Best available therapy versus JAK Inhibition in patients with high risk polycythaemia vera or essential thrombocythaemia who are resistant or intolerant to hydroxycarbamide
| ISRCTN | ISRCTN61925716 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN61925716 |
| EudraCT/CTIS number | 2011-005279-18 |
| Secondary identifying numbers | 11941 |
- Submission date
- 12/04/2012
- Registration date
- 12/04/2012
- Last edited
- 30/06/2023
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Cancer
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Plain English Summary
Contact information
Mrs Sonia Fox
Scientific
Scientific
Edgbaston
Birmingham
B15 2TT
United Kingdom
| MAJIC@trials.bham.ac.uk |
Study information
| Study design | Randomised; Interventional; Design type: Treatment |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| 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 |
| Study 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 |
| 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 |
Eligibility
| 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 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 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
B15 2TT
United Kingdom
Sponsor information
University of Birmingham (UK)
University/education
University/education
Edgbaston
Birmingham
B15 2TT
England
United Kingdom
"ROR" |
https://ror.org/03angcq70 |
|---|
Funders
Funder type
Charity
Leukaemia & Lymphoma Research (UK)
No information available
Results and Publications
| Intention to publish date | 28/03/2023 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| 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) |
| 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. |
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 |
Additional files
Editorial Notes
30/06/2023: Publication reference added.
29/03/2023: The basic results have been uploaded as an additional file.
25/10/2022: Cancer Research UK plain English results link added.
14/09/2022: The following changes have been made:
1. The overall trial end date was changed from 30/09/2021 to 28/03/2022.
2. The intention to publish date was changed from 30/09/2022 to 28/03/2023.
29/09/2021: The following changes have been made:
1. The total final enrolment number has been added.
2. The IPD sharing statement has been added and participant level data has been changed from "Not provided at the time of registration" to "Available on request".
05/08/2020: The overall trial end date has been changed from 31/07/2020 to 30/09/2021.
20/07/2020: The following changes were made to the trial record:
1. The publication and dissemination plan was added.
2. The IPD sharing statement was added to the publication and dissemination plan.
3. The intention to publish date was added.
