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Combination of JAK2 Inhibitor and Erythropoiesis-stimulating Agent in Myelofibrosis (Ruxo-EPO)

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ClinicalTrials.gov Identifier: NCT03208803
Recruitment Status : Active, not recruiting
First Posted : July 6, 2017
Last Update Posted : June 17, 2019
Sponsor:
Information provided by (Responsible Party):
Centre Hospitalier Annecy Genevois

Brief 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. 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.


Condition or disease
Myelofibrosis; Anemia

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.

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Study Type : Observational
Actual Enrollment : 65 participants
Observational Model: Case-Only
Time Perspective: Other
Official Title: Patients With Myelofibrosis Treated With Combination of Janus Kinase 2 Inhibitor and Erythropoiesis-stimulating Agent. A French Observational Study.
Actual Study Start Date : May 2016
Actual Primary Completion Date : December 30, 2017
Estimated Study Completion Date : December 31, 2020





Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. Patterns of the combination Janus Kinase 2 Inhibitor and Erythropoiesis-stimulating Agent [ Time Frame: 6 months ]
    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)

  2. Patients and Myelofibrosis characteristics [ Time Frame: at inclusion ]
    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)

  3. Response rate of the combination treatment on constitutional symptoms of myelofibrosis [ Time Frame: 3 years ]
  4. Response rate of the combination treatment on splenomegaly [ Time Frame: 3 years ]
    Splenomegaly size assessment

  5. Efficacy of the combination treatment on bone marrow fibrosis [ Time Frame: 3 years ]
    Assessment of bone marrow fibrosis change if bone marrow biopsy has been done

  6. Efficacy of the combination treatment on Janus Kinase 2 allelic burden change [ Time Frame: 3 years ]
    Assessment of Janus Kinase 2 allelic burden change if molecular evaluation has been done in blood

  7. Adverse Events on combination treatment [ Time Frame: 3 years ]
  8. Overall survival on combination treatment [ Time Frame: 3 years ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
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
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

- patients who denied participating to this observational study


Information from the National Library of Medicine

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): NCT03208803


Sponsors and Collaborators
Centre Hospitalier Annecy Genevois
Investigators
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Principal Investigator: Sandra Malak, MD Hôpital René Huguenin - Institut Curie - St Cloud - France
Study Director: Lydia Roy, MD Hôpital Henri Mondor - Créteil - France
Study Director: Pascale Cony-Makhoul, MD CH Annecy Genevois - Pringy - France
Study Director: Mathieu Wemeau, MD CH Arras
Additional Information:
Publications:

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Responsible Party: Centre Hospitalier Annecy Genevois
ClinicalTrials.gov Identifier: NCT03208803    
Other Study ID Numbers: 15-10_Ruxo-EPO
First Posted: July 6, 2017    Key Record Dates
Last Update Posted: June 17, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Centre Hospitalier Annecy Genevois:
Myelofibrosis
Erythropoiesis-stimulating Agents
Janus Kinase 2 inhibitors
Ruxolitinib
Additional relevant MeSH terms:
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Primary Myelofibrosis
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases