Myelofibrosis; AnemiaRuxo-EPONCT03208803
Combination of JAK2 Inhibitor and Erythropoiesis-stimulating Agent in Myelofibrosis
An observational study of Myelofibrosis; Anemia, run by Centre Hospitalier Annecy Genevois.
Trial summary
In patients with myelofibrosis, ruxolitinib is a current therapeutic option, which has demonstrated rapid and durable reduction in splenomegaly and improved disease-related symptoms. Anemia is another frequent issue in myelofibrosis. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myelofibrosis; Anemia
- How many people
- 65 participants
- Where
- No sites listed yet
- Study dates
- May 2016to 31 Dec 2016
- Phase
- Observational
- Are there results?
- None posted in the registry
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
Study population: Patients with myelofibroses treated with a combination of Janus Kinase 2 Inhibitor and Erythropoiesis-stimulating Agent in one of the France Intergroup Myeloproliferative neoplasms centers
Who may be able to join
- patients with primary myelofibrosis or post-polycythemia myelofibrosis or post-essential thrombocythemia myelofibrosis
- previously started with a combination of Janus Kinase 2 Inhibitor and Erythropoiesis-stimulating Agent, whatever the date during the course of their disease
Who cannot join
- patients who denied participating to this observational study
About this study
Official title: Patients With Myelofibrosis Treated With Combination of Janus Kinase 2 Inhibitor and Erythropoiesis-stimulating Agent. A French Observational Study.
In patients with myelofibrosis, ruxolitinib is a current therapeutic option, which has demonstrated rapid and durable reduction in splenomegaly and improved disease-related symptoms. Anemia is another frequent issue in myelofibrosis. Consistent with its JAK2 signalling inhibition, ruxolitinib therapy has been shown to be detrimental on the hemoglobin level, increasing the depth of anemia or transfusion need.
Despite potential antagonistic mechanisms of action on Janus Kinase 2, some responses on anemia have been reported with the addition of Erythropoiesis-stimulating Agent to ruxolitinib in a small subset of patients in the COMFORT II study.
Ruxo-EPO is an observational study aimed to better assess the combination of Erythropoiesis-stimulating Agent and a Janus Kinase 2 inhibitor for therapeutic efficacy on anemia, Myelofibrosis evolution and for tolerance, in a larger cohort of patients treated for myelofibrosis in general practice.
Read the detailed description
Myeloproliferative Neoplasms are chronic diseases; they encompass Polycythemia Vera, Essential Thrombocythemia, and Primary Myelofibrosis with shared mutations that constitutively activate the physiologic signal-transduction pathways responsible for hematopoiesis. Myelofibroses may arise either as primary or antecedent to Polycythemia Vera and Essential Thrombocythemia. Myelofibrosis is the least common and the most aggressive of these diseases leading to death in 5 to 7 years due to bone marrow failure, massive splenomegaly related to extra medullary hematopoiesis, constitutional symptoms and cachexia.
Until recently, treatment of Myelofibrosis consisted of supportive care only, especially transfusions.
Since 2005 driver mutations have been identified in more than 90% of patients with myeloproliferative neoplasms, providing substantial insight into their pathogenesis and leading to the development of JAK inhibitor drugs. Ruxolitinib, the first one available, has shown activity whatever the presence of Janus Kinase 2 mutation, in reducing splenomegaly, improving cytopenias, alleviating constitutional symptoms and finally improving survival (COMFORT I and II studies). In France, access to ruxolitinib has been possible since April 2011, before wider availability in November 2012.
Anemia is a frequent issue in Myelofibrosis, which may be managed by the use of Erythropoiesis-stimulating Agent, leading to a 40-50% response rate in small studies.
Consistent with its Janus Kinase 2 signalling inhibition, ruxolitinib therapy has been shown to be detrimental on the hemoglobin level, increasing the depth of anemia or transfusion need, especially during the first 12-24 weeks of treatment in the COMFORT studies.
Despite potential antagonistic mechanisms of action on Janus Kinase 2, some responses on anemia have been reported with the addition of Erythropoiesis-stimulating Agent to ruxolitinib in a small subset of patients in the COMFORT II study.
Ruxo-EPO is an observational study aimed to better assess the combination of Erythropoiesis-stimulating Agent and a Janus Kinase 2 inhibitor for therapeutic efficacy on anemia, Myelofibrosis evolution and for tolerance, in a larger cohort of patients treated for myelofibrosis in general practice.
- Conditions
- Myelofibrosis; Anemia
- Keywords
- Myelofibrosis, Erythropoiesis-stimulating Agents, Janus Kinase 2 inhibitors, Ruxolitinib
- Medical subject headings
- Primary Myelofibrosis, Anemia
What is being measured
The primary outcome is the main question the study is designed to answer.
Effect on anemia of the combination Janus Kinase 2 Inhibitor and Erythropoiesis-stimulating Agent
Response rate assessed with 2006 International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) and European Leukemia Network (ELN) criteria
Measured: 6 months
Secondary outcomes (8)
Patterns of the combination Janus Kinase 2 Inhibitor and Erythropoiesis-stimulating Agent
Modalities of the combination (drugs of interest begun at the same or at different dates, order of the drug combination if started at different dates, duration of combination, doses of each drug)
Measured: 6 months
Patients and Myelofibrosis characteristics
Demographic characteristics of included patients, Characteristics of diseases (date of diagnosis, primary or secondary myelofibrosis, prognostic scores, level of hemoglobin, transfusion dependency, splenomegaly, mutations, delay between myelofibrosis diagnosis and Jak2 inhibitor treatment)
Measured: at inclusion
Response rate of the combination treatment on constitutional symptoms of myelofibrosis
Measured: 3 years
Response rate of the combination treatment on splenomegaly
Splenomegaly size assessment
Measured: 3 years
Efficacy of the combination treatment on bone marrow fibrosis
Assessment of bone marrow fibrosis change if bone marrow biopsy has been done
Measured: 3 years
Efficacy of the combination treatment on Janus Kinase 2 allelic burden change
Assessment of Janus Kinase 2 allelic burden change if molecular evaluation has been done in blood
Measured: 3 years
Adverse Events on combination treatment
Measured: 3 years
Overall survival on combination treatment
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jul 2017
- Study startMay 2016
- Primary completion31 Dec 2016
- Study completion31 Dec 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Myelofibrosis; AnemiaStudies of the same condition, open and under way.
- 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
- Observational
- Observational model
- Case only
- Time perspective
- Other
- Enrolment
- 65 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centre Hospitalier Annecy Genevois
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Sandra Malak, MD, Principal investigator, Hôpital René Huguenin - Institut Curie - St Cloud - FranceLydia Roy, MD, Study director, Hôpital Henri Mondor - Créteil - FrancePascale Cony-Makhoul, MD, Study director, CH Annecy Genevois - Pringy - FranceMathieu Wemeau, MD, Study director, CH Arras
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03208803
- Sponsor's protocol ID
- 15-10_Ruxo-EPO
- Acronym
- Ruxo-EPO
- Status last verified
- Jul 2022
- First submitted
- 28 Jun 2017
- Last updated
- 20 Jul 2022
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Cervantes F. How I treat myelofibrosis. Blood. 2014 Oct 23;124(17):2635-42. doi: 10.1182/blood-2014-07-575373. Epub 2014 Sep 16.
PubMed 25232060James C, Ugo V, Le Couedic JP, Staerk J, Delhommeau F, Lacout C, Garcon L, Raslova H, Berger R, Bennaceur-Griscelli A, Villeval JL, Constantinescu SN, Casadevall N, Vainchenker W. A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera. Nature. 2005 Apr 28;434(7037):1144-8. doi: 10.1038/nature03546.
PubMed 15793561Verstovsek 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 investigators. Efficacy, safety, and survival with ruxolitinib in patients with myelofibrosis: results of a median 3-year follow-up of COMFORT-I. Haematologica. 2015 Apr;100(4):479-88. doi: 10.3324/haematol.2014.115840. Epub 2015 Jan 23.
PubMed 25616577Cervantes 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.
PubMed 24174625Ellis MH, Lavi N, Mishchenko E, Dally N, Lavie D, Courevitch A, Gutwein O, Bulvik S, Braester A, Chubar E, Tavor S, Duek A, Kirgner I, Koren-Michowitz M. Ruxolitinib treatment for myelofibrosis: Efficacy and tolerability in routine practice. Leuk Res. 2015 Aug 12:S0145-2126(15)30356-8. doi: 10.1016/j.leukres.2015.08.003. Online ahead of print.
PubMed 26364797McMullin 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.
PubMed 26380150Tefferi A, Cervantes F, Mesa R, Passamonti F, Verstovsek S, Vannucchi AM, Gotlib J, Dupriez B, Pardanani A, Harrison C, Hoffman R, Gisslinger H, Kroger N, Thiele J, Barbui T, Barosi G. Revised response criteria for myelofibrosis: International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) and European LeukemiaNet (ELN) consensus report. Blood. 2013 Aug 22;122(8):1395-8. doi: 10.1182/blood-2013-03-488098. Epub 2013 Jul 9.
PubMed 23838352
Study at a glance
From the registry record, last updated by the sponsor on 20 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Patients With Myelofibrosis Treated With Combination of Janus Kinase 2 Inhibitor and Erythropoiesis-stimulating Agent. A French Observational Study.
- ClinicalTrials.gov ID
- NCT03208803
- Acronym / sponsor ID
- Ruxo-EPO / 15-10_Ruxo-EPO
- Conditions
- Myelofibrosis; Anemia
- Keywords
- Myelofibrosis, Erythropoiesis-stimulating Agents, Janus Kinase 2 inhibitors, Ruxolitinib
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 65 participants (actual)
- Lead sponsor
- Centre Hospitalier Annecy GenevoisUniversity, hospital or other
- Study start
- May 2016 (actual)
- Primary completion
- 31 Dec 2016 (actual)
- Study completion
- 31 Dec 2016 (actual)
- First posted
- 6 Jul 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In patients with myelofibrosis, ruxolitinib is a current therapeutic option, which has demonstrated rapid and durable reduction in splenomegaly and improved disease-related symptoms. Anemia is another frequent issue in myelofibrosis. Consistent with its JAK2 signalling inhibition, ruxolitinib therapy has been shown to be detrimental on the hemoglobin level, increasing the depth of anemia or transfusion need.
Despite potential antagonistic mechanisms of action on Janus Kinase 2, some responses on anemia have been reported with the addition of Erythropoiesis-stimulating Agent to ruxolitinib in a small subset of patients in the COMFORT II study.
Ruxo-EPO is an observational study aimed to better assess the combination of Erythropoiesis-stimulating Agent and a Janus Kinase 2 inhibitor for therapeutic efficacy on anemia, Myelofibrosis evolution and for tolerance, in a larger cohort of patients treated for myelofibrosis in general practice.
Detailed description
Myeloproliferative Neoplasms are chronic diseases; they encompass Polycythemia Vera, Essential Thrombocythemia, and Primary Myelofibrosis with shared mutations that constitutively activate the physiologic signal-transduction pathways responsible for hematopoiesis. Myelofibroses may arise either as primary or antecedent to Polycythemia Vera and Essential Thrombocythemia. Myelofibrosis is the least common and the most aggressive of these diseases leading to death in 5 to 7 years due to bone marrow failure, massive splenomegaly related to extra medullary hematopoiesis, constitutional symptoms and cachexia.
Until recently, treatment of Myelofibrosis consisted of supportive care only, especially transfusions.
Since 2005 driver mutations have been identified in more than 90% of patients with myeloproliferative neoplasms, providing substantial insight into their pathogenesis and leading to the development of JAK inhibitor drugs. Ruxolitinib, the first one available, has shown activity whatever the presence of Janus Kinase 2 mutation, in reducing splenomegaly, improving cytopenias, alleviating constitutional symptoms and finally improving survival (COMFORT I and II studies). In France, access to ruxolitinib has been possible since April 2011, before wider availability in November 2012.
Anemia is a frequent issue in Myelofibrosis, which may be managed by the use of Erythropoiesis-stimulating Agent, leading to a 40-50% response rate in small studies.
Consistent with its Janus Kinase 2 signalling inhibition, ruxolitinib therapy has been shown to be detrimental on the hemoglobin level, increasing the depth of anemia or transfusion need, especially during the first 12-24 weeks of treatment in the COMFORT studies.
Despite potential antagonistic mechanisms of action on Janus Kinase 2, some responses on anemia have been reported with the addition of Erythropoiesis-stimulating Agent to ruxolitinib in a small subset of patients in the COMFORT II study.
Ruxo-EPO is an observational study aimed to better assess the combination of Erythropoiesis-stimulating Agent and a Janus Kinase 2 inhibitor for therapeutic efficacy on anemia, Myelofibrosis evolution and for tolerance, in a larger cohort of patients treated for myelofibrosis in general practice.
Study design
- Observational model
- Case only
- Time perspective
- Other
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with myelofibroses treated with a combination of Janus Kinase 2 Inhibitor and Erythropoiesis-stimulating Agent in one of the France Intergroup Myeloproliferative neoplasms centers
Key inclusion criteria (2 listed)
- patients with primary myelofibrosis or post-polycythemia myelofibrosis or post-essential thrombocythemia myelofibrosis
- previously started with a combination of Janus Kinase 2 Inhibitor and Erythropoiesis-stimulating Agent, whatever the date during the course of their disease
Key exclusion criteria (1 listed)
- patients who denied participating to this observational study
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Effect on anemia of the combination Janus Kinase 2 Inhibitor and Erythropoiesis-stimulating Agent
Time frame: 6 months
Response rate assessed with 2006 International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) and European Leukemia Network (ELN) criteria
8 secondary outcomes
Patterns of the combination Janus Kinase 2 Inhibitor and Erythropoiesis-stimulating Agent
Time frame: 6 months
Patients and Myelofibrosis characteristics
Time frame: at inclusion
Response rate of the combination treatment on constitutional symptoms of myelofibrosis
Time frame: 3 years
Response rate of the combination treatment on splenomegaly
Time frame: 3 years
Efficacy of the combination treatment on bone marrow fibrosis
Time frame: 3 years
Efficacy of the combination treatment on Janus Kinase 2 allelic burden change
Time frame: 3 years
Adverse Events on combination treatment
Time frame: 3 years
Overall survival on combination treatment
Time frame: 3 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jul 2022.
- Background: PubMed 25232060Cervantes F. How I treat myelofibrosis. Blood. 2014 Oct 23;124(17):2635-42. doi: 10.1182/blood-2014-07-575373. Epub 2014 Sep 16.
- Background: PubMed 15793561James C, Ugo V, Le Couedic JP, Staerk J, Delhommeau F, Lacout C, Garcon L, Raslova H, Berger R, Bennaceur-Griscelli A, Villeval JL, Constantinescu SN, Casadevall N, Vainchenker W. A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera. Nature. 2005 Apr 28;434(7037):1144-8. doi: 10.1038/nature03546.
- Background: PubMed 25616577Verstovsek 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 investigators. Efficacy, safety, and survival with ruxolitinib in patients with myelofibrosis: results of a median 3-year follow-up of COMFORT-I. Haematologica. 2015 Apr;100(4):479-88. doi: 10.3324/haematol.2014.115840. Epub 2015 Jan 23.
- Background: PubMed 24174625Cervantes 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.
- Background: PubMed 26364797Ellis MH, Lavi N, Mishchenko E, Dally N, Lavie D, Courevitch A, Gutwein O, Bulvik S, Braester A, Chubar E, Tavor S, Duek A, Kirgner I, Koren-Michowitz M. Ruxolitinib treatment for myelofibrosis: Efficacy and tolerability in routine practice. Leuk Res. 2015 Aug 12:S0145-2126(15)30356-8. doi: 10.1016/j.leukres.2015.08.003. Online ahead of print.
- Background: PubMed 26380150McMullin 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.
- Background: PubMed 23838352Tefferi A, Cervantes F, Mesa R, Passamonti F, Verstovsek S, Vannucchi AM, Gotlib J, Dupriez B, Pardanani A, Harrison C, Hoffman R, Gisslinger H, Kroger N, Thiele J, Barbui T, Barosi G. Revised response criteria for myelofibrosis: International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) and European LeukemiaNet (ELN) consensus report. Blood. 2013 Aug 22;122(8):1395-8. doi: 10.1182/blood-2013-03-488098. Epub 2013 Jul 9.
- Individual participant dataSharing planned: No
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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.
Sandra Malak, MD principal investigator
Hôpital René Huguenin - Institut Curie - St Cloud - France
Lydia Roy, MD study director
Hôpital Henri Mondor - Créteil - France
Pascale Cony-Makhoul, MD study director
CH Annecy Genevois - Pringy - France
Questions about this trial
What is this clinical trial studying?
An observational study of Myelofibrosis; Anemia, run by Centre Hospitalier Annecy Genevois.
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 2 inclusion and 1 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 20 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.
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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Effect on anemia of the combination Janus Kinase 2 Inhibitor and Erythropoiesis-stimulating Agent (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03208803, which also lists 7 linked publications.
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 20 Jul 2022.