Condition category
Cancer
Date applied
12/04/2012
Date assigned
12/04/2012
Last edited
10/03/2015
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
No longer recruiting

Contact information

Type

Scientific

Primary contact

Mrs Sonia Fox

ORCID ID

Contact details

Edgbaston
Birmingham
B15 2TT
United Kingdom
-
MAJIC@trials.bham.ac.uk

Additional identifiers

EudraCT number

2011-005279-18

ClinicalTrials.gov number

Protocol/serial number

11941

Study information

Scientific title

A randoMised study of best Available therapy versus JAK Inhibition in patients with high risk polycythaemia vera or essential thrombocythaemia who are resistant or intolerant to hydroxyCarbamide

Acronym

MAJIC

Study hypothesis

MAJIC is a phase II, randomised, open-label, two arm, multicentre clinical trial. The trial aims 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.

More information can be found at http://public.ukcrn.org.uk/search/StudyDetail.aspx?StudyID=11941

On 10/03/2015 the overall trial end date was changed from 02/12/2013 to 31/07/2020.

Ethics approval

NRES Committee North West - Liverpool Central, 25/01/2012, ref: 12/NW/0045

Study design

Randomised; Interventional; Design type: Treatment

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Condition

Topic: National Cancer Research Network; Subtopic: Haematological Oncology; Disease: Miscellaneous

Intervention

1. Ruxolitinib, JAK I/II inhibitor
2. Best Available Therapy: This would be the clinicians choice of second line treatment that the patient would receive outside of the trial. This can be any active (non investigational) agent used alone or in combination but not solely venesection or supportive care.

Follow Up Length: 60 month(s)
Study Entry : Single Randomisation only

Intervention type

Drug

Phase

Phase II

Drug names

Ruxolitinib

Primary outcome measures

Complete response rates within 1 year

Secondary outcome measures

1. Partial response rates as defined by European LeukemiaNet criteria within 1 year of treatment
2. Duration of response
3. Toxicity profile of Ruxolitinib based on CTC criteria
4. Dose Intensity
5. Histological response: bone marrow biopsy analysis criteria as defined by European LeukemiaNet
6. Molecular response: JAK2V617F status quantitation; criteria defined by European LeukemiaNet
7. Haemorrhagic and thromboembolic event rate
8. Quality of life and disease symptom burden
9. Overall survival
10. Progression free survival

Overall trial start date

04/06/2012

Overall trial end date

31/07/2020

Reason abandoned

Eligibility

Participant inclusion criteria

Inclusion criteria for PV:
1. Male or female patient >=18 years of age
2. A confirmed diagnosis of high risk PV. High Risk is defined as ANY ONE of the following
2.1. Age >60 years
2.2. Previous documented thrombosis
2.3. 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
2.4. Significant splenomegaly (i.e. > 5cm below costal margin on palpation) or symptomatic (splenic infarcts or requiring analgesia)
2.5. Platelets > 1000 x 10^9/L
2.6. Diabetes or hypertension requiring pharmacological therapy for > 6 months

Inclusion criteria for ET:
1. Male or female patient >=18 years of age
2. A confirmed diagnosis of high risk ET. High risk is defined as ANY ONE of the following:
2.1. Age > 60 years
2.2. Platelet count > 1500 x 10^9/L
2.3. Previous documented thrombosis
2.4. 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
2.5. Previous haemorrhage related to ET Diabetes or hypertension requiring pharmacological therapy for > 6 months
3. ALL patients must also be either intolerant OR resistant to Hydroxycarbamide (HC) based on the following established criteria: Any ONE of the following:
3.1. Platelet count >600 x 10^9/L after 8 weeks of at least 2 g/day or maximum tolerated dose (MTD) of HC (2.5 g/day in patients with a body weight>80 kg)
3.2. 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)
3.3. 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)
3.4. Platelet count persistently <100 x 109/L at any dose of HC (for a period of at least 8 weeks)
3.4. Progressive splenomegaly or hepatomegaly i.e. enlargement by more than 5cm or appearance of new splenomegaly or hepatomegaly on HC treatment
3.5. 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)
3.6. 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)
3.7. Thrombosis or haemorrhage while on therapy
3.8. 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
Target Gender: Male & Female ; Lower Age Limit 18 years

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 290; UK Sample Size: 290

Participant exclusion criteria

1. Pregnant and lactating patients (patients of childbearing potential must have a negative pregnancy test prior to study entry)
2. Patients and partners of childbearing potential not willing to use effective contraception
3. Eastern Cooperative Oncology Group Performance Status Scale (ECOG) Performance Status Score >= 3
4. Current rapid or paroxysmal atrial fibrillation
5. Uncontrolled or unstable angina
6. Recent (6 months) myocardial infarction or acute coronary syndrome or any clinically significant cardiac disease > New York Heart Association (NYHA) Class II
7. Previous treatment with a Janus kinase 2 (JAK2) inhibitor
8. 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
9. Inadequate liver function as defined by aspartate aminotransferase/alanine aminotransferase (ALT/AST) >1.5 x upper limit normal (ULN)
10. Inadequate renal function as defined by Glomerular filtration rate (GFR) < 15 mls/min
11. Unable to give informed consent

Recruitment start date

04/06/2012

Recruitment end date

31/07/2015

Locations

Countries of recruitment

United Kingdom

Trial participating centre

University of Birmingham
Birmingham
B15 2TT
United Kingdom

Sponsor information

Organisation

University of Birmingham (UK)

Sponsor details

Edgbaston
Birmingham
B15 2TT
United Kingdom

Sponsor type

University/education

Website

Funders

Funder type

Charity

Funder name

Leukaemia & Lymphoma Research (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes