Study of the Combination of Panobinostat and Carfilzomib in Patients With Relapsed/Refractory Multiple Myeloma
Relapsed/refractory Multiple Myeloma (MM) is an incurable disorder with a poor prognosis. Carfilzomib is a novel proteasome inhibitor with activity in this setting. Panobinostat is a pan-deacetylase inhibitor which has shown synergistic cytotoxicity in vitro and in vivo with proteasome inhibitors. The combination should enhance the activity of both agents against myeloma cells. In Phase I, the optimal doses of the combination of carfilzomib and panobinostat will be determined. Assuming this combination is feasible, the Phase II portion will proceed using the doses determined in Phase I.
|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: Number of patients with adverse events as a measure of safety and tolerability [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]Phase I will determine the maximum tolerated dose (MTD) of the combination of carfilzomib and panobinostat defined as the highest dose level at which ≤1 of 6 subjects experiences a dose-limiting toxicity (DLT) assessed by NCI CTCAE v4.0.
- Phase II: overall response rate [ Time Frame: 18 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.
- time-to-progression (TTP) [ Time Frame: 24 Months ] [ Designated as safety issue: No ]Restaging assessments for TTP at baseline and every 2 cycles (8 weeks).
- progression-free-survival (PFS) [ Time Frame: 24 Months ] [ Designated as safety issue: No ]Restaging assessments for PFS will be done at baseline and every 2 cycles (8 weeks).
- evaluate overall-survival (OS) [ Time Frame: 24 Months ] [ Designated as safety issue: No ]To evaluate overall-survival (OS) After disease progression is documented, patients will be followed every 3 months for survival assessment.
- evaluate number of participants with serious and non-serious adverse events safety by assessing toxicities [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]Evaluate safety by assessing toxicities
|Study Start Date:||December 2011|
|Estimated Study Completion Date:||August 2016|
|Estimated Primary Completion Date:||February 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)
This is an open-label, non-randomized Phase I/II study of patients with relapsed or refractory multiple myeloma. A maximum of four dose levels were evaluated during the Phase I portion and no dose-limiting toxicities (DLTs) were observed. In Phase II, patients with relapsed/refractory multiple myeloma will receive treatment with the dose level 4 panobinostat and carfilzomib combination. Patients will be reevaluated for response to treatment after each cycle (4 weeks). Patients with objective response or stable disease will continue treatment, with subsequent reevaluations every 4 weeks, until disease progression or unacceptable toxicity occurs.
A parallel Phase I study will occur to evaluate a minimum of 3 patients and a maximum of 6 patients following a standard dose escalation design at additional dose levels of the combination of carfilzomib and panobinostat. If these dose levels are found to be tolerable, then additional patients will be recruited into an expansion cohort which will be open at all sites; a maximum of 36 patients (including those recruited into the parallel Phase I study) will be treated at this dose level. Sites will be notified about the expansion cohort and patients will enter in the dose level confirmed in their enrollment confirmation from SCRI Innovations. Up to 80 eligible patients will be treated in the Phase I/II study.
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|