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Primary Myelofibrosis (PMF)Phase 4MACS2030NCT01558739

Exploratory Phase II Study of INC424 Patients With Primary Myelofibrosis (PMF) or Post Polycythaemia Myelofibrosis (PPV MF) or Post Essential Thrombocythaemia Myelofibrosis (PET-MF)

A Phase 4 study testing INC424 in people with Primary Myelofibrosis (PMF) and Post Polycythaemia Myelofibrosis (PPV MF), run by Novartis Pharmaceuticals at 10 sites in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The primary objective of this study is to evaluate the efficacy of INC424 in patients with PMF, PPV MF, or PET-MF using a composite measure of either an objective endpoint (> 50% reduction in splenomegaly using palpitation at 48 weeks) and/or a subjective endpoint (>50% reduction in total symptom score at 48 weeks). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
INC424
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
48 participants
Where
10 sitesUnited Kingdom
Study dates
May 2012to Jan 2014
Phase
Phase 4
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients must not be eligible for another ongoing INC424 clinical trial.
  • Patients must be diagnosed with PMF, PPV MF or PET-MF, according to the 2008 revised World Health Organization criteria irrespective of JAK2 mutation status.
  • Patients with PMF requiring therapy must be classified as high risk (3 prognostic factors) OR intermediate risk level 2 (2 prognostic factors, no more), OR intermediate risk level 1 (1 prognostic factor, no more) with an enlarged spleen. The prognostic factors, defined by the International Working Group are:
  • Age > 65 years;
  • Presence of constitutional symptoms (weight loss, fever, night sweats); marked anemia (Hgb < 10g/dL)*;
  • Leukocytosis (history of WBC > 25 x109/L);
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  • Circulating blasts > 1%. • A hemoglobin value < 10 g/dL must be demonstrated during the Screening Visit for patients who are not transfusion dependent. Patients receiving regular transfusions of packed red blood cells will be considered to have hemoglobin < 10 g/dL for the purpose of evaluation of risk factors.
  • Patients with Intermediate-1 disease and splenomegaly must have a palpable spleen measuring 5 cm or greater from the costal margin to the point of greatest splenic protrusion.
  • Patients must have a peripheral blood blast count of < 10%.
  • Patients with adequate liver function defined as direct bilirubin ≤ 2.0 x ULN and ALT ≤ 2.5 x ULN.
  • Patients with adequate renal function defined as serum creatinine ≤ 2 x ULN.
  • Patients with an ECOG performance status of 0, 1, or 2 (Appendix 5).

Who cannot join

  • Patients eligible for hematopoietic stem cell transplantation (suitable candidate and a suitable donor is available).
  • Patients with history of malignancy in past 3 years except for treated, early-stage squamous or basal cell carcinoma in situ.
  • Patients undergoing treatment with hematopoietic growth factor receptor agonists (i.e., erythropoietin [Epo], granulocyte colony stimulating factor (GCSF [Neupogen; Neulasta], romiplostim, eltrombopag) at any time within 2 weeks prior to Screening or 4 weeks prior to Baseline.
  • Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral INC424 (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection).
  • Patients with cardiac disease which in the Investigator's opinion may jeopardize the safety of the patient or the compliance with the protocol.
  • Patients with clinically significant bacterial, fungal, parasitic or viral infection which require therapy. Patients with acute bacterial infections requiring antibiotic use should delay screening/enrollment until the course of antibiotic therapy has been completed.
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  • Patients with known active hepatitis A, B, C or who are HIV-positive.
  • Patients with inadequate bone marrow reserve as demonstrated by:
  • Absolute neutrophil count (ANC) that is ≤ 1000/µL.
  • Platelet count that is < 100,000/µL without the assistance of growth factors, thrombopoietic factors or platelet transfusions.
  • Patients with any history of platelet counts < 50,000/µL or ANC < 500/µL except during treatment for a myeloproliferative disorder or treatment with cytotoxic therapy for any other reason.
  • Patients with coagulation parameters (PT, PTT, INR) ≥ 1.5.
  • Patients with known hypersensitivity to INC424 or other JAK1/2 inhibitors, or to their excipients.
  • Patients under ongoing treatment with another investigational medication or having been treated with an investigational medication within 30 days of screening.
  • Patients with any concurrent condition that, in the Investigator's opinion would jeopardize the safety of the patient or compliance with the protocol.
  • Other protocol-defined inclusion/exclusion criteria may apply.

Trial locations and contacts

10 sites in 1 country.

10 sites in 1 country

United Kingdom10 sites

  • Novartis Investigative Site

    Bournemouth, BH7 7DW

  • Novartis Investigative Site

    Cardiff, Wales, CF14 4XN

  • Novartis Investigative Site

    East Yorkshire, HU16 5JQ

  • Novartis Investigative Site

    Edinburgh, EH4 2XU

  • Novartis Investigative Site

    Leicester, LE7 5WW

  • Novartis Investigative Site

    Liverpool, L7 8XP

  • Novartis Investigative Site

    London, SE1 9RT

  • Novartis Investigative Site

    London, W12 0HS

  • Novartis Investigative Site

    Manchester, M13 9NT

  • Novartis Investigative Site

    Oxford, OX3 7LJ

Other trials in United Kingdom

About this study

Official title: A UK Open-label, Multicentre, Exploratory Phase II Study of INC424 for Patients With Primary Myelofibrosis (PMF) or Post Polycythaemia Myelofibrosis (PPV MF) or Post Essential Thrombocythaemia Myelofibrosis (PET-MF)

The primary objective of this study is to evaluate the efficacy of INC424 in patients with PMF, PPV MF, or PET-MF using a composite measure of either an objective endpoint (> 50% reduction in splenomegaly using palpitation at 48 weeks) and/or a subjective endpoint (>50% reduction in total symptom score at 48 weeks).

Being tested
INC424
Keywords
Ruxolitinib, INC424, myelofibrosis, PMF, post polycythemia myelofibrosis, PPV MF, post-essential thrombocythemia myelofibrosis, PET-MF, Primary Myelofibrosis, Polycythemia, Thrombocythemia, Essential Thrombocytosis, myeloproliferative Disorders, Bone Marrow Diseases, Haematologic Diseases, Blood Coagulation Disorders, Blood Platelet Disorders, Haemorrhagic Disorders
Medical subject headings
Primary Myelofibrosis, Polycythemia, Thrombocytosis, Thrombocythemia, Essential, Myeloproliferative Disorders, Bone Marrow Diseases, Blood Coagulation Disorders, Blood Platelet Disorders

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • INC424Drug

    Ruxolitinib was provided in 5 mg tablets, packaged in bottles. 15 - 20 mg (dose based on Baseline platelet count) twice daily.

Study groups in NCT01558739
Study groupRoleWhat they receive
INC424ExperimentalPatients diagnosed with PMF, PPV MF, or PET-MF were treated with oral INC424 at a dose of 15 - 20 mg (dose based on Baseline platelet count) twice daily.
Receives: Drug: INC424

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of Participants With Treatment Success

    Treatment success was defined as a 50% or greater reduction in palpable spleen length versus baseline at 48 weeks and/or a 50% or greater improvement in total symptom score (derived from the MF symptom assessment form (MFSAF) questionnaire) versus baseline at the week 48 time point. The MFSAF assesses the following symptoms (all scored from absent (0) to worst imaginable (10)): general fatigue, abdominal pain (and discomfort), inactivity (ability to move and walk around), cough, night sweats, itching (pruritus), bone pain (diffuse not joint pain or arthritis), fever, change in appetite/unintentional weight loss (or gain) in past 6 months, overall quality of life (QoL).

    Measured: 48 Weeks

Secondary outcomes (8)

  1. Percentage of Participants With Best Overall Response

    Response to treatment and disease progression was assessed by physical examination, specifically assessing changes in spleen size by palpation. Disease response and progression was evaluated using the International Working Group for myelofibrosis Research and Treatment Response Criteria.

    Measured: week 48

  2. Change From Baseline in Myelofibrosis Symptoms Assessment Form (MF-SAF)

    The MF-SAF consists of seven questions about key symptoms and impact of MF. Questions are scored on a scale of 0-10, with higher scores indicating more severe symptoms and greater inactivity. Questions 1-6, which together comprise a Total Symptom Score (TSS), investigate the following symptoms: night sweats, pruritus/itching, abdominal discomfort, pain under the ribs, early satiety and bone/muscle pain. Question 7 asks patients to report levels of inactivity. The TSS reflects the sum of the scores of these symptoms excluding inactivity, with the maximum possible score being 60 (most severe symptom experienced).

    Measured: Baseline, week 4, week 12, week 24, week 48

  3. Change From Baseline in EQ5D Preference Index (5 Level EuroQol Questionnaire Determining Quality of Life) From Baseline

    The EQ-5D is a standardized instrument used for measuring health outcomes in a wide range of health conditions and treatment. It consists of a descriptive system and a visual analogue scale (EQ-VAS). The descriptive system comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 3 levels: no problems, some problems, and extreme problems. The EQ-VAS records the participant's self-rated health on a vertical, VAS where the endpoints are labeled 'best imaginable health state' and 'worst imaginable health state'. The EQ-5D health state was converted to a single summary index by applying a formula that attaches a weight to each of the levels in each dimension. The final EQ5D preference index scores range from 0 to 1 with higher scores indicating better health.

    Measured: Baseline, week 4, week 12, week 24, week 48

  4. Number of Hospitalizations

    Medical resource utilization (MRU) was assessed according to the number of hospitalizations.

    Measured: week 12, week 24, week 26, week 48

  5. Duration of Hospitalizations

    MRU was assessed according to the mean duration of hospitalization visits.

    Measured: week 48

  6. Number of Accident & Emergency Visits From Baseline

    MRU was assessed according to the number of accidents and emergency room visits.

    Measured: baseline to week 12, week 12 to week 24, week 24 to week 36, week 36 to week 48

  7. Number of General Practitioner (GP), Specialists' and Urgent Care Visits

    MRU was assessed according to the number of GP, specialists', and urgent care visits.

    Measured: baseline to week 12, week 12 to, week 24, week 24 to week 36, week 36 to week 48

  8. Percentage of Participants With Transfusion Dependency Status

    Transfusion dependency status from baseline through the end of study was assessed. New onset of transfusion dependency was defined as the use of 2 or more units of red blood cell products during the 8 weeks prior to a study visit. New onset of transfusion independency was defined as the use of 0 or 1 unit of red blood cell products during the 8 weeks prior to a study visit.

    Measured: baseline (BL), end of treatment (up to 28 days post last treatment) (EOT)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Mar 2012 (estimated)
  2. Study startMay 2012
  3. Primary completionJan 2014
  4. Study completionJan 2014

Resources

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 4
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
48 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01558739
Sponsor's protocol ID
CINC424AGB02
Other IDs
2011-005066-38
Acronym
MACS2030
Status last verified
Mar 2015
First submitted
16 Mar 2012
Last updated
3 Mar 2015
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing INC424 in people with Primary Myelofibrosis (PMF) and Post Polycythaemia Myelofibrosis (PPV MF), run by Novartis Pharmaceuticals at 10 sites 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 12 inclusion and 16 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 3 Mar 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 sites 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.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 3 Mar 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Percentage of Participants With Treatment Success (time frame: 48 Weeks). 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 NCT01558739.

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 3 Mar 2015.

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