Relapsed and/or Refractory Non-Hodgkin Lymphoma Study (COMBOSTAT)
|Non-Hodgkin Lymphoma||Drug: Vorinostat in combination with Bortezomib||Phase 2|
|Study Design:||Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase II Study of Combination Vorinostat and Bortezomib in Patients With Relapsed and/or Refractory Non-Hodgkin Lymphoma|
- Determine the response rate of this regimen in this patient population. [ Time Frame: 6 cycles ]
- Determine the progression free survival of this regimen in this patient population. [ Time Frame: entire length of study ]
- Determine the safety and tolerability of this regimen in this patient population. [ Time Frame: throughout course of study ]
- To correlate response rate and progression free survival with pre-treatment and post-treatment NFkB, TRAIL, cyclin D1, histone acetylation, EBV related proteins, and CTA expression. [ Time Frame: 6 cycles ]
|Study Start Date:||June 2010|
|Estimated Primary Completion Date:||April 2014 (Final data collection date for primary outcome measure)|
Experimental: Combination Vorinostat + Bortezomib
Six cycle combination therapy with vorinostat and bortezomib.
Drug: Vorinostat in combination with Bortezomib
Patients will be treated with oral vorinostat on days 1 through 14 followed by a 7-day rest period, for a 21-day treatment cycle for up to 6 cycles in the absence of disease progression or unacceptable toxicity. The patients will receive once-daily oral vorinostat (400 mg) with bortezomib 1.3 mg/m2 as an IV push on days 1, 4, 8, 11.
More selective and less toxic therapeutic strategies are needed to improve cure rates and prolong survival in patients with relapsed and/or refractory non-Hodgkin Lymphoma.
Amongst the multiple new pathways recently studied two have emerged as potentially important targets for new agents in lymphoma. These include the ubiquitin proteasome pathway and the biochemical reactions that control histone acetylation. The first two agents in each class to have been studied in lymphomas are: bortezomib and vorinostat. Bortezomib has been granted FDA approval for the treatment of mantle cell lymphoma and has established activity in a variety of B-cell lymphomas including follicular, marginal zone and diffuse large B-cell lymphoma. Vorinostat or SAHA (suberoylanilide hydroxamic acid) has been FDA approved for the treatment of refractory cutaneous T-cell lymphomas and has also shown activity in other lymphomas.
Synergistic activity between vorinostat and bortezomib has been observed in different cell lines. The proposed study will be a phase II trial of the combination of vorinostat and bortezomib at the recommended dose-schedule in patients with recurrent and/or refractory lymphomas, indolent and aggressive, and B or T.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00837174
|Principal Investigator:||Hector A Preti, M.D.||The Methodist Hospital System|