patients with polycythaemia vera or essential thrombocythaemia or myelofibrosis MedDRA version: 9.1 Level: LLT Classification code 10036057 Term: Polycythaemia vera MedDRA version: 9.1 Level: LLT Classification code 10015493 Term: Essential thrombocythaemia MedDRA version: 12.1 Level: LLT Classification code 10028537 Term: Myelofibrosis
Conditions
Sponsors
Department of Haematology, Herlev Hospital, University of Copenhagen
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: PV: 11. 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 a) A need for phlebotomy within the last 3 months b) a leukocyte count > 10 x 109/L in the absence of infection or inflammation (normal CRP) and/or (PV/ET) c) a platelet count > 450 x 109/L in the absence of infection or inflammation (normal CRP) (PV/ET). 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 a) a platelet count > 450 x 109/L in the absence of infection or inflammation (normal CRP). PV + 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 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). MF: 1. Male or female patient > 18 years of age and 2. A confirmed diagnosis of primary myelofibrosis, post-polycythaemia vera myelofibrosis or post-essential thrombocythaemia myelofibrosis (12,13,55) and 3. Splenomegaly as assessed clinically or by abdominal ultrasound (patients who have had splenectomy for huge splenomegaly can be included ) 4. Newly diagnosed or previously treated patients in chronic phase or advanced phase MF. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
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. It is recommended that 2 reliable forms of contraception be used simultaneously unless abstinence is the chosen method of contraception. Non-pregnant, non-breast-feeding women may be enrolled if they are considered highly unlikely to conceive. Highly unlikely to conceive is defined as (a) surgically sterilized, or (b) postmenopausal, or (c) not heterosexually active for the duration of the study, or (d) heterosexually active and willing to use 2 birth control methods. The 2 birth control methods can be either 2 barrier methods or a barrier method plus a hormonal method to prevent pregnancy, used throughout the study starting with Visit 1. A woman who is =45 years of age and has not had menses for greater than 2 years will be considered postmenopausal. 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 with the exception of cervical intraepithelial neoplasia, basal cell carcinoma of the skin, or other localized malignancy that has undergone potentially curative therapy with no evidence of that disease for five years, and who is deemed to be at low risk for recurrence by his/her treating physician. 17. Patient has a known allergy or hypersensitivity to vorinostat capsules.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: (1) To evaluate efficacy of vorinostat in the treatment of patients with polycythaemia vera (PV) or essential thrombocythaemia (ET) (2) To evaluate if vorinostat as monotherapy of patients with PV or ET is followed by a decline in clonal myeloproliferation as assessed by conventional disease activity parameters (a decrease in the need of phlebotomy ( PV), leukocyte and platelet count) ;Secondary Objective: (1) To study changes in bone marrow morphology before and after treatment with vorinostat. (2) To investigate whether treatment with vorinostat influences the JAK2 mutation status as assessed by quantitative PCR. (3) To perform integrated gene expression (global and focused) profiling, epigenome profiling and proteome studies (serum-based) before and during treatment with vorinostat in order to describe in detail the various (heterogeneous) response patterns at the molecular level. (4) To study immune cells and function (dendritic cells, regulatory T-cells, NK-cells and specific T-cell responses) before and during treatment with vorinostat. (5) To study in vivo granulocyte, platelet and endothelial activation before and during treatment with vorinostat. (6) To evaluate the safety of vorinostat in the treatment of patients with polycythaemia vera (PV) and essential thrombocythaemia (ET). ;Primary end point(s): | — |
Countries
Denmark, Netherlands, Sweden, United Kingdom
Outcome results
None listed