NCT00431990

A Phase I/II Trial of Romidepsin (Depsipeptide) and Bortezomib in Patients With Relapsed Myeloma

• Status: Unknown
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 40 (estimated)
• Sponsor: Peter MacCallum Cancer Centre, Australia · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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. Primary objective: • 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. Primary endpoint: • Toxicity evaluation at each of four dose levels presented in the dose-escalation schedule Secondary objective: • To determine the efficacy of this combination at the MTD in terms of (i) overall response, (ii) time to progression and (iii) overall survival Secondary endpoints: * 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

Conditions

• Multiple Myeloma

Interventions

Type	Name	Description
DRUG	depsipeptide	Cohort 1. Dose escalation, IV, Weeklyx3 in a 4week cycle. Cohort 2A. 12mg/m2, IV, Weeklyx3 in a 4week cycle. Cohort 2B. 12mg/m2, IV, Weeklyx2 in a 3week cycle.
DRUG	bortezomib	Cohort 1 and 2A. 3.5mg/m2, IV, day 1, 4, 8, 11 in 28 day cycle. Cohort 2B. 3.5mg/m2, IV, day 1, 4, 8, 11 in 21 day cycle
DRUG	dexamethasone	20mg for 2 days with each dose of bortezomib

Timeline

• Start date: 2006-11-01
• Primary completion: 2011-12-01
• Completion: 2012-01-01
• First posted: 2007-02-06
• Last updated: 2011-08-12

Locations

1 site across 1 country: Australia