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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT00934544
Other study ID # CINC424A2352
Secondary ID CINCB 18424-3522
Status Completed
Phase Phase 3
First received
Last updated
Start date July 1, 2009
Est. completion date March 4, 2015

Study information

Verified date July 2019
Source Novartis
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This was an open label, randomized study comparing the efficacy and safety of randomized 2:1 Ruxolitinib tablets versus best-available therapy, as selected by the investigator. The purpose was to compare the efficacy, safety and tolerability of Ruxolitinib (INC424/INCB018424) given twice daily to the best-available therapy, in subjects with primary myelofibrosis (PMF), post polycythemia vera myelofibrosis (PPV-MF) or post essential thrombocythemia myelofibrosis (PET-MF).


Description:

This study included a randomized treatment phase, followed by an extension phase. The treatment phase lasted from Study Day 1 (day of randomization) to the occurrence of a protocol-specified progressive disease event or study conclusion, whichever came first. The extension phase (including crossover of control group patients) lasted from the progressive disease event until the earliest of the following events: a) the patient was no longer receiving clinical benefit, b) the patient chose to withdraw from the study, or c) the study ended. All patients received ruxolitinib in the extension phase of the study. Maximum individual patient duration was 5 years.


Recruitment information / eligibility

Status Completed
Enrollment 219
Est. completion date March 4, 2015
Est. primary completion date March 4, 2015
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria:

- Subjects must be diagnosed with PMF, PPV-MF or PET-MF according to the 2008 World Health Organization criteria

- Subjects with MF requiring therapy must be classified as high risk OR intermediate risk level 2 according to the prognostic factors defined by the International Working Group

- Subjects with an ECOG performance status of 0, 1, 2 or 3

- Subjects with peripheral blood blast count of < 10%.

- Subjects who have not previously received treatment with a JAK inhibitor

Exclusion Criteria:

- Subjects with a life expectancy of less than 6 months

- Subjects with inadequate bone marrow reserve as demonstrated by specific clinical laboratory counts

- Subjects 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

- Subjects with inadequate liver or renal function

- Subjects with clinically significant bacterial, fungal, parasitic or viral infection which require therapy

- Subjects with an active malignancy over the previous 5 years except specific skin cancers

- Subjects with severe cardiac conditions

- Subjects who have had splenic irradiation within 12 months

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Ruxolitinib
5 mg tablets packaged as 60-count in high-density polyethylene bottles
Best Available Therapy (BAT)
Prescribing and usage per respective package inserts

Locations

Country Name City State
Austria Novartis Investigative Site Innsbruck
Austria Novartis Investigative Site Linz
Austria Novartis Investigative Site Salzburg
Austria Novartis Investigative Site Vienna
Belgium Novartis Investigative Site Antwerp
Belgium Novartis Investigative Site Antwerp
Belgium Novartis Investigative Site Brugge
Belgium Novartis Investigative Site Brussel
Belgium Novartis Investigative Site Hasselt
Belgium Novartis Investigative Site Kortrijk
Belgium Novartis Investigative Site La Louvière
Belgium Novartis Investigative Site Leuven
Belgium Novartis Investigative Site Roeselare
Belgium Novartis Investigative Site Yvoir
France Novartis Investigative Site Amiens cedex 1
France Novartis Investigative Site Caen Cedex
France Novartis Investigative Site Grenoble
France Novartis Investigative Site Lens Cedex
France Novartis Investigative Site Lille
France Novartis Investigative Site Lyon
France Novartis Investigative Site Marseille
France Novartis Investigative Site Nimes
France Novartis Investigative Site Paris
France Novartis Investigative Site Paris
France Novartis Investigative Site Paris
France Novartis Investigative Site Pessac
France Novartis Investigative Site Poitiers Cedex
France Novartis Investigative Site Rennes
France Novartis Investigative Site Strasbourg
France Novartis Investigative Site Toulouse Cedex
France Novartis Investigative Site Villejuif Cedex
Germany Novartis Investigative Site Berlin
Germany Novartis Investigative Site Frankfurt/M
Germany Novartis Investigative Site Köln
Germany Novartis Investigative Site Magdeburg
Germany Novartis Investigative Site Mainz
Germany Novartis Investigative Site Muenster
Germany Novartis Investigative Site Stuttgart
Germany Novartis Investigative Site Tuebingen
Germany Novartis Investigative Site Ulm
Italy Novartis Investigative Site Florence
Italy Novartis Investigative Site Milano MI
Italy Novartis Investigative Site Monza MB
Italy Novartis Investigative Site Orbassano
Italy Novartis Investigative Site Pavia
Italy Novartis Investigative Site Pavia (pv)
Netherlands Novartis Investigative Site Amsterdam
Netherlands Novartis Investigative Site Den Haag
Netherlands Novartis Investigative Site Groningen
Netherlands Novartis Investigative Site Maastricht
Netherlands Novartis Investigative Site Nijmegen
Netherlands Novartis Investigative Site Rotterdam
Spain Novartis Investigative Site Barcelona Catalunya
Spain Novartis Investigative Site Majadahonda Madrid
Spain Novartis Investigative Site Valencia Comunidad Valenciana
Sweden Novartis Investigative Site Göteborg
Sweden Novartis Investigative Site Stockholm
United Kingdom Novartis Investigative Site Belfast
United Kingdom Novartis Investigative Site Cambridge
United Kingdom Novartis Investigative Site London
United Kingdom Novartis Investigative Site Oxford

Sponsors (1)

Lead Sponsor Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

Austria,  Belgium,  France,  Germany,  Italy,  Netherlands,  Spain,  Sweden,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Primary Percentage of Participants With at Least 35% Reduction in Spleen Volume From Baseline at Week 48 The change in spleen volume from baseline to week 48 was measured by magnetic resonance imaging (MRI) (or by computer tomography (CT) for participants unable to undergo MRI) and was calculated only for participants who had an evaluable spleen volume at baseline. The percentage of participants achieving a greater than or equal to 35% reduction in spleen volume from baseline to week 48 was then calculated by treatment group. Baseline, Week 48
Secondary Duration of Maintenance of Spleen Volume Reduction (Median) DoMSR is defined as the interval between the first spleen volume measurement that is >=35% reduction from baseline and the first scan that is no longer = 35% reduction AND that is a >25% increase over nadir. It was evaluated using the Kaplan-Meier estimate for each treatment arm. The analysis was performed only for subjects who achieved greater than 35% reduction in spleen volume. Baseline, up to Year 5
Secondary Duration of Maintenance of Spleen Volume Reduction (Kaplan-Meier Estimates) ?This is defined as the interval between randomization and date of the first MRI showing a 35% reduction from baseline in spleen volume. The analysis was performed for participants who achieved a 35% reduction in spleen volume. Baseline, up to Year 5
Secondary Percentage of Participants With at Least 35% Reduction in Spleen Volume From Baseline at Week 24 The change in spleen volume from baseline to week 24 was measured by magnetic resonance imaging (MRI) (or by computer tomography (CT) for participants unable to undergo MRI) and was calculated only for participants who had an evaluable spleen volume at baseline. The percentage of participants achieving a greater than or equal to 35% reduction in spleen volume from baseline to week 24 was then calculated by treatment group. Baseline, Week 24
Secondary Time to First at Least 35% Reduction in Spleen Volume From Baseline by Treatment (Primary Analysis) This is defined as the interval between randomization and date of the first MRI showing at least 35% reduction from baseline in spleen volume. The analysis was performed for participants who achieved a 35% reduction in spleen volume Time from randomization and date of the first MRI showing at least 35% reduction from baseline in spleen volume
Secondary Progression-free Survival (PFS) Median of time progression free survival (95% CI), years Time from randomization and the earliest of either increase in spleen volume >=25% from on-study nadir, splenic irradiation, splenectomy, leukemic transformation or death
Secondary Leukemia-free Survival (LFS) Time from randomization and earliest of either (1) date of bone marrow blast count of 20% or greater; (2) date of first peripheral blast count of 20% or greater that was subsequently confirmed to sustain for at least 8 weeks; (3) date of death from any cause Time from randomization and earliest of either leukemia or death
Secondary Overall Survival (OS) Defined as the interval between randomization and the date of the bone marrow blast count of 20% or greater OR the date of the first peripheral blast count of 20% or greater that was subsequently confirmed to have been sustained for at least 8 weeks OR the date of death from any cause, whichever occurs first. OS was summarized using Kaplan-Meier estimates for each treatment arm. The estimates were supplemented by tables of number of events and probability estimates at several timepoints From randomization until death from any cause
Secondary Percentage of Participants With Bone Marrow Histomorphology at Week 48 (Primary Analysis) This was noted as fibrosis density and was tabulated by fibrosis grade at baseline and at week 48 (post-baseline). Descriptive statistics (participant percentages) were used.
Fibrosis grades: 0 Scattered linear reticulin with no intersections corresponding to normal bone marrow ; 1 Loose network of reticulin with many intersections, especially in perivascular areas; 2 Diffuse and dense increase in reticulin with extensive intersections, occasionally with only focal bundles of collagen and/or focal osteosclerosis; 3 Diffuse and dense increase in reticulin with extensive intersections with coarse bundles of collagen, often associated with significant osteosclerosis
48 weeks
Secondary Bone Marrow Histomorphology Shift table from baseline to last available postbaseline fibrosis grade by treatment
The grade gives an indication of the activity or amount of inflammation and the stage represents the amount of fibrosis or scarring. The grade is assigned a number based on the degree of inflammation, which is usually scored from 0-4 with 0 being no activity and 3 or 4 considered severe activity
Baseline, once a year
Secondary Duration of Follow-up by Treatment Number of Participants with duration of Follow up baseline, 260 weeks (end of study)
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