BRITISH SOCIETY FOR HAEMATOLOGY

Study Population:
Patients with PV/ET, newly diagnosed and  previously treated patients in chronic phase as well as patients in advanced phase PV,  patients with resistant or refractory PV or ET, patients with cycling platelet counts on therapy and patients intolerant to other therapies.

Inclusion Criteria for PV:
1.       Male or female patient >18 years of age and
2.       A confirmed diagnosis of PV (see appendix 1) and
3.       Biochemical evidence of active disease as defined by:
EITHER        A need for phlebotomy within the last 3 months
OR                A leukocyte count > 10 x 109/L in the absence of infection or inflammation (normal CRP) and/or (PV/ET)
OR                A platelet count > 450  x 109/L in the absence of infection or inflammation
(normal CRP) (PV/ET).

Inclusion Criteria for ET:
1.       Male or female patient >18 years of age and
2.       A confirmed diagnosis of high-risk ET (see appendix 1) and
3.       Biochemical evidence of active disease as defined by:
4.       a) A  platelet count >450 x 109/L  in the absence of infection or inflammation (normal CRP).

 Inclusion Criteria for both PV and ET:
1.       Newly diagnosed or previously treated  patients in chronic phase OR
2.       Advanced phase PV or ET  as defined by blasts of > 1 x 109/L in the peripheral blood and/or white cell count> 30 x 109/L OR
3.       Resistant or refractory PV or ET as defined by a haemoglobin <10.5 gm/dl with a platelet count >600 x 109/L on current therapy OR
4.       Cycling platelet counts on therapy OR
5.       Intolerant to other therapies defined by patients with PV or ET who have side effects on current therapies preventing continuation (leg ulcers on hydroxycarbamide, unacceptable fatigue etc on interferon).

Study timelines:
Treatment 6 months (visit 1-8) 
Follow up 3 months  (visit 9-11)

 Exclusion Criteria
1.       A  platelet count  >1500 x 109/L (a need for cytoreduction in platelet count)
2.       Patients of childbearing potential without a negative pregnancy test prior to initiation of study drug
3.       Women who are breast feeding
4.       Males and females not using contraceptives if sexually active. Check protocol definition for recommended contraceptives.
5.       ECOG Performance Status Score ≥ 3
6.       Serum creatinine more than 2 x’s the ULN
7.       Total serum bilirubin more than 1.5 x’s the ULN
8.       Serum AST/ALT more than 3 x’s the ULN
9.       Interferon alpha within 1 week of day 1
10.    Hydroxycarbamide within 1 week of day 1
11.    Anagrelide within 1 week of day 1
12.    Valproic acid (as an anticonvulsant) within 28 days of day 1
13.    Any other investigational drug within 28 days of day 1
14.    Active HIV, HBV or HCV infection
15.    Any serious concomitant disease or circumstances that could limit compliance with the study, including but not limited to the following: CTCAE grade 3-4 cardiac general & arrhythmia, or psychiatric or social conditions that may interfere with patient compliance
16.    Any prior malignancy
17.    Patient has a known allergy or hypersensitivity to vorinostat capsules