reached, a parallel Phase I study was initiated to examine additional dose levels using a traditional 3+3 design. If these dose levels are tolerable, then more patients will be recruited into an expansion cohort to assess efficacy at the new dose level(s).
Please refer to this study by its ClinicalTrials.gov identifier: NCT01496118
|United States, Colorado|
|Colorado Blood Cancer Institute|
|Denver, Colorado, United States, 80218|
|United States, Florida|
|Florida Cancer Specialists South|
|Fort Myers, Florida, United States, 33916|
|Woodlands Medical Specialists|
|Pensacola, Florida, United States, 32503|
|Florida Cancer Specialists North|
|St. Petersburg, Florida, United States, 33705|
|United States, Indiana|
|Providence Medical Group|
|Terre Haute, Indiana, United States, 47802|
|RHHP/Hope Cancer Center|
|Terre Haute, Indiana, United States, 47802|
|United States, Missouri|
|Research Medical Center|
|Kansas City, Missouri, United States, 64132|
|United States, New Jersey|
|Hematology-Oncology Associates - Northern NJ|
|Morristown, New Jersey, United States, 07962|
|United States, Ohio|
|Oncology Hematology Care, Inc.|
|Cincinnati, Ohio, United States, 45242|
|United States, Oklahoma|
|Cancer Centers of Southwest Oklahoma|
|Lawton, Oklahoma, United States, 73505|
|United States, Tennessee|
|Chattanooga, Tennessee, United States, 37404|
|Nashville, Tennessee, United States, 37205|
|United States, Texas|
|The Center for Cancer and Blood Disorders|
|Fort Worth, Texas, United States, 76104|
|Study Chair:||Jesus Berdeja, MD||SCRI Development Innovations, LLC|