ThrombocythemiaPT-1NCT00175838
Primary Thrombocythaemia 1 Trial
A study testing Hydroxyurea and Aspirin in people with Thrombocythemia and Myeloproliferative Disorder, run by University of Cambridge at 1 site in United Kingdom.
Trial summary
The purpose of this trial is to see if Hydroxyurea + aspirin is a better treatment than aspirin alone for Intermediate Risk Primary Thrombocythemia (PT) patients. Read more about this study
- Who is it for?
- Ages 40 to 59 years
- Conditions the study is for
- Thrombocythemia, Myeloproliferative Disorder
- What is being tested?
- Hydroxyurea and Aspirin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,398 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Jul 1997to Nov 2016
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 59 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- The proposal is to include as many patients with PT as possible including previously diagnosed patients whether or not they have received treatment. Thus all patients are eligible assuming they meet the diagnostic criteria and they do not have any exclusion criterion (see below). It will be necessary to stratify patients according to their previous treatment. This information will be collected on entry to the study. Informed consent is of course required where there is a change of therapeutic strategy.
- The diagnostic criteria for primary thrombocythaemia are:
- Platelet count > 600x109/l.
- No evidence of overt polycythaemia(confirmed by RCM if necessary)or of polycythaemia masked by co-existent iron deficiency.
- No Philadelphia chromosome.
- Absence of peripheral blood and/or marrow appearances of myelodysplasia, or myelofibrosis.
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- No known cause of reactive thrombocytosis. Particular care should be taken to exclude iron deficiency in pre-menopausal women.
- Notes:
- In asymptomatic patients, the platelet count should be observed for a period of at least 2 months to confirm >600x109/l, and to allow any cause of reactive thrombocytosis to become overt.
- If the PCV is above normal upper limit (that is, males >0.51, females >0.48) or in high normal range in a patient with palpable splenomegaly measure RCM. Iron deficient primary polycythaemia (polycythaemia vera) is strongly suggested if Hb/PCV is normal in the presence of iron deficient red cell changes. In this situation, iron therapy is potentially dangerous.
- Exceeding rarely, bcr-abl positive Philadelphia chromosome negative patients present with high platelet counts with little or no elevation in WBC count. The features that suggest it is necessary to examine for bcr-abl, are:- basophilia, left-shift in WBC, granulocyte count >16x109/l, difficulty in controlling platelet count, megakaryocytes of low ploidy (NAP is usually unhelpful).
- A normal ESR, CRP or plasma viscosity is useful in excluding a reactive thrombocytosis.
- Written informed consent obtained in accordance with NCRI requirements.
- Patients with impaired hepatic / renal function are not excluded although the respective biochemical tests should be monitored during therapy and reduced doses of cytoreductive agent should be used, particularly in the case of hydroxyurea and renal dysfunction.
Who cannot join
- High risk features (any of the following):
- Age >or= 60 years
- Platelet count > or= 1500x109/l (current or previous) (a)
- History of ischaemia, thrombosis or embolic events (including erythromelalgia) (b)
- Haemorrhage considered to be related to PT (b)
- Presence of hypertension (c)or diabetes (d)
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- The manufacturers of hydroxyurea state that it should be avoided in pregnancy and in lactating women. Similarly, hydroxyurea should not be prescribed for women when there is doubt about their use of an effective contraceptive method.
- Exclude patient from hydroxyurea therapy and, therefore, from the 'intermediate' risk randomisation if the patient has current leg ulcers.
- Notes on the definition of high risk:
- In patients with borderline counts the allocation of a patient to a high risk group based on platelet count alone should rely on at least three samples taken on separate occasions over at least 2 months.
- Documentation of previous thrombo-embolic, ischaemic and haemorrhagic events should be given on the patient's entry proforma.
- Hypertension is defined as those patients requiring hypotensive therapy.
- Diabetes is defined as those patients requiring therapy with a hypoglycaemic agent.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomised Trial to Compare Aspirin vs Hydroxyurea/Aspirin in 'Intermediate Risk' Primary Thrombocythaemia and Aspirin Only With Observation in 'Low Risk'Primary Thrombocythaemia
The purpose of this trial is to see if Hydroxyurea + aspirin is a better treatment than aspirin alone for Intermediate Risk Primary Thrombocythemia (PT) patients.
Read the detailed description
The myeloproliferative disease, primary thrombocythaemia (PT), has a median age of presentation of 60 years but is increasingly being recognised at an earlier age. The risks of the untreated condition are micro-vascular and major vessel occlusive events and haemorrhage. Older patients and those with a previous thrombosis are particularly prone to experience a significant vascular occlusive event. An anti-aggregating agent, such as aspirin, has been shown to reduce/alleviate minor ischaemic symptoms. Therefore, except in patients with haemorrhagic symptoms, peptic ulceration and known side-effects to aspirin, the use of low-dose aspirin is appropriate.
Myelofibrotic and acute leukaemic transformations can be long-term complications of PT. The ability of therapeutic agents to delay myelofibrosis or reduce/increase the incidence of acute leukaemia in prospective studies is unknown. However, examination of retrospective data provides anxiety about the leukaemogenic risk of the commonly used cytoreductive agent, hydroxyurea. From an analysis of a few relatively small studies of primary thrombocythaemia, the incidence of acute leukaemic transformation in selected patients treated with hydroxyurea has been given as 5-10% over 4-11 years (1).
Based on the risk factors for vascular occlusion, older patients with a thrombotic history and high platelet count can be separated into a 'high' risk group. There is evidence from a randomised prospective study of 'high-risk' patients that cytoreduction with hydroxyurea significantly reduces vascular occlusion (2). The observed reduction in this prospective study of 29 months median duration was from 24% for those not given cytoreductive treatment to 3.6% for those receiving hydroxyurea - approximately a six-fold reduction. In another prospective study where all patients received hydroxyurea, an incidence of major thrombotic events was 5.6%/year (3). In these high-risk patients, cytoreductive treatment should therefore be given. The high risk arm of the PT1 trial, which has now closed, assessed the cytoreductive treatment of choice for these high risk patients and the results suggest that hydroxyurea plus aspirin is superior to anagrelide plus aspirin (4).
In the patients at lower risk of vascular occlusion the dilemma is that the risk of vascular occlusion in untreated patients is relatively low, but includes major life-threatening events. In two small prospective studies of these patients not receiving platelet lowering agents, the observed major complications were 3% and 4.1% per year and the total complications were 5.1% and 10.5% per year respectively (1). Cyto-reductive treatment should prevent such events and one could predict a similar reduction in complications as seen in the high-risk patients. However, there is evidence that in patients under the age of 40 years the complication rate is only one quarter of that seen in patients aged 40 - 59 years (5). Therefore it has been decided to divide these patients at lower risk of vascular occlusion into 'intermediate' and 'low risk' groups. Patients aged 40-59 years will fall into the 'intermediate risk' group and will be randomised to cytoreduction or not, while all will receive aspirin. Patients under 40 years will form the 'low-risk' group and will receive aspirin alone. Cyto-reductive treatment might also delay myelofibrotic transformation as observed in primary polycythaemia. However, this benefit and the possible reduction in vaso-occlusive episodes need to be balanced against the potential long-term risk of increasing acute leukaemic transformation.
- Conditions
- Thrombocythemia, Myeloproliferative Disorder
- Being tested
- Hydroxyurea, Aspirin
- Keywords
- Primary Thrombocythmeia, Hydroxyurea, Randomised, Thrombosis, Haemorrhage
- Medical subject headings
- Thrombocytosis, Myeloproliferative Disorders, Thrombosis, Hemorrhage
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HydroxyureaDrug
Also called Hydroxycarbamide
Hydroxyurea (or hydroxycarbamide) is an antineoplastic drug commonly used to treat haematological malignancies.
AspirinDrug
Aspirin is an anti-aggregating agent, and has been shown to reduce/alleviate minor ischaemic symptoms.
| Study group | Role | What they receive |
|---|---|---|
| Intermediate risk group | Active comparator | Intermediate risk patients are randomised to a either a group receiving Aspirin only, or a group receiving both Hydroxyurea and Aspirin. Receives: Drug: Hydroxyurea; Drug: Aspirin |
| Low risk group | Active comparator | Patients are given Aspirin only with observation. Receives: Drug: Aspirin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Does hydroxyurea reduce thrombosis and major haemorrhage when added to aspirin?
Reducing thrombosis and major haemorrhage are specific key measurements in this group of patients for whom thrombotic events are very likely to occur.
Measured: 14 years
Secondary outcomes (1)
Does treatment modality alter the risk of leukaemic or myelofibrotic transformation?
Measured: 14 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Sep 2005 (estimated)
- Study startJul 1997
- Primary completionNov 2016
- Study completionNov 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for ThrombocythemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 1,398 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Cambridge
- Sponsor type
- University, hospital or other
- Collaborators
- Cambridge University Hospitals NHS Foundation Trust, Institute of Cancer Research, United Kingdom
- Responsible party
- Principal investigator, Anthony Green, University of Cambridge
- Investigators
- Anthony R Green, Prof, Study director, Addenbrooke's Hospital and University of CambridgeClaire Harrison, Dr, Principal investigator, St Thomas' Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00175838
- Sponsor's protocol ID
- A05033
- Other IDs
- EUdraCT no:2004-000245-38, ISRCTN: 72251782
- Acronym
- PT-1
- Status last verified
- Jan 2017
- First submitted
- 9 Sep 2005
- Last updated
- 18 Jan 2017
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Godfrey AL, Campbell PJ, MacLean C, Buck G, Cook J, Temple J, Wilkins BS, Wheatley K, Nangalia J, Grinfeld J, McMullin MF, Forsyth C, Kiladjian JJ, Green AR, Harrison CN; United Kingdom Medical Research Council Primary Thrombocythemia-1 Study; United Kingdom National Cancer Research Institute Myeloproliferative Neoplasms Subgroup; French Intergroup of Myeloproliferative Neoplasms; the Australasian Leukaemia and Lymphoma Group.. Hydroxycarbamide Plus Aspirin Versus Aspirin Alone in Patients With Essential Thrombocythemia Age 40 to 59 Years Without High-Risk Features. J Clin Oncol. 2018 Dec 1;36(34):3361-3369. doi: 10.1200/JCO.2018.78.8414. Epub 2018 Aug 28.
PubMed 30153096
Study at a glance
From the registry record, last updated by the sponsor on 18 Jan 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised Trial to Compare Aspirin vs Hydroxyurea/Aspirin in 'Intermediate Risk' Primary Thrombocythaemia and Aspirin Only With Observation in 'Low Risk'Primary Thrombocythaemia
- ClinicalTrials.gov ID
- NCT00175838
- Acronym / sponsor ID
- PT-1 / A05033
- Conditions
- Thrombocythemia, Myeloproliferative Disorder
- Keywords
- Primary Thrombocythmeia, Hydroxyurea, Randomised, Thrombosis, Haemorrhage
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,398 participants (actual)
- Lead sponsor
- University of CambridgeUniversity, hospital or other
- Collaborators
- Cambridge University Hospitals NHS Foundation Trust, Institute of Cancer Research, United Kingdom
- Study start
- Jul 1997
- Primary completion
- Nov 2016 (actual)
- Study completion
- Nov 2016 (actual)
- First posted
- 15 Sep 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this trial is to see if Hydroxyurea + aspirin is a better treatment than aspirin alone for Intermediate Risk Primary Thrombocythemia (PT) patients.
Detailed description
The myeloproliferative disease, primary thrombocythaemia (PT), has a median age of presentation of 60 years but is increasingly being recognised at an earlier age. The risks of the untreated condition are micro-vascular and major vessel occlusive events and haemorrhage. Older patients and those with a previous thrombosis are particularly prone to experience a significant vascular occlusive event. An anti-aggregating agent, such as aspirin, has been shown to reduce/alleviate minor ischaemic symptoms. Therefore, except in patients with haemorrhagic symptoms, peptic ulceration and known side-effects to aspirin, the use of low-dose aspirin is appropriate.
Myelofibrotic and acute leukaemic transformations can be long-term complications of PT. The ability of therapeutic agents to delay myelofibrosis or reduce/increase the incidence of acute leukaemia in prospective studies is unknown. However, examination of retrospective data provides anxiety about the leukaemogenic risk of the commonly used cytoreductive agent, hydroxyurea. From an analysis of a few relatively small studies of primary thrombocythaemia, the incidence of acute leukaemic transformation in selected patients treated with hydroxyurea has been given as 5-10% over 4-11 years (1).
Based on the risk factors for vascular occlusion, older patients with a thrombotic history and high platelet count can be separated into a 'high' risk group. There is evidence from a randomised prospective study of 'high-risk' patients that cytoreduction with hydroxyurea significantly reduces vascular occlusion (2). The observed reduction in this prospective study of 29 months median duration was from 24% for those not given cytoreductive treatment to 3.6% for those receiving hydroxyurea - approximately a six-fold reduction. In another prospective study where all patients received hydroxyurea, an incidence of major thrombotic events was 5.6%/year (3). In these high-risk patients, cytoreductive treatment should therefore be given. The high risk arm of the PT1 trial, which has now closed, assessed the cytoreductive treatment of choice for these high risk patients and the results suggest that hydroxyurea plus aspirin is superior to anagrelide plus aspirin (4).
In the patients at lower risk of vascular occlusion the dilemma is that the risk of vascular occlusion in untreated patients is relatively low, but includes major life-threatening events. In two small prospective studies of these patients not receiving platelet lowering agents, the observed major complications were 3% and 4.1% per year and the total complications were 5.1% and 10.5% per year respectively (1). Cyto-reductive treatment should prevent such events and one could predict a similar reduction in complications as seen in the high-risk patients. However, there is evidence that in patients under the age of 40 years the complication rate is only one quarter of that seen in patients aged 40 - 59 years (5). Therefore it has been decided to divide these patients at lower risk of vascular occlusion into 'intermediate' and 'low risk' groups. Patients aged 40-59 years will fall into the 'intermediate risk' group and will be randomised to cytoreduction or not, while all will receive aspirin. Patients under 40 years will form the 'low-risk' group and will receive aspirin alone. Cyto-reductive treatment might also delay myelofibrotic transformation as observed in primary polycythaemia. However, this benefit and the possible reduction in vaso-occlusive episodes need to be balanced against the potential long-term risk of increasing acute leukaemic transformation.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intermediate risk group | Active comparator | Drug: Hydroxyurea, Drug: AspirinIntermediate risk patients are randomised to a either a group receiving Aspirin only, or a group receiving both Hydroxyurea and Aspirin. |
| Low risk group | Active comparator | Drug: AspirinPatients are given Aspirin only with observation. |
Who may qualify
- Ages
- 40 to 59 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (14 listed)
- The proposal is to include as many patients with PT as possible including previously diagnosed patients whether or not they have received treatment. Thus all patients are eligible assuming they meet the diagnostic criteria and they do not have any exclusion criterion (see below). It will be necessary to stratify patients according to their previous treatment. This information will be collected on entry to the study. Informed consent is of course required where there is a change of therapeutic strategy.
- Platelet count > 600x109/l.
- No evidence of overt polycythaemia(confirmed by RCM if necessary)or of polycythaemia masked by co-existent iron deficiency.
- No Philadelphia chromosome.
- Absence of peripheral blood and/or marrow appearances of myelodysplasia, or myelofibrosis.
Key exclusion criteria (13 listed)
- Age >or= 60 years
- Platelet count > or= 1500x109/l (current or previous) (a)
- History of ischaemia, thrombosis or embolic events (including erythromelalgia) (b)
- Haemorrhage considered to be related to PT (b)
- Presence of hypertension (c)or diabetes (d)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HydroxyureaAlso: HydroxycarbamideHydroxyurea (or hydroxycarbamide) is an antineoplastic drug commonly used to treat haematological malignancies. | Drug | Intermediate risk group |
| AspirinAspirin is an anti-aggregating agent, and has been shown to reduce/alleviate minor ischaemic symptoms. | Drug | Intermediate risk group, Low risk group |
Primary outcome
Does hydroxyurea reduce thrombosis and major haemorrhage when added to aspirin?
Time frame: 14 years
Reducing thrombosis and major haemorrhage are specific key measurements in this group of patients for whom thrombotic events are very likely to occur.
1 secondary outcome
Does treatment modality alter the risk of leukaemic or myelofibrotic transformation?
Time frame: 14 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jan 2017.
- Derived from this study: PubMed 30153096Godfrey AL, Campbell PJ, MacLean C, Buck G, Cook J, Temple J, Wilkins BS, Wheatley K, Nangalia J, Grinfeld J, McMullin MF, Forsyth C, Kiladjian JJ, Green AR, Harrison CN; United Kingdom Medical Research Council Primary Thrombocythemia-1 Study; United Kingdom National Cancer Research Institute Myeloproliferative Neoplasms Subgroup; French Intergroup of Myeloproliferative Neoplasms; the Australasian Leukaemia and Lymphoma Group.. Hydroxycarbamide Plus Aspirin Versus Aspirin Alone in Patients With Essential Thrombocythemia Age 40 to 59 Years Without High-Risk Features. J Clin Oncol. 2018 Dec 1;36(34):3361-3369. doi: 10.1200/JCO.2018.78.8414. Epub 2018 Aug 28.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Anthony R Green, Prof study director
Addenbrooke's Hospital and University of Cambridge
Claire Harrison, Dr principal investigator
St Thomas' Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Hydroxyurea and Aspirin in people with Thrombocythemia and Myeloproliferative Disorder, run by University of Cambridge at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Jan 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Does hydroxyurea reduce thrombosis and major haemorrhage when added to aspirin? (time frame: 14 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00175838, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jan 2017.