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

NCT00866762 | Unknown Phase 2 DMC

• 1 other identifier: MK-0683/092-0
• Study Type: interventional
• Target: 60
• Locations: 4 countries
• Sites: 16

Brief 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.

Conditions

Polycythemia Vera; Essential Thrombocythemia

Keywords

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

Outcome Measures

Primary Outcomes (1)

• To evaluate the efficacy of study drug (MK-0683) in the treatment of patients with PV and ET.

  one year

Secondary Outcomes (1)

• To study changes in bone marrow morphology before and after treatment with study drug.

  one year

Study Arms (1)

1

EXPERIMENTAL

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

Drug: HDAC inhibitor (MK-0683)

Interventions

HDAC inhibitor (MK-0683) DRUG

400 mg once daily for 6 months

1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• Copenhagen University Hospital at Herlev: lead

Study Sites (16)

Copenhagen University Hospital Rigshospitalet

Copenhagen, DK-2100, Denmark

Location

Esberg Hospital

Esbjerg, DK-6700, Denmark

Location

Herlev Hospital

Herlev, DK-2730, Denmark

Location

Odense University Hospital

Odense, DK-5000, Denmark

Location

Roskilde Hospital

Roskilde, DK-4000, Denmark

Location

Regional Hospital Viborg

Viborg, DK-8800, Denmark

Location

VU University Medical Centre

Amsterdam, 1081 HV, Netherlands

Location

University Hospital Orebro

Örebro, S-70185, Sweden

Location

Stockholm South General Hospital (Sodersjukhuset)

Stockholm, S-11883, Sweden

Location

Karolinska University Hospital Huddinge

Stockholm, S-14186, Sweden

Location

Sahlgrenska University Hospital & Uddevalla Hospital

Uddevalla, S-45180, Sweden

Location

Uppsala University Hospital

Uppsala, S-75185, Sweden

Location

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

Belfast, Northern Ireland, BT9 7AB, United Kingdom

Location

Cardiff University

Cardiff, CF14 4XN, United Kingdom

Location

Russell's Hall Hospital

Dudley, DY1 2HQ, United Kingdom

Location

St Thomas' Hospital

London, SE1 7EH, United Kingdom

Location

MeSH Terms

Conditions

Polycythemia Vera; Thrombocythemia, Essential; Polycythemia; Hematologic Diseases

Interventions

Histone Deacetylase Inhibitors; Vorinostat

Condition Hierarchy (Ancestors)

Bone Marrow Neoplasms; Hematologic Neoplasms; Neoplasms by Site; Neoplasms; Bone Marrow Diseases; Hemic and Lymphatic Diseases; Myeloproliferative Disorders; Blood Coagulation Disorders; Thrombocytosis; Blood Platelet Disorders; Hemorrhagic Disorders

Intervention Hierarchy (Ancestors)

Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids

Study Officials

• Hans C Hasselbalch, MD

  Department of Hematology, Copenhagen University Hospital Herlev

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 17, 2009
• First Posted: March 20, 2009
• Study Start: February 1, 2009
• Primary Completion: August 1, 2012
• Study Completion: December 1, 2012
• Last Updated: December 12, 2011

Record last verified: 2011-12

Locations

DK (6); NL (1); GB (4); SE (5)