Controlled Myelofibrosis Study With Oral Janus-associated Kinase (JAK) Inhibitor Treatment-II: The COMFORT-II Trial
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT00934544 |
Recruitment Status :
Completed
First Posted : July 8, 2009
Results First Posted : May 30, 2012
Last Update Posted : August 19, 2019
|
- Study Details
- Tabular View
- Study Results
- Disclaimer
- How to Read a Study Record
Condition or disease | Intervention/treatment | Phase |
---|---|---|
Myelofibrosis | Drug: Ruxolitinib Drug: Best Available Therapy (BAT) | Phase 3 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 219 participants |
Allocation: | Randomized |
Intervention Model: | Crossover Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | A Randomized Study of Ruxolitinib Tablets Compared to Best Available Therapy in Subjects With Primary Myelofibrosis, Post-Polycythemia Vera-Myelofibrosis or Post-Essential Thrombocythemia Myelofibrosis |
Actual Study Start Date : | July 1, 2009 |
Actual Primary Completion Date : | March 4, 2015 |
Actual Study Completion Date : | March 4, 2015 |
Arm | Intervention/treatment |
---|---|
Experimental: Ruxolitinib
5 mg tablets administered orally in an outpatient setting according to the protocol-specified dosing schedule
|
Drug: Ruxolitinib
5 mg tablets packaged as 60-count in high-density polyethylene bottles |
Active Comparator: Best Available Therapy (BAT)
Commercially available therapy, oral or parenteral, per manufacturer's instructions and Investigator discretion. BAT included the option of no treatment. Patients randomized to BAT were eligible to cross over to receive open-label ruxolitinib after a qualifying progression event, if they met the safety criteria. After the primary analysis in January 2011, patients randomized to receive BAT were allowed to cross over to receive ruxolitinib and move to the extension phase of the study without a qualifying progression event. |
Drug: Best Available Therapy (BAT)
Prescribing and usage per respective package inserts |
- Percentage of Participants With at Least 35% Reduction in Spleen Volume From Baseline at Week 48 [ Time Frame: Baseline, 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.
- Duration of Maintenance of Spleen Volume Reduction (Median) [ Time Frame: Baseline, up to Year 5 ]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.
- Duration of Maintenance of Spleen Volume Reduction (Kaplan-Meier Estimates) [ Time Frame: Baseline, up to Year 5 ]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.
- Percentage of Participants With at Least 35% Reduction in Spleen Volume From Baseline at Week 24 [ Time Frame: Baseline, 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.
- Time to First at Least 35% Reduction in Spleen Volume From Baseline by Treatment (Primary Analysis) [ Time Frame: Time from randomization and date of the first MRI showing at least 35% reduction from baseline in spleen volume ]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
- Progression-free Survival (PFS) [ Time Frame: Time from randomization and the earliest of either increase in spleen volume >=25% from on-study nadir, splenic irradiation, splenectomy, leukemic transformation or death ]Median of time progression free survival (95% CI), years
- Leukemia-free Survival (LFS) [ Time Frame: Time from randomization and earliest of either leukemia or death ]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
- Overall Survival (OS) [ Time Frame: From randomization until death from any cause ]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
- Percentage of Participants With Bone Marrow Histomorphology at Week 48 (Primary Analysis) [ Time Frame: 48 weeks ]
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
- Bone Marrow Histomorphology [ Time Frame: Baseline, once a year ]
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
- Duration of Follow-up by Treatment [ Time Frame: baseline, 260 weeks (end of study) ]Number of Participants with duration of Follow up
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00934544
Study Director: | Novartis Pharmaceuticals | Novartis Pharmaceuticals |
Responsible Party: | Novartis Pharmaceuticals |
ClinicalTrials.gov Identifier: | NCT00934544 |
Other Study ID Numbers: |
CINC424A2352 CINCB 18424-352 ( Other Identifier: INCYTE ) 2009-009858-24 ( EudraCT Number ) |
First Posted: | July 8, 2009 Key Record Dates |
Results First Posted: | May 30, 2012 |
Last Update Posted: | August 19, 2019 |
Last Verified: | July 2019 |
Studies a U.S. FDA-regulated Drug Product: | No |
Myelofibrosis Post-Polycythemia Vera Myelofibrosis Post-Essential Thrombocythemia Myelofibrosis |
Polycythemia Vera Primary Myelofibrosis Myeloproliferative Disorders Bone Marrow Diseases Hematologic Diseases |
Bone Marrow Neoplasms Hematologic Neoplasms Neoplasms by Site Neoplasms |