A Study of the Efficacy of MK-0683 in Patients With Polycythaemia Vera and Essential Thrombocythaemia

Polycythemia Vera Clinical Trial

Official title:

A Phase II Study of MK-0683 in Patients With Polycythaemia Vera and Essential Thrombocythaemia.

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00866762
• Other study ID #: MK-0683/092-0
• Status: Active, not recruiting
• Phase: Phase 2
• First received: March 17, 2009
• Last updated: December 9, 2011
• Start date: February 2009
• Est. completion date: December 2012

Study information

• Verified date: December 2011
• Source: Copenhagen University Hospital at Herlev
• Contact: n/a
• Is FDA regulated: No
• Health authority: Denmark: Danish Medicines Agency
• Study type: Interventional

Clinical Trial Summary

The aim of the present study is to evaluate the efficacy and safety of MK-0683 in the treatment of PV and ET. This agent has most recently been shown to be a potent inhibitor of the autonomous proliferation of haematopoietic cells of PV and ET patients carrying the JAK2 V617F mutation. Accordingly, it may be anticipated that MK-0683 - by decreasing the JAK2 allele burden - may influence clonal myeloproliferation and in vivo granulocyte, platelet and endothelial activation , which are considered to be major determinants of morbidity and mortality ( thrombosis, bleeding, extramedullary haematopoiesis , myelofibrosis ) in these disorders. The effects of MK-0683 at the molecular level will be studied by global/ focused gene expression profiling, epigenome profiling and proteomics.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 60
• Est. completion date: December 2012
• Est. primary completion date: August 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Male or female patient > 18 years of age AND

• A confirmed diagnosis of PV AND

• Biochemical evidence of active disease as defined by:

• a need for phlebotomy within last 3 months

• a leukocyte count > 10 x 10^9/L in the absence of infection or inflammation (normal CRP) and/or (PV/ET)

• a platelet count > 450 x 10^9/L in the absence of infection or inflammation (normal CRP)(PV/ET) OR

• Male or female patient > 18 years of age AND

• A confirmed diagnosis of ET AND

• Biochemical evidence of active disease as defined by *a platelet count > 450 x 10^9/L in the absence of infection or inflammation

Inclusion Criteria for both PV and ET:

• Newly diagnosed or previously treated patient in chronic phase OR

• Advanced phase PV or ET as defined by blasts of > 1 x 10^9/L in the peripheral blood and/or white cell count > 30 x 10^9/L OR

• Resistant or refractory PV or ET as defined by haemoglobin < 10.5 gm/dl with a platelet count > 600 x 10^9/L on current therapy OR

• Cycling platelet counts on therapy OR

• 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)

Exclusion Criteria:

• A platelet count > 1500 x 10^9/L (a need for cytoreduction in platelet count)

• Patients of childbearing potential without a negative pregnancy test prior to initiation of study drug

• Women who are breast feeding

• Males and females not using contraceptives if sexually active.

• EGOC Performance status Score > or = 3

• Serum creatinine more than 2 x's teh ULN

• Total serum bilirubin more than 1.5 x's the ULN

• Serum AST/ALT more than 3 x's the ULN

• Interferon alpha within 1 week of day 1

• Hydroxycarbamide within 1 week of day 1

• Anagrelide within 1 week of day 1

• Valproic acid (as an anticonvulsant) within 28 days of day 1

• Any other investigational drug within 28 days of day 1

• Active HIV, HBV or HCV infection

• 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.

• 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.

• Patient has a known allergy or hypersensitivity to study drug.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Essential Thrombocythemia
• Polycythemia
• Polycythemia Vera
• Thrombocythemia, Essential
• Thrombocytosis

Intervention

Drug:
• HDAC inhibitor (MK-0683)
400 mg once daily for 6 months

Locations

Country	Name	City	State
Denmark	Copenhagen University Hospital Rigshospitalet	Copenhagen
Denmark	Esberg Hospital	Esbjerg
Denmark	Herlev Hospital	Herlev
Denmark	Odense University Hospital	Odense
Denmark	Roskilde Hospital	Roskilde
Denmark	Regional Hospital Viborg	Viborg
Netherlands	VU University Medical Centre	Amsterdam
Sweden	University Hospital Orebro	Orebro
Sweden	Karolinska University Hospital Huddinge	Stockholm
Sweden	Stockholm South General Hospital (Sodersjukhuset)	Stockholm
Sweden	Sahlgrenska University Hospital & Uddevalla Hospital	Uddevalla
Sweden	Uppsala University Hospital	Uppsala
United Kingdom	Centre for Cancer Research and Cell Biology, Queen's University Belfast	Belfast	Northern Ireland
United Kingdom	Cardiff University	Cardiff
United Kingdom	Russell's Hall Hospital	Dudley
United Kingdom	St Thomas' Hospital	London

Sponsors (1)

Lead Sponsor	Collaborator
Copenhagen University Hospital at Herlev

Countries where clinical trial is conducted

Denmark,  Netherlands,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To evaluate the efficacy of study drug (MK-0683) in the treatment of patients with PV and ET.		one year	No
Secondary	To study changes in bone marrow morphology before and after treatment with study drug.		one year	No