A Pilot Study of Oral Vorinostat Plus Oral Eltrombopag Support in Patients With Lymphoma (VEIL)
Vorinostat is a drug (Histone Deacetylase Inhibitor [HDACi]) administered orally that has been approved in United States for the patients with cutaneous Tcell lymphoma (CTCL) who have progressive, persistent or recurrent disease on or following two systemic therapies.
In the early period of treatment with vorinostat, some patients may experience low platelet counts. Therefore this study will be examining the combination of these two medications (Vorinostat and eltrombopag) to assess if eltrombopag can overcome the low platelets during treatment with vorinostat.
Eltrombopag is a drug administered orally designed to mimic the protein thrombopoietin, which causes the body to make more platelets. Eltrombopag has been registered in Australia and approved overseas to treat patients with chronic ITP (Immune Thrombocytopenia Purpura) a disease where patients destroy their own platelets very rapidly and thus develop low platelet count) but it is not registered and it is not yet known whether eltrombopag can increase platelet counts in patients treated with the HDACi.
The aim of this project is to test whether Vorinostat and eltrombopag can be safely combined, and to test whether they are effective in participants with T-cell lymphoma involving the skin or patients with relapsed/refractory follicular lymphoma (FL), marginal zone lymphoma (MZL), or mantle cell lymphoma (MCL)
A total of 25 people with Cutaneous T cell lymphoma/ CTCL, marginal zone lymphoma, follicular lymphoma or mantle cell lymphoma will be recruited in this study.
Marginal Zone Lymphoma
Mantle Cell Lymphoma
Drug: Eltrombopag and Vorinostat
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Pilot Study of Oral Vorinostat Plus Oral Eltrombopag Support in Patients With Lymphoma (VEIL)|
- The occurrence of all grade III/IV adverse events (haematological and non haematological) during vorinostat and eltrombopag combination therapy [ Time Frame: One year from trial entry ] [ Designated as safety issue: Yes ]The period of observation for the primary endpoint is defined as the observation for 6 cycles of eligible patients who have commencement eltrombopag following commencement of vorinostat.
- Occurrence of thrombocytopenia (TCP) with vorinostat therapy and response to eltrombopag: platelet, transfusion and bleeding endpoints [ Time Frame: One year from trial entry ] [ Designated as safety issue: No ]
Occurrence & severity of thrombocytopenia (TCP), all grades at baseline & during first 6 vorinostat cycles.
Occurrence & severity of worsening grade of TCP (relative to day 1 cycle 1 of vorinostat therapy) after cycle 1 day 8.
Occurrence & severity of TCP following withdrawal of eltrombopag in patients who had protocol-specified withdrawal of eltrombopag.
Occurrence of platelet response, defined as a cycle nadir platelet count showing a 50% improvement in platelet nadir compared to previous cycle & at least an absolute increase of 20x109/L.
Occurrence of grade III/IV TCP during vorinostat treatment cycle among patients who experience a platelet nadir ≤25 x109/L, receive eltrombopag & who then achieve a platelet response.
Percentage drop in platelet count from day 1 of cycle to nadir & percentage drop in neutrophil count from day 1 of cycle to nadir, for each cycle.
Occurrence & severity of clinically significant bleeding events defined as per the WHO bleeding scale.
|Study Start Date:||October 2012|
|Estimated Study Completion Date:||November 2017|
|Estimated Primary Completion Date:||October 2015 (Final data collection date for primary outcome measure)|
Experimental: Eltrombopag and vorinostat combination therapy
Daily oral intake of 400mg vorinostat if necessary with combination therapy eltrombopag commencing at 50mg per day increasing to a maximum of 200mg per day
Drug: Eltrombopag and Vorinostat
4 week mono-therapy eltrombopag, commencing at 50mg/day, increasing to 200mg. Daily intake of 400mg vorinostat for minimum of 6 cycles, each cycle of 4 weeks, possibly in combination with daily intake eltrombopag commencing at 50mg/day at a maximum dose of 200md/day (150mg/day for subjects of East-Asian ancestry)
Please refer to this study by its ClinicalTrials.gov identifier: NCT01500538
|Peter MacCallum Cancer Centre|
|Melbourne, Victoria, Australia, 3002|
|Principal Investigator:||Michael Dickinson, MBBS (Hons), FRCPA||Peter MacCallum Cancer Centre, Australia|