A Phase I/II Trial of Romidepsin (Depsipeptide) and Bortezomib in Patients With Relapsed Myeloma
The purpose of the first phase of the study is to determine whether, and at what dose, depsipeptide, bortezomib and dexamethasone can be safely administered to patients with Multiple Myeloma. The second phase of the study will establish whether depsipeptide, bortezomib and dexamethasone is effective in the treatment of patients with multiple myeloma. The study will also examine the role of maintenance therapy with depsipeptide.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I/II Trial of Romidepsin (Depsipeptide) and Bortezomib in Patients With Relapsed Myeloma|
- Toxicity [ Time Frame: Until progression ] [ Designated as safety issue: Yes ]
- Overall response [ Time Frame: Until progression ] [ Designated as safety issue: No ]
- Time to progression [ Time Frame: Until progression ] [ Designated as safety issue: No ]
- Overall survival [ Time Frame: Until progression ] [ Designated as safety issue: No ]
|Study Start Date:||November 2006|
|Estimated Study Completion Date:||January 2012|
|Estimated Primary Completion Date:||December 2011 (Final data collection date for primary outcome measure)|
Several groups have explored the possible synergistic interactions between proteasome and HDAC inhibitors in malignant hematopoietic cells. Bortezomib and HDACIs synergistically induce apoptosis, mitochondrial injury (via BAX), ROS generation and oxidative injury in human leukemia and myeloma cells.
In view of this evidence, we are proposing a trial to examine the clinical effects of combined romidepsin and bortezomib in patients with relapsed/refractory MM. However, there are currently no data as to whether these drugs are safe to administer in combination or at what dose toxicity they may become unacceptable.
Trial Design Open label, single centre, single arm, phase I/II dose escalation trial of bortezomib-dexamethasone with the addition of romidepsin followed by maintenance therapy until disease progression.
• To determine the maximum tolerated dose (MTD) of romidepsin administered with Bortezomib in patients with relapsed multiple myeloma by the assessment of adverse events and abnormal laboratory values.
• Toxicity evaluation at each of four dose levels presented in the dose-escalation schedule
• To determine the efficacy of this combination at the MTD in terms of (i) overall response, (ii) time to progression and (iii) overall survival
- Overall response (OR), defined as the best response on treatment based on M Protein response criteria with CR documented to EMBT standard and in conjunction with soft tissue plasmacytomas response criteria and corrected serum calcium level.
- Time to progression (TTP), defined as the time from commencement of treatment to the date of first evidence of progressive disease.
- Overall survival (OS), defined as the time from commencement of treatment to the date of death from any cause
|Contact: Joanne Dean||613 9656 1111 ext 1809||Joanne.Dean@petermac.org|
|Contact: Sam Ruell||613 9656 1111 ext 1698||Sam.Ruell@petermac.org|
|Peter MacCallum Cancer Centre||Recruiting|
|Melbourne, Victoria, Australia, 8006|
|Sub-Investigator: Alvin Milner|
|Principal Investigator:||Simon J Harrison, MBBS, PhD.||Peter MacCallum Cancer Centre, Australia|
|Principal Investigator:||Miles Prince, MD||Peter MacCallum Cancer Centre, Australia|