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

Sponsor

Copenhagen University Hospital at Herlev (Other)

Overall Status

Unknown status

CT.gov ID

NCT00866762

Collaborator

(none)

Enrollment

Locations

Arm

Duration (Months)

3.8

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

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

Study Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Feb 1, 2009

Anticipated Primary Completion Date :

Aug 1, 2012

Anticipated Study Completion Date :

Dec 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
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

Arm

Intervention/Treatment

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

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

To study changes in bone marrow morphology before and after treatment with study drug. [one year]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	Copenhagen University Hospital Rigshospitalet	Copenhagen		Denmark	DK-2100
2	Esberg Hospital	Esbjerg		Denmark	DK-6700
3	Herlev Hospital	Herlev		Denmark	DK-2730
4	Odense University Hospital	Odense		Denmark	DK-5000
5	Roskilde Hospital	Roskilde		Denmark	DK-4000
6	Regional Hospital Viborg	Viborg		Denmark	DK-8800
7	VU University Medical Centre	Amsterdam		Netherlands	1081 HV
8	University Hospital Orebro	Orebro		Sweden	S-70185
9	Stockholm South General Hospital (Sodersjukhuset)	Stockholm		Sweden	S-11883
10	Karolinska University Hospital Huddinge	Stockholm		Sweden	S-14186
11	Sahlgrenska University Hospital & Uddevalla Hospital	Uddevalla		Sweden	S-45180
12	Uppsala University Hospital	Uppsala		Sweden	S-75185
13	Centre for Cancer Research and Cell Biology, Queen's University Belfast	Belfast	Northern Ireland	United Kingdom	BT9 7AB
14	Cardiff University	Cardiff		United Kingdom	CF14 4XN
15	Russell's Hall Hospital	Dudley		United Kingdom	DY1 2HQ
16	St Thomas' Hospital	London		United Kingdom	SE1 7EH