A Phase I/II Trial of Romidepsin (Depsipeptide) and Bortezomib in Patients With Relapsed Myeloma
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|ClinicalTrials.gov Identifier: NCT00431990|
Recruitment Status : Unknown
Verified August 2011 by Peter MacCallum Cancer Centre, Australia.
Recruitment status was: Recruiting
First Posted : February 6, 2007
Last Update Posted : August 12, 2011
|Condition or disease||Intervention/treatment||Phase|
|Multiple Myeloma||Drug: depsipeptide Drug: bortezomib Drug: dexamethasone||Phase 1 Phase 2|
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
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||40 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I/II Trial of Romidepsin (Depsipeptide) and Bortezomib in Patients With Relapsed Myeloma|
|Study Start Date :||November 2006|
|Estimated Primary Completion Date :||December 2011|
|Estimated Study Completion Date :||January 2012|
- 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.Other Name: Romidepsin
- 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 cycleOther Name: Velcade
- Drug: dexamethasone
20mg for 2 days with each dose of bortezomib
- Toxicity [ Time Frame: Until progression ]
- Overall response [ Time Frame: Until progression ]
- Time to progression [ Time Frame: Until progression ]
- Overall survival [ Time Frame: Until progression ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00431990
|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|