Primary MyelofibrosisPhase 2REALISENCT02966353
Efficacy and Safety of Ruxolitinib in the Treatment of Anemic Myelofibrosis Patients.
A Phase 2 study testing ruxolitinib in people with Primary Myelofibrosis and Post-Polycythemia Vera-Myelofibrosis, run by Novartis Pharmaceuticals at 20 sites in 11 countries.
Trial summary
This was a study of treatment with ruxolitinib in patients who presented with transfusion dependent or independent anemia. Starting dose was 10 mg BID. This dose was maintained for the first 12 weeks of the study and up-titrated thereafter unless the subject met criteria for dose hold or dose reduction Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Primary Myelofibrosis, Post-Polycythemia Vera-Myelofibrosis, Post-Essential Thrombocythemia Myelofibrosis
- What is being tested?
- ruxolitinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 51 participants
- Where
- 20 sitesin 11 countries
- Study dates
- 31 Mar 2017to 15 Feb 2019
- Phase
- Phase 2
- 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
- Written informed consent must be obtained prior to any screening procedures.
- Male or female patients aged ≥ 18 years of age.
- Patients must have been diagnosed with PMF, according to the 2016 revised International Standard Criteria, PPV MF or PET-MF, irrespective of JAK2 mutation status.
- Patients must have had palpable splenomegaly that is equal to or greater than 5 cm below the left costal margin.
- Patients must have had hemoglobin less than 10 g/dL
- Patients must have had a history of transfusions must have a documented transfusion record in the previous 12 weeks to baseline.
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- Patients must have had ECOG performance status of 0, 1, or 2.
- Patients must have had a peripheral blood blast percentage count of < 10%.
- Patients must have recovered or stabilized sufficiently from any adverse drug reactions associated with prior treatments before beginning treatment with ruxolitinib.
Who cannot join
- Patients who had prior treatment with any JAK1 or JAK2 inhibitor.
- Patients who had known hypersensitivity to ruxolitinib or other JAK1/JAK2 inhibitors, or to their excipients.
- Patients who had been eligible for hematopoietic stem cell transplantation (suitable candidate and a suitable donor is available).
- Patients who had inadequate bone marrow reserve at baseline as demonstrated by at least one of the following:
- ANC that is ≤ 1,000/µL.
- Platelet count that is <50,000/µL without the assistance of growth factors, thrombopoietic factors or platelet transfusions.
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- Hemoglobin count that is ≤ 6.5 g/dL despite transfusions.
- Patients who had severely impaired renal function defined by: Creatinine clearance less than 30 mL/min.
- Patients who had inadequate liver function defined by any of these:
- Total bilirubin ≥ 2.5 x ULN and subsequent determination of direct bilirubin ≥ 2.5 x ULN;
- Alanine aminotransferase (ALT) > 2.5 x ULN;
- Aspartate aminotransferase (AST) > 2.5 x ULN.
- Patients who were being treated concurrently with a strong (potent) systemic inhibitor or inducer of CYP3A4 at the time of Screening.
- Presence of active bacterial, fungal, parasitic, or viral infection which requires therapy.
- Known history of human immunodeficiency virus (HIV) infection or other immunodeficiency syndromes such as X-linked agammaglobulinemia and common variable immune deficiency.
- Acute viral hepatitis or active chronic hepatitis B or C infection. Patients with inactive chronic infection (without viral replication) can be enrolled
- History of progressive multifocal leuko-encephalopathy.
- Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of ruxolitinib .
- History or current diagnosis of uncontrolled or significant cardiac disease, including any of the following:
- Myocardial infarction within last 6 months
- Uncontrolled congestive heart failure
- Unstable angina within last 6 months
- Clinically significant (symptomatic) cardiac arrhythmias (e.g. bradyarrhythmias, sustained ventricular tachycardia, and clinically significant second or third degree AV block without a pacemaker)
- Significant concurrent, uncontrolled medical condition which, in the investigator's opinion, would have jeopardized the safety of the patient or compliance with the protocol.
- Patients who were undergoing treatment with another investigational medication or had been treated with an investigational medication within 30 days or 5 half-lives (whichever is longer) prior to the first dose of study drug.
- Patients who had a history of malignancy in the past 3 years, except for treated early stage squamous or basal cell carcinoma.
- Patients who were unable to comprehend or are unwilling to sign an ICF.
- Pregnant or nursing (lactating) women
- Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they were using highly effective methods of contraception throughout the study duration inclusive of 30 day safety follow up.
Trial locations and contacts
20 sites in 11 countries.
20 sites in 11 countries
Italy3 sites
Novartis Investigative Site
Bologna, BO, 40138
Novartis Investigative Site
Florence, FI, 50134
Novartis Investigative Site
Palermo, PA, 90127
Russia3 sites
Novartis Investigative Site
Moscow, 125167
Novartis Investigative Site
Moscow, 129110
Novartis Investigative Site
Petrozavodsk, 185019
Spain3 sites
Novartis Investigative Site
Alicante, Valencia, 03010
Novartis Investigative Site
Barcelona, Catalonia, 08036
Novartis Investigative Site
Santiago de Compostela, Galicia, 15706
Belgium2 sites
Novartis Investigative Site
Antwerp, 2060
Novartis Investigative Site
Leuven, 3000
Bulgaria2 sites
Novartis Investigative Site
Sofia, 1413
Novartis Investigative Site
Sofia, 1756
Turkey (Türkiye)2 sites
Novartis Investigative Site
Istanbul, 34093
Novartis Investigative Site
Kocaeli, 41380
About this study
Official title: A Multicenter Phase II, Open Label, Single Arm Study to Evaluate the Efficacy and Safety of Ruxolitinib in the Treatment of Anemic Myelofibrosis Patients.
This was a study of treatment with ruxolitinib in patients who presented with transfusion dependent or independent anemia. Starting dose was 10 mg BID. This dose was maintained for the first 12 weeks of the study and up-titrated thereafter unless the subject met criteria for dose hold or dose reduction
Read the detailed description
This was a study of treatment with ruxolitinib in patients who present with transfusion dependent or independent anemia at screening defined as an hemoglobin <10 g/dL with 10 mg BID starting dose with subsequent up titrations (maximum dose 25 mg BID) depending on safety and efficacy. This dosing approach for anemic MF patients will be systematically studied in this prospective multicenter phase II open label single arm trial to determine if the levels of spleen length reduction and symptom improvement are consistent with those reported in previous clinical trials with ruxolitinib in patients with anemia and doses according to platelet counts at the moment of treatment initiation, and whether this lower starting dose and up titration approach may minimize the initial hemoglobin and platelet declines and transfusion requirements.
- Conditions
- Primary Myelofibrosis, Post-Polycythemia Vera-Myelofibrosis, Post-Essential Thrombocythemia Myelofibrosis
- Being tested
- ruxolitinib
- Keywords
- Ruxolitinib, anemia, Primary Myelofibrosis, PMF, Post-Polycythemia Vera-Myelofibrosis, PPV-MF, Post-Essential Thrombocythemia Myelofibrosis, PET-MF, adult, INC424
- Medical subject headings
- Primary Myelofibrosis, Anemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ruxolitinibDrug
Ruxolitinib was supplied in 5 mg tablets to be taken orally approximately 12 hours apart (morning and night)
| Study group | Role | What they receive |
|---|---|---|
| All Subjects | Experimental | 10 mg BID (2 tablets of 5mg) was self-administered as starting dose for all patients. This dose was maintained for the first 12 weeks and titrated up thereafter unless they had met criteria for dose hold or dose reduction. Dose was to have been increased or decreased per standardized dosing paradigm and not to have exceeded 25 mg bid. Receives: Drug: ruxolitinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With at Least 50% Reduction in Spleen Length From Baseline at Week 24
Percentage of participants achieving a 50% reduction in spleen length at week 24. For subjects with palpable spleen at baseline and non-palpable at post-baseline, the post-baseline spleen are imputed as 0. Subjects who had palpable, but missing spleen length at baseline is excluded from the analysis. Subjects with missing spleen length at Week 24 or who withdraw earlier from the study are considered as a non-responder. The 95% CI is computed using exact Clopper-Pearson method.
Measured: Baseline up to week 24
Secondary outcomes (5)
Percentage of Participants With at Least 50% Reduction in Spleen Length From Baseline at Week 48
Percentage of participants achieving a 50% reduction in spleen length at week 48. For subjects with palpable spleen at baseline and non-palpable at post-baseline, the post-baseline spleen is imputed as 0. Subjects who had palpable, but missing spleen length at baseline is excluded from the analysis. Subjects with missing spleen length at Week 48 or who withdraw earlier from the study are considered as a non-responder. The 95% CI is computed using exact Clopper-Pearson method.
Measured: Baseline up to week 48
Percentage of Participants by Spleen Length Reduction or no Increase From Baseline Category at Week 24 and Week 48
Participants who achieved a ≤ 50% reduction in spleen length at week 24 and 48 (reduction) and participants who had no increase greater than or equal to 50% (increase). The edge of the spleen shall be determined by palpation, measured in centimeters, using a soft ruler, from the costal margin to the point of greatest splenic protrusion. For subjects with palpable spleen at baseline and non-palpable at post-baseline, the post-baseline spleen is imputed as 0.
Measured: baseline, weeks 24 and 48
Percentage of Participants With at Least a 50% Reduction in Myelofibrosis 7 Item Symptom Scale (MF-7) and Myelofibrosis Symptom Assessment Form (MFSAF) at Week 24
The MF-7 is a disease specific questionnaire comprised of 7 items that measures the severity of seven of the most prevalent associated symptoms including: tiredness, early satiety, abdominal discomfort, night sweats, itching (pruritus), bone pain (diffuse not joint or arthritis) and pain under ribs on left side. Each item was scored on a scale ranging from 0 (absent) to 10 (worst imaginable). The MF-7 score is computed as the sum of the observed scores in the individual items to achieve a 0 to 70 score. There would be one recall period of 24 hours used in this questionnaire. A separate question on Inactivity was to be measured for severity of this symptom on a scale from 0 (absent) to 10 (worst imaginable). This would allow the computation of the MFSAF v2.0 questionnaire results, as 6 out of 7 items in the latter PRO are in overlap with MF7 (they also share same 0-10 range Likert scale and ascending order, absent to worst imaginable).
Measured: Baseline and week 24
Patient Global Impression of Change (PGIC) at Week 24 and Week 48
The PGIC is comprised of a single question intended to measure a subject's perspective of improvement or deterioration over time relative to treatment. The PGIC uses a seven-point scale where '1' equals very much improved and '7' equals very much worse.
Measured: Baseline up to week 48
Percentage of Participants Transfusion Independency From Baseline up to Week 96
Percentage is based on number of subjects who are transfusion dependent at baseline. Transfusion dependence (TD) is defined as subjects receiving 6 or more units of transfusions 12 weeks prior to baseline. Transfusion independence (TI) rate is defined as subjects who are transfusion dependent at baseline and require no unit of transfusion for ≥ 12 weeks at any time during the study.
Transfusion response rate is defined as subjects who are TD at baseline and have 5 or less units of transfusion for ≥ 12 weeks at any time during the study.
Measured: Baseline up to week 96
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Nov 2016 (estimated)
- Study start31 Mar 2017
- Primary completion24 Jul 2018
- Study completion15 Feb 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Primary MyelofibrosisStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 51 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02966353
- Sponsor's protocol ID
- CINC424A2411
- Acronym
- REALISE
- Status last verified
- Apr 2020
- First submitted
- 18 Oct 2016
- Last updated
- 30 Apr 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
Study at a glance
From the registry record, last updated by the sponsor on 30 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter Phase II, Open Label, Single Arm Study to Evaluate the Efficacy and Safety of Ruxolitinib in the Treatment of Anemic Myelofibrosis Patients.
- ClinicalTrials.gov ID
- NCT02966353
- Acronym / sponsor ID
- REALISE / CINC424A2411
- Conditions
- Primary Myelofibrosis, Post-Polycythemia Vera-Myelofibrosis, Post-Essential Thrombocythemia Myelofibrosis
- Keywords
- Ruxolitinib, anemia, Primary Myelofibrosis, PMF, Post-Polycythemia Vera-Myelofibrosis, PPV-MF, Post-Essential Thrombocythemia Myelofibrosis, PET-MF
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 51 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 31 Mar 2017 (actual)
- Primary completion
- 24 Jul 2018 (actual)
- Study completion
- 15 Feb 2019 (actual)
- First posted
- 17 Nov 2016 (estimated)
- Results
- Posted 30 Apr 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This was a study of treatment with ruxolitinib in patients who presented with transfusion dependent or independent anemia. Starting dose was 10 mg BID. This dose was maintained for the first 12 weeks of the study and up-titrated thereafter unless the subject met criteria for dose hold or dose reduction
Detailed description
This was a study of treatment with ruxolitinib in patients who present with transfusion dependent or independent anemia at screening defined as an hemoglobin <10 g/dL with 10 mg BID starting dose with subsequent up titrations (maximum dose 25 mg BID) depending on safety and efficacy. This dosing approach for anemic MF patients will be systematically studied in this prospective multicenter phase II open label single arm trial to determine if the levels of spleen length reduction and symptom improvement are consistent with those reported in previous clinical trials with ruxolitinib in patients with anemia and doses according to platelet counts at the moment of treatment initiation, and whether this lower starting dose and up titration approach may minimize the initial hemoglobin and platelet declines and transfusion requirements.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| All Subjects | Experimental | Drug: ruxolitinib10 mg BID (2 tablets of 5mg) was self-administered as starting dose for all patients. This dose was maintained for the first 12 weeks and titrated up thereafter unless they had met criteria for dose hold or dose reduction. Dose was to have been increased or decreased per standardized dosing paradigm and not to have exceeded 25 mg bid. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Written informed consent must be obtained prior to any screening procedures.
- Male or female patients aged ≥ 18 years of age.
- Patients must have been diagnosed with PMF, according to the 2016 revised International Standard Criteria, PPV MF or PET-MF, irrespective of JAK2 mutation status.
- Patients must have had palpable splenomegaly that is equal to or greater than 5 cm below the left costal margin.
- Patients must have had hemoglobin less than 10 g/dL
Key exclusion criteria (29 listed)
- Patients who had prior treatment with any JAK1 or JAK2 inhibitor.
- Patients who had known hypersensitivity to ruxolitinib or other JAK1/JAK2 inhibitors, or to their excipients.
- Patients who had been eligible for hematopoietic stem cell transplantation (suitable candidate and a suitable donor is available).
- Patients who had inadequate bone marrow reserve at baseline as demonstrated by at least one of the following:
- Patients who had severely impaired renal function defined by: Creatinine clearance less than 30 mL/min.
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 |
|---|---|---|
| ruxolitinibRuxolitinib was supplied in 5 mg tablets to be taken orally approximately 12 hours apart (morning and night) | Drug | All Subjects |
Primary outcome
Percentage of Participants With at Least 50% Reduction in Spleen Length From Baseline at Week 24
Time frame: Baseline up to week 24
Percentage of participants achieving a 50% reduction in spleen length at week 24. For subjects with palpable spleen at baseline and non-palpable at post-baseline, the post-baseline spleen are imputed as 0. Subjects who had palpable, but missing spleen length at baseline is excluded from the analysis. Subjects with missing spleen length at Week 24 or who withdraw earlier from the study are considered as a non-responder. The 95% CI is computed using exact Clopper-Pearson method.
5 secondary outcomes
Percentage of Participants With at Least 50% Reduction in Spleen Length From Baseline at Week 48
Time frame: Baseline up to week 48
Percentage of Participants by Spleen Length Reduction or no Increase From Baseline Category at Week 24 and Week 48
Time frame: baseline, weeks 24 and 48
Percentage of Participants With at Least a 50% Reduction in Myelofibrosis 7 Item Symptom Scale (MF-7) and Myelofibrosis Symptom Assessment Form (MFSAF) at Week 24
Time frame: Baseline and week 24
Patient Global Impression of Change (PGIC) at Week 24 and Week 48
Time frame: Baseline up to week 48
Percentage of Participants Transfusion Independency From Baseline up to Week 96
Time frame: Baseline up to week 96
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Apr 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
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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.
The record lists no contact. Use the official record to reach the sponsor.
20 sites in 11 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ruxolitinib in people with Primary Myelofibrosis and Post-Polycythemia Vera-Myelofibrosis, run by Novartis Pharmaceuticals at 20 sites in 11 countries.
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 9 inclusion and 29 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 30 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 20 sites in Italy, Russia, Spain, Belgium, Bulgaria and 6 more countries. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 30 Apr 2020). 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 at Least 50% Reduction in Spleen Length From Baseline at Week 24 (time frame: Baseline up to week 24). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 30 Apr 2020.