JAK2 Inhibitors RUXOLITINIB in Patients With Myelofibrosis

Study Overview
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Brief Summary
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JAK2 inhibitor RUXOLITINIB before allogeneic hematopoietic stem cell transplantation (HSCT) in patients with primary or secondary myelofibrosis : a prospective phase II

Detailed Description
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JAK2 inhibitor RUXOLITINIB before allogeneic hematopoietic stem cell transplantation (HSCT) in patients with primary or secondary myelofibrosis

Official Title
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JAK2 Inhibitors RUXOLITINIB in Patients With High or Intermediate Risk Primary or Secondary Myelofibrosis Eligible for Allogeneic Stem Cell Transplantation: a Prospective Multicentric Phase II Study

Conditions
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Myelofibrosis

Intervention / Treatment
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* Drug: Ruxolotinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between 18 and 69 years No comorbidity contraindicating the transplantation : Severe respiratory failure defined as dyspnea grade III or more Severe cardiac failure defined as EF < or = 30% Severe renal failure defined as creatinine clearance < 30 ml/min or dialysis Dementia or non-ability to give informed consent for the protocol Major alteration of performance status defined as ECOG > 2 Severe liver disease defined as a cirrhosis or bilirubin > 2 x ULN, or AST/ALT > 5 x ULN Primary or secondary myelofibrosis diagnosed according to WHO definition (Tefferi, et al 2007) Palpable splenomegaly or splenomegaly measured by any imagery (maximum size> 15 cm by ultrasound scan, Magnetic Resonance Imaging or computer tomography) Disease if intermediate or high risk according to published criteria and summarized as follows: At least one criterion among the following: Haemoglobin < 100 gr/L (unrelated to medication toxicity) Leucocytes < 4 G/L (unrelated to medication toxicity) or > 25 G/L Poor prognosis cytogenetics : complex karyotype, abnormalities of chromosomes 5, 7 or 17 , +8, 12p-, inv(3), 11q23 Two criteria among the following criteria : General symptoms (weight lost > 10% in less than 6 months, night swears, specific fever > 37.5°C) Peripheral blastosis > 1% observed at least twice Thrombocytopenia < 100 G/L (unrelated to treatment toxicity) Exclusion Criteria: Myelofibrosis transformed into acute leukaemia with 20% blasts of more in blood or bone marrow Previous treatment with JAK2 inhibitor Thrombopenia < 50 G/L Comorbidities contraindicating the transplantation Comorbidity score Sorror > 3 Pregnant or lactating women

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 69 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RUXOLOTINIB<br>Ruxolotinib : patient with donor HSCT 4 months later patients without donor: ruxolotinib alone | Drug: Ruxolotinib<br>* Ruxolotinib doses calculated with platelets count and P450 cytochrome inhibitor HSCT for patients with donor<br>* Other names: Kakavi;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DFS | DFS is defined as the probability to be alive and in remission | 24 months after inclusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HSCT | Rate of pre-graft splenectomy Co-morbidity score defined by Sorror et al before RUXOLITINIB and after 4-month treatment just before transplantation Post-graft haematological recovery: time to neutrophil engraftment, platelet and red blood cells transfusion independency Acute GVHD grade II-IV incidence Chronic GVHD incidence Overall survival, disease-free survival, non-relapse mortality JAK2V617E allele burden and status at registration, 3, 7, 16 months after inclusion (centralization) | 24 months after inclusion | 
| PATIENTS CARACTERISTICS | Patients with and without donor Rate of patients with donor who benefit from a transplantation: Comorbidity score at registration and after 3 months Platelet and red blood cells transfusion independency Performance status evolution (ECOG) General symptoms related to myelofibrosis (questionnaire MF SAF) Comparison of haematological response in patients with or without donor Spleen size evolution Comparison of quality of life in patients with and without (questionnaire EORTC) Comparison of overall survival in patients with and without donor Incidence of severe infections Cytokine measure at registration, 3, and 7 months after inclusion (centralization) MPL JAK status (at registration, centralization | 24 months after inclusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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JAK2 inhibitor RUXOLITINIB, Primary or secondary myelofibrosis