A study of best available therapy versus Ruxolitinib in patients with high risk Polycythaemia Vera or Essential Thrombocythaemia who are resistant or intolerant to HydroxyCarbamide (standard therapy)

Phase 1

• Conditions: Polycythaemia veraEssential Thrombocythaemia; MedDRA version: 19.0Level: PTClassification code 10036057Term: Polycythaemia veraSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 19.0Level: PTClassification code 10015493Term: Essential thrombocythaemiaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2011-005279-18-GB
• Lead Sponsor: niversity of Birmingham

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2012-01-04
• Last Update Posted: 3 October 2016

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: Not specified

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 < 2.5 x 10^9/L at any dose of HC (for a period of at least 8 weeks)
- Platelet count >400 x 10^9/L and Hb < 11 g/dl at any dose of HC (for a period of at least 8 weeks)
- Platelet count persistently <100 x 109/L at any dose of HC (for a period of at least 8 weeks)
- Progressive splenomegaly or hepatomegaly i.e. enlargement by more than 5cm or appearance of new splenomegaly or hepatomegaly on HC treatment
- Not achieving the desired reduction of haematocrit or packed cell volume with the addition of HC in patients who do not tolerate frequent venesections after 8 weeks of at least 2 g/day of HC (2.5 g/day in patients with a body weight >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

• 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 <100 x 10^9/L or neutrophil count < 1 x 10^9/L not due to therapy.
• Inadequate liver function as defined by ALT/AST >1.5 x ULN
• Inadequate renal function as defined by GFR < 15 mls/min
• Unable to give informed consent

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified