TriangleNCT00934544 · CITED IN SOURCE DOCUMENTS
Controlled Myelofibrosis Study With Oral Janus-associated Kinase (JAK) Inhibitor Treatment-II: The COMFORT-II Trial
An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.
- Phase
- PHASE3
- Status at capture
- COMPLETED
- Registry last update
- 2019-08-19
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).
Open the original ClinicalTrials.gov record → · Download preserved record
What did the study report?
Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.
Participant flow
Baseline characteristics
Percentage of Participants With at Least 35% Reduction in Spleen Volume From Baseline at Week 48
Duration of Maintenance of Spleen Volume Reduction (Median)
Duration of Maintenance of Spleen Volume Reduction (Kaplan-Meier Estimates)
Percentage of Participants With at Least 35% Reduction in Spleen Volume From Baseline at Week 24
Time to First at Least 35% Reduction in Spleen Volume From Baseline by Treatment (Primary Analysis)
Progression-free Survival (PFS)
Leukemia-free Survival (LFS)
Overall Survival (OS)
Percentage of Participants With Bone Marrow Histomorphology at Week 48 (Primary Analysis)
Bone Marrow Histomorphology
Duration of Follow-up by Treatment
Adverse events
Limitations, agreements, and source contact
Who could take part
- eligibility Criteria
- 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
- healthy Volunteers
- false
- minimum Age
- 18 Years
- sex
- ALL
- std Ages
- ADULT
- OLDER_ADULT
Treatment arms and interventions
- arm Groups
- description
- 5 mg tablets administered orally in an outpatient setting according to the protocol-specified dosing schedule
- intervention Names
- Drug: Ruxolitinib
- label
- Ruxolitinib
- type
- EXPERIMENTAL
- description
- 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.
- intervention Names
- Drug: Best Available Therapy (BAT)
- label
- Best Available Therapy (BAT)
- type
- ACTIVE_COMPARATOR
- interventions
- arm Group Labels
- Ruxolitinib
- description
- 5 mg tablets packaged as 60-count in high-density polyethylene bottles
- name
- Ruxolitinib
- type
- DRUG
- arm Group Labels
- Best Available Therapy (BAT)
- description
- Prescribing and usage per respective package inserts
- name
- Best Available Therapy (BAT)
- type
- DRUG
Study design
- allocation
- RANDOMIZED
- intervention Model
- CROSSOVER
- masking Info
- masking
- NONE
- primary Purpose
- TREATMENT
Enrollment
- count
- 219
- type
- ACTUAL
Registered outcome plans (not posted results)
- primary Outcomes
- description
- 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.
- measure
- Percentage of Participants With at Least 35% Reduction in Spleen Volume From Baseline at Week 48
- time Frame
- Baseline, Week 48
- secondary Outcomes
- description
- 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.
- measure
- Duration of Maintenance of Spleen Volume Reduction (Median)
- time Frame
- Baseline, up to Year 5
- description
- 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.
- measure
- Duration of Maintenance of Spleen Volume Reduction (Kaplan-Meier Estimates)
- time Frame
- Baseline, up to Year 5
- description
- 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.
- measure
- Percentage of Participants With at Least 35% Reduction in Spleen Volume From Baseline at Week 24
- time Frame
- Baseline, Week 24
- description
- 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
- measure
- 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
- description
- Median of time progression free survival (95% CI), years
- measure
- 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
- description
- 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
- measure
- Leukemia-free Survival (LFS)
- time Frame
- Time from randomization and earliest of either leukemia or death
- description
- 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
- measure
- Overall Survival (OS)
- time Frame
- From randomization until death from any cause
- description
- 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
- measure
- Percentage of Participants With Bone Marrow Histomorphology at Week 48 (Primary Analysis)
- time Frame
- 48 weeks
- description
- 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
- measure
- Bone Marrow Histomorphology
- time Frame
- Baseline, once a year
- description
- Number of Participants with duration of Follow up
- measure
- Duration of Follow-up by Treatment
- time Frame
- baseline, 260 weeks (end of study)
Full study description
- brief 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).
- detailed 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.
Source references
- references
- citation
- Verstovsek S, Gotlib J, Mesa RA, Vannucchi AM, Kiladjian JJ, Cervantes F, Harrison CN, Paquette R, Sun W, Naim A, Langmuir P, Dong T, Gopalakrishna P, Gupta V. Long-term survival in patients treated with ruxolitinib for myelofibrosis: COMFORT-I and -II pooled analyses. J Hematol Oncol. 2017 Sep 29;10(1):156. doi: 10.1186/s13045-017-0527-7.
- pmid
- 28962635
- type
- DERIVED
- citation
- McMullin MF, Harrison CN, Niederwieser D, Demuynck H, Jakel N, Gopalakrishna P, McQuitty M, Stalbovskaya V, Recher C, Theunissen K, Gisslinger H, Kiladjian JJ, Al-Ali HK. The use of erythropoiesis-stimulating agents with ruxolitinib in patients with myelofibrosis in COMFORT-II: an open-label, phase 3 study assessing efficacy and safety of ruxolitinib versus best available therapy in the treatment of myelofibrosis. Exp Hematol Oncol. 2015 Sep 15;4:26. doi: 10.1186/s40164-015-0021-2. eCollection 2015.
- pmid
- 26380150
- type
- DERIVED
- citation
- Vannucchi AM, Kantarjian HM, Kiladjian JJ, Gotlib J, Cervantes F, Mesa RA, Sarlis NJ, Peng W, Sandor V, Gopalakrishna P, Hmissi A, Stalbovskaya V, Gupta V, Harrison C, Verstovsek S; COMFORT Investigators. A pooled analysis of overall survival in COMFORT-I and COMFORT-II, 2 randomized phase III trials of ruxolitinib for the treatment of myelofibrosis. Haematologica. 2015 Sep;100(9):1139-45. doi: 10.3324/haematol.2014.119545. Epub 2015 Jun 11.
- pmid
- 26069290
- type
- DERIVED
- citation
- Cervantes F, Vannucchi AM, Kiladjian JJ, Al-Ali HK, Sirulnik A, Stalbovskaya V, McQuitty M, Hunter DS, Levy RS, Passamonti F, Barbui T, Barosi G, Harrison CN, Knoops L, Gisslinger H; COMFORT-II investigators. Three-year efficacy, safety, and survival findings from COMFORT-II, a phase 3 study comparing ruxolitinib with best available therapy for myelofibrosis. Blood. 2013 Dec 12;122(25):4047-53. doi: 10.1182/blood-2013-02-485888. Epub 2013 Oct 30.
- pmid
- 24174625
- type
- DERIVED
- citation
- Wilkins BS, Radia D, Woodley C, Farhi SE, Keohane C, Harrison CN. Resolution of bone marrow fibrosis in a patient receiving JAK1/JAK2 inhibitor treatment with ruxolitinib. Haematologica. 2013 Dec;98(12):1872-6. doi: 10.3324/haematol.2013.095109. Epub 2013 Sep 20.
- pmid
- 24056820
- type
- DERIVED
- citation
- Mesa RA, Kiladjian JJ, Verstovsek S, Al-Ali HK, Gotlib J, Gisslinger H, Levy R, Siulnik A, Gupta V, Khan M, DiPersio JF, McQuitty M, Catalano JV, Hunter DS, Knoops L, Deininger M, Cervantes F, Miller C, Vannucchi AM, Silver RT, Barbui T, Talpaz M, Barosi G, Winton EF, Mendeson E, Harvey JH Jr, Arcasoy MO, Hexner E, Lyons RM, Paquette R, Raza A, Sun W, Sandor V, Kantarjian HM, Harrison C. Comparison of placebo and best available therapy for the treatment of myelofibrosis in the phase 3 COMFORT studies. Haematologica. 2014 Feb;99(2):292-8. doi: 10.3324/haematol.2013.087650. Epub 2013 Aug 2.
- pmid
- 23911705
- type
- DERIVED
- citation
- Harrison C, Kiladjian JJ, Al-Ali HK, Gisslinger H, Waltzman R, Stalbovskaya V, McQuitty M, Hunter DS, Levy R, Knoops L, Cervantes F, Vannucchi AM, Barbui T, Barosi G. JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis. N Engl J Med. 2012 Mar 1;366(9):787-98. doi: 10.1056/NEJMoa1110556.
- pmid
- 22375970
- type
- DERIVED
Source notices and limitations
Discovery and provenance
- release id
- ctgov-registry-7ad944f6deaf1f5cd6122126
- edge id
- nct-edge-593e9207d1e26f72e1b0
- requested nct id
- NCT00934544
- primary nct id
- NCT00934544
- source kind
- nci_explicit_reference_or_link
- source record id
- Source null
- source file sha256
- 5d67acd07af1c8c398ca5fc68cf908fbd85fe3fe5708f4d51270231c1dd2f93e
- payload sha256
- 8f83b560e9ce12a8c33f3166be3d0cfa32ac62823805f0c4283924756fee14da
- payload
- clinical indication matching status
- not_inferred
- end exclusive
- true
- id
- nct-edge-593e9207d1e26f72e1b0
- link basis
- explicit_NCT_identifier_in_acquired_source
- nct id
- NCT00934544
- occurrences
- context exact
- ed to ruxolitinib or to either placebo (<a href="/clinicaltrials/NCT00952289">COMFORT-I</a> [NCT00952289]) or best-available therapy (<a href="/clinicaltrials/NCT00934544">COMFORT-II</a> [NCT00934544]).[<a href="#cit/section_5.37">37</a>,<a href="#cit/section_5.38">38</a>]<div class="pdq-content-list"><ul id="_476"><li>At 48 wee
- end
- 97598
- exact text
- NCT00934544
- start
- 97587
- context exact
- r placebo (<a href="/clinicaltrials/NCT00952289">COMFORT-I</a> [NCT00952289]) or best-available therapy (<a href="/clinicaltrials/NCT00934544">COMFORT-II</a> [NCT00934544]).[<a href="#cit/section_5.37">37</a>,<a href="#cit/section_5.38">38</a>]<div class="pdq-content-list"><ul id="_476"><li>At 48 weeks, patients who received rux
- end
- 97627
- exact text
- NCT00934544
- start
- 97616
- offset unit
- unicode_code_points
- source file
- /tmp/cancer-full-research/nci/raw/386d32d532a5041e68.html
- source file sha256
- 5d67acd07af1c8c398ca5fc68cf908fbd85fe3fe5708f4d51270231c1dd2f93e
- source json pointer
- Source null
- source kind
- nci_explicit_reference_or_link
- source record id
- Source null
- source retrieved at
- 2026-09-09T23:22:08.366806+00:00
- source string basis
- UTF-8_text_with_universal_newline_translation
- source string sha256
- 04fd1210e35e69a6987a4d0936de42da25c4659d300c8be83cd5fb6547471174
- source title
- Myeloproliferative Neoplasms Treatment (PDQ®)–Health Professional Version
- source update dates
- context
- Updated: September 27, 2024
- datetime
- 2024-09-27T12:00:00Z
- display
- September 27, 2024
- release id
- ctgov-registry-7ad944f6deaf1f5cd6122126
- edge id
- nct-edge-c9c9af135b3729a1a106
- requested nct id
- NCT00934544
- primary nct id
- NCT00934544
- source kind
- fda_spl_label
- source record id
- 1c261eb0-f426-47a1-8281-62282d207644
- source file sha256
- 0dba7a040bbbf460aa9f482c5b67c9f28f75fc9df775ee1e7b345b758f780e07
- payload sha256
- 321c44e074fb612b12faea400641b635aadb86e4177aa93c51e7bd7a76866c36
- payload
- application numbers
- NDA202192
- NDA217180
- clinical indication matching status
- not_inferred
- end exclusive
- true
- id
- nct-edge-c9c9af135b3729a1a106
- link basis
- explicit_NCT_identifier_in_acquired_source
- nct id
- NCT00934544
- occurrences
- context exact
- eduction in Total Symptom Score from baseline to Week 24 as measured by the modified Myelofibrosis Symptom Assessment Form (MFSAF) v2.0 diary. Study 2 Study 2 (NCT00934544) was an open-label, randomized study in 219 patients. Patients were randomized 2:1 to JAKAFI versus BAT. Best available therapy was selected by the investigato
- end
- 2960
- exact text
- NCT00934544
- start
- 2949
- offset unit
- unicode_code_points
- source file
- /tmp/cancer-full-research/indications/raw/labels-00000.json
- source file sha256
- 0dba7a040bbbf460aa9f482c5b67c9f28f75fc9df775ee1e7b345b758f780e07
- source json pointer
- /results/95/clinical_studies/0
- source kind
- fda_spl_label
- source record id
- 1c261eb0-f426-47a1-8281-62282d207644
- source string basis
- parsed_JSON_string_unmodified
- source string sha256
- c85c2b4e39e4f2ccc225800493c71369808ab267bb645d8a9ad0133c4aa2f8a4
- spl effective time
- 20260720
- spl set id
- f1c82580-87ae-11e0-bc84-0002a5d5c51b
Preserved source evidence · Not medical advice