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

NCT ID: NCT00866762

Last Updated: 2011-12-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-02-28

Study Completion Date

2012-12-31

Brief Summary

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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.

Detailed Description

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Conditions

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Polycythemia Vera Essential Thrombocythemia

Keywords

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Polycythaemia Vera Polycythemia Vera Essential Thrombocythaemia Essential Thrombocythemia HDAC-inhibitor Haematology Hematology Haematological disorder Haematological disease Hematological disorder Hematological disease

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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1

Treatment with study drug approximately 6 months and follow-up for 3 months

Group Type EXPERIMENTAL

HDAC inhibitor (MK-0683)

Intervention Type DRUG

400 mg once daily for 6 months

Interventions

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HDAC inhibitor (MK-0683)

400 mg once daily for 6 months

Intervention Type DRUG

Eligibility Criteria

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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


* 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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Copenhagen University Hospital at Herlev

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Hans C Hasselbalch, MD

Role: PRINCIPAL_INVESTIGATOR

Department of Hematology, Copenhagen University Hospital Herlev

Locations

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Copenhagen University Hospital Rigshospitalet

Copenhagen, , Denmark

Site Status

Esberg Hospital

Esbjerg, , Denmark

Site Status

Herlev Hospital

Herlev, , Denmark

Site Status

Odense University Hospital

Odense, , Denmark

Site Status

Roskilde Hospital

Roskilde, , Denmark

Site Status

Regional Hospital Viborg

Viborg, , Denmark

Site Status

VU University Medical Centre

Amsterdam, , Netherlands

Site Status

University Hospital Orebro

Örebro, , Sweden

Site Status

Stockholm South General Hospital (Sodersjukhuset)

Stockholm, , Sweden

Site Status

Karolinska University Hospital Huddinge

Stockholm, , Sweden

Site Status

Sahlgrenska University Hospital & Uddevalla Hospital

Uddevalla, , Sweden

Site Status

Uppsala University Hospital

Uppsala, , Sweden

Site Status

Centre for Cancer Research and Cell Biology, Queen's University Belfast

Belfast, Northern Ireland, United Kingdom

Site Status

Cardiff University

Cardiff, , United Kingdom

Site Status

Russell's Hall Hospital

Dudley, , United Kingdom

Site Status

St Thomas' Hospital

London, , United Kingdom

Site Status

Countries

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Belgium Denmark Netherlands Sweden United Kingdom

Other Identifiers

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MK-0683/092-0

Identifier Type: -

Identifier Source: org_study_id