MPN (Myeloproliferative Neoplasms) Clinical Trial
Official title:
A Randomized, Double-blind, Placebo-controlled Study of the JAK Inhibitor INCB018424 Tablets Administered Orally to Subjects With Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis or Post-Essential Thrombocythemia Myelofibrosis
Verified date | February 2018 |
Source | Incyte Corporation |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
This was a randomized, double-blind study comparing the efficacy and safety of ruxolitinib (INCB018424) tablets to matching placebo tablets in patients diagnosed with Myelofibrosis (either Primary Myelofibrosis (PMF) or Post-Polycythemia Vera Myelofibrosis (PPV-MF) or Post-Essential Thrombocythemia Myelofibrosis (PET-MF).
Status | Completed |
Enrollment | 309 |
Est. completion date | October 2015 |
Est. primary completion date | November 2010 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility |
Inclusion Criteria: - Subjects must be diagnosed with primary myelofibrosis (PMF), post-polycythemia vera-myelofibrosis (PPV-MF) or post-essential thrombocythemia-myelofibrosis (PET-MF) according to the 2008 World Health Organization criteria - Subjects with myelofibrosis 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 Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, 2 or 3 - Subjects who have not previously received treatment with a Janus kinase (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 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 |
Country | Name | City | State |
---|---|---|---|
n/a |
Lead Sponsor | Collaborator |
---|---|
Incyte Corporation |
United States, Australia, Canada,
Verstovsek S, Mesa R, Gotlib J, et al. Results of COMFORT-I, a randomized double-blind phase III trial of JAK1/2 inhibitor INCB18424 (424) vs placebo (PB) for patients with myelofibrosis (MF). The 47th Annual ASCO meeting, Chicago, IL. J Clin Oncol 2011; 29 (suppl; abstract 6500). Verstovsek S, Mesa R, Gotlib J, et al. Results of COMFORT-I, a randomized, double-blind phase III trial of the JAK1 and JAK2 inhibitor ruxolitinib (INCB018424) versus placebo for patients with myelofibrosis. The 16th Annual EHA meeting, London, UK. Haematologica 2011; 96 (suppl 2; abstract 0505).
Verstovsek S, Mesa RA, Gotlib J, Levy RS, Gupta V, DiPersio JF, Catalano JV, Deininger M, Miller C, Silver RT, Talpaz M, Winton EF, Harvey JH Jr, Arcasoy MO, Hexner E, Lyons RM, Paquette R, Raza A, Vaddi K, Erickson-Viitanen S, Koumenis IL, Sun W, Sandor — View Citation
Verstovsek S, Mesa RA, Gotlib J, Levy RS, Gupta V, DiPersio JF, Catalano JV, Deininger MW, Miller CB, Silver RT, Talpaz M, Winton EF, Harvey JH Jr, Arcasoy MO, Hexner EO, Lyons RM, Paquette R, Raza A, Vaddi K, Erickson-Viitanen S, Sun W, Sandor V, Kantarj — View Citation
Verstovsek S, Mesa RA, Gotlib J, Levy RS, Gupta V, DiPersio JF, Catalano JV, Deininger MW, Miller CB, Silver RT, Talpaz M, Winton EF, Harvey JH Jr, Arcasoy MO, Hexner EO, Lyons RM, Raza A, Vaddi K, Sun W, Peng W, Sandor V, Kantarjian H; COMFORT-I investig — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Number of Participants Achieving = 35% Reduction in Spleen Volume From Baseline to Week 24 | Spleen volume was assessed by magnetic resonance imaging (MRI) or by computed tomography (CT) scans if MRI was not suitable, and analyzed by a blinded central laboratory reader. Patients who withdrew, crossed over to ruxolitinib prior to the visit, or had a missing value at the visit were considered non-responders. | Baseline and Week 24 | |
Secondary | Maintenance of a = 35% Reduction From Baseline in Spleen Volume Among Patients Initially Randomized to Receive Ruxolitinib | The maintenance of = 35% reduction from Baseline in spleen volume was assessed up until the data cutoff date using the Kaplan-Meier method for patients who had at least one measured = 35% reduction, and who either had at least one subsequent measurement or who subsequently dropped out prior to another assessment. | Baseline Visit and every 12 weeks until the data cut-off date (up to 14 months). | |
Secondary | Duration of Maintenance of a = 35% Reduction From Baseline in Spleen Volume Among Patients Initially Randomized to Receive Ruxolitinib | The duration of = 35% reduction from Baseline in spleen volume was defined as the longest duration of consecutive measurements of = 35% reduction observed before the data cut-off date for patients who had at least one measured = 35% reduction, and who either had at least one subsequent measurement or, who subsequently dropped out prior to another assessment. The duration of a = 35% reduction from Baseline in spleen volume was analyzed using the Kaplan-Meier method. | Baseline Visit and every 12 weeks until the data cut-off date (up to 14 months). | |
Secondary | Number of Participants With a = 50% Reduction in Total Symptom Score From Baseline to Week 24 | Symptoms of myelofibrosis were assessed using a modified Myelofibrosis Symptom Assessment Form (MFSAF) Version 2.0 diary. Using the diary, patients rated the following symptoms on a scale from 0 (absent) to 10 (worst imaginable): night sweats, itching, abdominal discomfort, pain under ribs on left, feeling of fullness (early satiety), and muscle/bone pain. The total symptom score ranged from 0-60 and was calculated as the sum of the 6 symptom scores. A higher score indicates worse symptoms. | Baseline and Week 24. Baseline total score was the average of the daily total scores for the last 7 days prior to randomization. The Week 24 total score was the average of daily total scores from the 28 days prior to the Week 24 visit. | |
Secondary | Change From Baseline to Week 24 in Total Symptom Score | Symptoms of myelofibrosis were assessed using a modified Myelofibrosis Symptom Assessment Form (MFSAF) Version 2.0 diary. Using the diary, patients rated the following symptoms on a scale from 0 (absent) to 10 (worst imaginable): night sweats, itching, abdominal discomfort, pain under ribs on left, feeling of fullness (early satiety), and muscle/bone pain. The total symptom score ranged from 0-60 and was calculated as the sum of the 6 symptom scores. A higher score indicates worse symptoms hence a negative change from baseline indicates improvement. | Baseline and Week 24. Baseline total score was the average of the daily total scores for the last 7 days prior to randomization. The Week 24 total score was the average of daily total scores from the 28 days prior to the Week 24 visit. | |
Secondary | Overall Survival | Overall survival is reported here by the number of deaths from randomization until the data cut-off. Patients were censored at the time of database cut-off or the later of either the date of withdrawal or the date of last follow-up for patients who withdrew from study before the date of data cut. The survival time was analyzed using the Kaplan-Meier method. | From randomization to the data cut-off date (up to 14 months). | |
Secondary | Overall Survival Time | Overall survival was assessed by the time to death or censoring. Patients were censored at the time of database cut-off or the later of either the date of withdrawal or the date of last follow-up for patients who withdrew from study before the date of data cut. The survival time was analyzed using the Kaplan-Meier method. | From randomization to the data cut-off date (up to 14 months). | |
Secondary | Overall Survival - Extended Data | Overall survival is reported here by the number of deaths from randomization until 01 March 2011. Patients were censored at this time or the later of either the date of withdrawal or the date of last follow-up for patients who withdrew from study before the date of data cut. The survival time was analyzed using the Kaplan-Meier method. This outcome reports data from August 2009 through March 2011 to coincide with a pre-planned New Drug Application (NDA) 120-day safety update. | From randomization to 4 months after the data cut-off date (up to 18 months). | |
Secondary | Overall Survival Time - Extended Data | Overall survival was assessed by the time to death or censoring up until 01 March 2011. Patients were censored at this time or the later of either the date of withdrawal or the date of last follow-up for patients who withdrew from study before the date of data cut. The survival time was analyzed using the Kaplan-Meier method. This outcome reports data from August 2009 through March 2011 to coincide with a pre-planned New Drug Application (NDA) 120-day safety update. | From randomization to 4 months after the data cut-off date (up to 18 months). | |
Secondary | Overall Survival at Week 144 | Overall survival is reported here by the number of deaths from randomization until the data cut-off. Patients were censored at the time of database cut-off or the later of either the date of withdrawal or the date of last follow-up for patients who withdrew from study before the date of database cut-off. The survival time was analyzed using the Kaplan-Meier method. | Week 144 | |
Secondary | Overall Survival Time at Week 144 | Overall survival was assessed by the time to death or censoring. Patients were censored at the time of database cut-off or the later of either the date of withdrawal or the date of last follow-up for patients who withdrew from study before the date of database cut-off. The survival time was analyzed using the Kaplan-Meier method. | Week 144 |
Status | Clinical Trial | Phase | |
---|---|---|---|
Terminated |
NCT03123588 -
Phase 2 Study of Ruxolitinib Versus Anagrelide in Subjects With Essential Thrombocythemia Who Are Resistant to or Intolerant of Hydroxyurea (RESET-272)
|
Phase 2 | |
Completed |
NCT01348490 -
Ruxolitinib (INCB018424) in Participants With Primary Myelofibrosis (PMF), Post Essential Thrombocythemia-myelofibrosis and Post Polycythemia Vera-myelofibrosis (PPV-MF)
|
Phase 2 | |
Completed |
NCT02252159 -
Prospective Observational Study Of Patients With Polycythemia Vera In US Clinical Practices (REVEAL)
|
||
Completed |
NCT01633372 -
An Open Label Study of Itacitinib Administered Orally in Patients With Myelofibrosis
|
Phase 2 | |
Completed |
NCT03144687 -
A Study of Itacitinib in Combination With Low-Dose Ruxolitinib or Itacitinib Alone Following Ruxolitinib in Participants With Myelofibrosis
|
Phase 2 | |
Terminated |
NCT02718300 -
A Study of INCB050465 in Combination With Ruxolitinib in Subjects With Myelofibrosis
|
Phase 2 | |
Completed |
NCT02953704 -
Myelofibrosis and Essential Thrombocythemia Observational Study (MOST)
|
||
Active, not recruiting |
NCT03011372 -
A Study to Evaluate the Efficacy and Safety of Pemigatinib (INCB054828) in Subjects With Myeloid/Lymphoid Neoplasms With FGFR1 Rearrangement - (FIGHT-203)
|
Phase 2 |