Contact information
Type
Scientific
Contact name
Mrs Sonia Fox
ORCID ID
Contact details
Edgbaston
Birmingham
B15 2TT
United Kingdom
-
MAJIC@trials.bham.ac.uk
Additional identifiers
EudraCT/CTIS number
2011-005279-18
IRAS number
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(s)
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
Study setting(s)
Hospital
Study 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
Pharmaceutical study type(s)
Phase
Phase II
Drug/device/biological/vaccine name(s)
Ruxolitinib
Primary outcome measure
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 study start date
04/06/2012
Overall study end date
28/03/2022
Reason abandoned (if study stopped)
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(s)
Patient
Age group
Adult
Lower age limit
18 Years
Sex
Both
Target number of participants
Planned Sample Size: 290; UK Sample Size: 290
Total final enrolment
306
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
England, United Kingdom
Study participating centre
University of Birmingham
Birmingham
B15 2TT
United Kingdom
Sponsor information
Organisation
University of Birmingham (UK)
Sponsor details
Edgbaston
Birmingham
B15 2TT
England
United Kingdom
Sponsor type
University/education
Website
ROR
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
Paper on the primary endpoint data for PV patients is in progress. We will also be planning for a final paper on ET patients, this cohort of patients completed follow up in Feb-2020. Further publications will be forthcoming after follow up is complete for all patients and the end of trial report is produced in 2022. (added 20/07/2020)
Intention to publish date
28/03/2023
Individual participant data (IPD) sharing plan
The datasets generated during and/or analysed during the current study are/will be available upon request from the Trial Management Group (contact majic@trials.bham.ac.uk) who will review any requests for data sharing following the end of trial report in 2022.
IPD sharing plan summary
Available on request
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Plain English results | 25/10/2022 | No | Yes | ||
| Basic results | 29/03/2023 | 29/03/2023 | No | No | |
| HRA research summary | 28/06/2023 | No | No | ||
| Results article | 01/07/2023 | 30/06/2023 | Yes | No |