Panobinostat/Velcade in Multiple Myeloma
Multiple myeloma (MM) accounts for approximately 1% of all malignancies and 10% of hematological tumors, representing the second most frequently occurring hematological malignancy in the United States. At any one time, 50,000 people suffer from MM, and approximately 15,000 are diagnosed each year. The median age is approximately 65 years, although occasionally MM occurs in the second decade of life.
Bortezomib and panobinostat intravenous (IV) are active agents in multiple myeloma and appear to work through different biochemical pathways, suggesting that there may be a synergistic effect using the combination. Both compounds have shown anabolic bone effect, which has been associated to significant anti-myeloma activity.
- To assess the toxicity of bortezomib combined with one of 4 doses of panobinostat IV in patients with relapsed/refractory multiple myeloma, and
- To find the most appropriate doses of bortezomib and panobinostat IV in the combination.
- To assess the effect of bortezomib in combination with panobinostat IV on inducing osteoblast activation in patients with relapsed/refractory myeloma.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I Exploratory Study of Panobinostat IV in Combination With Bortezomib in Relapsed/Refractory Multiple Myeloma Patients|
- To assess the toxicity of bortezomib combined with one of 3 doses of panobinostat IV in patients with relapsed/refractory multiple myeloma, and to find the most appropriate doses of bortezomib and panobinostat IV in the combination. [ Time Frame: June, 2012 ] [ Designated as safety issue: Yes ]
- To assess the effect of bortezomib in combination with panobinostat IV on inducing osteoblast activation in patients with relapsed/refractory myeloma. [ Time Frame: June, 2012 ] [ Designated as safety issue: No ]
|Study Start Date:||April 2009|
|Study Completion Date:||August 2013|
|Primary Completion Date:||August 2013 (Final data collection date for primary outcome measure)|
Experimental: All patients
All participants enrolled.
Drug: Bortezomib (Velcade)
During the study Bortezomib will be administered intravenously as a 3-5 second bolus IV injection, at a dose of 1.0 mg/m2 on days 1, 4, 8, and 11 of each 21-day treatment cycle.
Other Name: VelcadeDrug: Panobinostat
During the study, panobinostat IV will be administered intravenously as once daily on (day 1 and 8 of the 21 day cycle 2 and beyond). Patients enrolled on first group will receive 5 mg/m2 panobinostat IV, second group 10 mg/m2 panobinostat IV, third group 15 mg/m2 panobinostat IV and the fourth group 20 mg/m2 panobinostat IV. Each infusion of panobinostat will be administered over 30 minutes.
The objective of this study is to identify the maximum tolerated dose (MTD) and assess the feasibility and toxicity experience for patients with refractory multiple myeloma treated with bortezomib and one of three doses of panobinostat IV.
This study will accrue up to 18 patients, in 3 groups of up to 6 patients each, depending on experiences of DLT. Patients will be studied as follows, Group 1: Bortezomib 1.0 mg/m2 and panobinostat IV 5 mg/m2 IV, Group 2: Bortezomib 1.0 mg/m2and panobinostat IV 10 mg/m2 IV, Group 3: Bortezomib 1.0 mg/m2 and panobinostat IV 15 mg/m2 IV and Group 4: Bortezomib 1.0 mg/m2 and panobinostat IV 20 mg/m2 IV. Bortezomib will be given on days 1, 4, 8, and 11 during cycle 1 and cycle 2, and panobinostat will be given on days 1 and 8 of the second cycle.
If the MTD is not reached with the first group, the second group will be enrolled and will receive bortezomib1.0 mg/m2 with escalation of panobinostat IV as described above.
Patient's with relapsed/refractory multiple myeloma with at least one line of prior therapy.
Inclusion and exclusion criteria:
Patients must have baseline evaluations performed prior to the first dose of study drug and must meet all inclusion and exclusion criteria. Results of all baseline evaluations, which assure that all inclusion and exclusion criteria have been satisfied, must be reviewed by the principal investigator prior to enrollment of that patient. In addition, the patient must be thoroughly informed about all aspects of the study, including the study visit schedule and required evaluations and all regulatory requirements for informed consent. The written informed consent must be obtained from the patient prior to enrollment. The following criteria apply to all patients enrolled onto the study unless otherwise specified.
|United States, Arkansas|
|Myeloma Institute for Research and Therapy University of Arkansas for Medical Sciences|
|Little Rock, Arkansas, United States, 72205|
|Principal Investigator:||Mauizio Zangari, MD||University of Utah|