Polycythaemia vera Essential Thrombocythaemia MedDRA version: 19.0 Level: PT Classification code 10036057 Term: Polycythaemia vera System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 19.0 Level: PT Classification code 10015493 Term: Essential thrombocythaemia System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Jakavi
Product Name: Jakavi
Pharmaceutical Form: Tablet
INN or Proposed INN: Ruxolitinib
CAS Number: 941678-49-5
Current Sponsor code: RG_11-164
Concentration unit: mg milligram(s)
Concent
Sponsors
University of Birmingham
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion Criteria for PV • Male or female patient = 18 years of age • A confirmed diagnosis of high risk* PV *High Risk is defined as ANY ONE of the following: - Age >60 years - Previous documented thrombosis (including Transient Ischaemic Attack (TIA)), erythromelalgia or migraine (severe, recurrent, requiring medications, and felt to be secondary to the MPN) either after diagnosis or within 10 years before diagnosis and considered to be disease related - Significant splenomegaly (i.e. > 5cm below costal margin on palpation) or symptomatic (splenic infarcts or requiring analgesia) - Platelets > 1000 x 10^9/L - Diabetes or hypertension requiring pharmacological therapy for > 6 months Inclusion criteria for ET • Male or female patient = 18 years of age • A confirmed diagnosis of high risk* ET *High risk is defined as ANY ONE of the following: - Age > 60 years - Platelet count > 1500 x 10^9/L - Previous documented thrombosis (including Transient Ischaemic Attack (TIA)), erythromelalgia or migraine (severe, recurrent, requiring medications, and felt to be secondary to the MPN) either after diagnosis or within 10 years before diagnosis and considered to be disease related - Previous haemorrhage related to ET - Diabetes or hypertension requiring pharmacological therapy for > 6 months ALL patients MUST ALSO be EITHER intolerant OR resistant to Hydroxycarbamide (HC) based on the following established criteria: Any ONE of the following: - Platelet count >600 x 10^9/L after 8 weeks of at least 2 g/day or MTD of HC (2.5 g/day in patients with a body weight>80 kg) - Platelet count >400 x 10^9/L and WBC 400 x 10^9/L and Hb 80 kg) - Not achieving the desired stable reduction of WBC when leukocytes are a target of therapy after 8 weeks of at least 2 g/day or MTD of HC (2.5 g/day in patients with a body weight>80 kg) - Thrombosis or haemorrhage (including Transient Ischaemic Attack (TIA)) while on therapy - Presence of leg ulcers or other unacceptable HC-related non-haematological toxicities, such as unacceptable mucocutaneous manifestations, gastrointestinal symptoms, pneumonitis or fever at any dose of HC. OR Cycling platelet counts on therapy - Disease related symptoms not controlled by hydroxycarbamide The patient can have met any one of the above criteria AT ANY POINT in their disease whilst on Hydroxycarbamide. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 145 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 145
Exclusion criteria
Exclusion criteria: • Pregnant and lactating patients (patients of childbearing potential must have a negative pregnancy test prior to study entry) • Patients and partners of childbearing potential not willing to use effective contraception • ECOG Performance Status Score = 3 • Uncontrolled rapid or paroxysmal atrial fibrillation, uncontrolled or unstable angina, recent (6 months) myocardial infarction or acute coronary syndrome or any clinically significant cardiac disease > NYHA Class II • Patients who have transformed to myelofibrosis • Previous treatment with ruxolitinib • Previous (within the last 12 months) or current platelet count 1.5 x ULN • Inadequate renal function as defined by GFR < 15 mls/min • Unable to give informed consent
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate and evaluate the activity and safety (in terms of complete haematological response within one year) of Ruxolitinib in the treatment of patients with Polycythaemia Vera (PV) or Essential Thrombocythaemia (ET) who have met criteria for resistance or intolerance of hydroxycarbamide (HC) therapy.;Secondary Objective: • Partial response rates as defined by European LeukemiaNet criteria within 1 year of treatment • Duration of response • To determine the toxicity profile of Ruxolitinib based on CTC criteria • Dose intensity • To assess the histological response: bone marrow biopsy analysis criteria as defined by European LeukemiaNet • To assess the molecular response: JAK2 V617F status quantitation; criteria defined by European LeukemiaNet • To assess the haemorrhagic and thromboembolic event rate • To assess change in quality of life and disease symptom burden • Overall survival • Progression free survival;Primary end point(s): Complete Response rates as defined by European LeukemiaNet criteria within 1 year of treatment. ;Timepoint(s) of evaluation of this end point: Once all patients have been on study for 1 year | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Partial response rates as defined by European LeukemiaNet criteria within 1 year of treatment • Duration of response • Toxicity profile of Ruxolitinib based on CTC criteria • Dose Intensity • Histological response: bone marrow biopsy analysis criteria as defined by European LeukemiaNet • Molecular response: JAK2 V617F status quantitation; criteria defined by European LeukemiaNet • Haemorrhagic and thromboembolic event rate • Quality of life and disease symptom burden • Overall survival • Progression free survival ;Timepoint(s) of evaluation of this end point: Once all patients have been on study for 5 years | — |
Countries
United Kingdom
Contacts
Public ContactSonia Fox
University of Birmingham
Outcome results
None listed