JAK2 Inhibitors RUXOLITINIB in Patients With Myelofibrosis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01795677
Recruitment Status : Active, not recruiting
First Posted : February 21, 2013
Last Update Posted : April 27, 2018
Information provided by (Responsible Party):
French Innovative Leukemia Organisation

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

Condition or disease Intervention/treatment Phase
Myelofibrosis Drug: Ruxolotinib Phase 2

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

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 78 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : December 2012
Estimated Primary Completion Date : May 2018
Estimated Study Completion Date : March 2019

Arm Intervention/treatment
Experimental: RUXOLOTINIB
Ruxolotinib : patient with donor HSCT 4 months later patients without donor: ruxolotinib alone
Drug: Ruxolotinib
Ruxolotinib doses calculated with platelets count and P450 cytochrome inhibitor HSCT for patients with donor
Other Name: Kakavi

Primary Outcome Measures :
  1. DFS [ Time Frame: 24 months after inclusion ]
    DFS is defined as the probability to be alive and in remission

Secondary Outcome Measures :
  1. HSCT [ Time Frame: 24 months after inclusion ]
    • 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)

  2. PATIENTS CARACTERISTICS [ Time Frame: 24 months after inclusion ]

    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

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Ages Eligible for Study:   18 Years to 69 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

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 identifier (NCT number): NCT01795677

Paris, France, 75010
Sponsors and Collaborators
French Innovative Leukemia Organisation
Principal Investigator: MARIE ROBIN, MD FIM/GOELAMS

Additional Information:
Responsible Party: French Innovative Leukemia Organisation Identifier: NCT01795677     History of Changes
Other Study ID Numbers: JAK ALLO STUDY
First Posted: February 21, 2013    Key Record Dates
Last Update Posted: April 27, 2018
Last Verified: April 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by French Innovative Leukemia Organisation:
Primary or secondary myelofibrosis

Additional relevant MeSH terms:
Primary Myelofibrosis
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases