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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified December 2011 by Copenhagen University Hospital at Herlev.
Recruitment status was  Active, not recruiting
Sponsor:
Information provided by (Responsible Party):
Copenhagen University Hospital at Herlev
ClinicalTrials.gov Identifier:
NCT00866762
First received: March 17, 2009
Last updated: December 9, 2011
Last verified: December 2011
  Purpose

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.


Condition Intervention Phase
Polycythemia Vera
Essential Thrombocythemia
Drug: HDAC inhibitor (MK-0683)
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of MK-0683 in Patients With Polycythaemia Vera and Essential Thrombocythaemia.

Resource links provided by NLM:


Further study details as provided by Copenhagen University Hospital at Herlev:

Primary Outcome Measures:
  • To evaluate the efficacy of study drug (MK-0683) in the treatment of patients with PV and ET. [ Time Frame: one year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To study changes in bone marrow morphology before and after treatment with study drug. [ Time Frame: one year ] [ Designated as safety issue: No ]

Estimated Enrollment: 60
Study Start Date: February 2009
Estimated Study Completion Date: December 2012
Estimated Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Treatment with study drug approximately 6 months and follow-up for 3 months
Drug: HDAC inhibitor (MK-0683)
400 mg once daily for 6 months

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00866762

Locations
Denmark
Copenhagen University Hospital Rigshospitalet
Copenhagen, Denmark, DK-2100
Esberg Hospital
Esbjerg, Denmark, DK-6700
Herlev Hospital
Herlev, Denmark, DK-2730
Odense University Hospital
Odense, Denmark, DK-5000
Roskilde Hospital
Roskilde, Denmark, DK-4000
Regional Hospital Viborg
Viborg, Denmark, DK-8800
Netherlands
VU University Medical Centre
Amsterdam, Netherlands, 1081 HV
Sweden
University Hospital Orebro
Orebro, Sweden, S-70185
Stockholm South General Hospital (Sodersjukhuset)
Stockholm, Sweden, S-11883
Karolinska University Hospital Huddinge
Stockholm, Sweden, S-14186
Sahlgrenska University Hospital & Uddevalla Hospital
Uddevalla, Sweden, S-45180
Uppsala University Hospital
Uppsala, Sweden, S-75185
United Kingdom
Centre for Cancer Research and Cell Biology, Queen's University Belfast
Belfast, Northern Ireland, United Kingdom, BT9 7AB
Cardiff University
Cardiff, United Kingdom, CF14 4XN
Russell's Hall Hospital
Dudley, United Kingdom, DY1 2HQ
St Thomas' Hospital
London, United Kingdom, SE1 7EH
Sponsors and Collaborators
Copenhagen University Hospital at Herlev
Investigators
Principal Investigator: Hans C Hasselbalch, MD Department of Hematology, Copenhagen University Hospital Herlev
  More Information

No publications provided

Responsible Party: Copenhagen University Hospital at Herlev
ClinicalTrials.gov Identifier: NCT00866762     History of Changes
Other Study ID Numbers: MK-0683/092-0
Study First Received: March 17, 2009
Last Updated: December 9, 2011
Health Authority: Denmark: Danish Medicines Agency

Keywords provided by Copenhagen University Hospital at Herlev:
Polycythaemia Vera
Polycythemia Vera
Essential Thrombocythaemia
Essential Thrombocythemia
HDAC-inhibitor
Haematology
Hematology
Haematological disorder
Haematological disease
Hematological disorder
Hematological disease

Additional relevant MeSH terms:
Polycythemia Vera
Polycythemia
Thrombocythemia, Essential
Thrombocytosis
Hematologic Diseases
Myeloproliferative Disorders
Bone Marrow Diseases
Blood Coagulation Disorders
Blood Platelet Disorders
Hemorrhagic Disorders
Histone Deacetylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 20, 2014