JAK2 Inhibitors RUXOLITINIB in Patients With Myelofibrosis

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2013 by Groupe Ouest Est d'Etude des Leucémies et Autres Maladies du Sang GOELAMS
Sponsor:
Information provided by (Responsible Party):
Groupe Ouest Est d'Etude des Leucémies et Autres Maladies du Sang GOELAMS
ClinicalTrials.gov Identifier:
NCT01795677
First received: December 21, 2012
Last updated: June 24, 2013
Last verified: February 2013
  Purpose

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


Condition Intervention Phase
Myelofibrosis
Drug: Ruxolotinib
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Groupe Ouest Est d'Etude des Leucémies et Autres Maladies du Sang GOELAMS:

Primary Outcome Measures:
  • DFS [ Time Frame: 24 months after inclusion ] [ Designated as safety issue: Yes ]
    DFS is defined as the probability to be alive and in remission


Secondary Outcome Measures:
  • HSCT [ Time Frame: 24 months after inclusion ] [ Designated as safety issue: Yes ]
    • 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)

  • PATIENTS CARACTERISTICS [ Time Frame: 24 months after inclusion ] [ Designated as safety issue: Yes ]

    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


Estimated Enrollment: 80
Study Start Date: December 2012
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

Detailed Description:

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

  Eligibility

Ages Eligible for Study:   18 Years to 69 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01795677

Contacts
Contact: Marie ROBIN, MD 33142499639 marie.robin@sls.aphp.fr
Contact: Valerie ROLLAND NEYRET, CRA 33 476765096 VRolland-neyret@chu-grenoble.fr

Locations
France
ROBIN Recruiting
Paris, France, 75010
Contact: Valerie ROLLAND NEYRET, Mrs    +3476765096    vrOlland-neyret@chu-grenoble.fr   
Principal Investigator: Marie ROBIN, MD         
Sponsors and Collaborators
Groupe Ouest Est d'Etude des Leucémies et Autres Maladies du Sang GOELAMS
Investigators
Principal Investigator: MARIE ROBIN, MD FIM/GOELAMS
  More Information

Additional Information:
No publications provided

Responsible Party: Groupe Ouest Est d'Etude des Leucémies et Autres Maladies du Sang GOELAMS
ClinicalTrials.gov Identifier: NCT01795677     History of Changes
Other Study ID Numbers: JAK ALLO STUDY
Study First Received: December 21, 2012
Last Updated: June 24, 2013
Health Authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé

Keywords provided by Groupe Ouest Est d'Etude des Leucémies et Autres Maladies du Sang GOELAMS:
JAK2 inhibitor RUXOLITINIB
Primary or secondary myelofibrosis

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

ClinicalTrials.gov processed this record on August 19, 2014