- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02962388
The Ruxolitinib Versus Best Available Therapy Trial in Patients With High Risk ET in Second Line
A Randomized, Multicenter Phase IIb Study to Evaluate the Efficacy and Safety of Ruxolitinib Versus Best Available Therapy in Patients With High Risk Essential Thrombocythemia, Who Are Resistant or Intolerant to Hydroxyurea: A FIM Study
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 3
Contacts and Locations
Study Locations
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Tours, France, 37044
- FILO
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
Target Population
- Men and women, age more than or equal18 years and less than 75 years.
- Confirmed diagnosis of Essential Thrombocythemia for at least 6 months, according to the 2008 WHO criteria, with a high-risk status.
Patients must have a treatment history for ET that meet the definition of resistance or intolerance to hydroxyurea therapy according to the ELN criteria as follow:
- Platelets more than 600.0109/L after 3 months (12 weeks) of treatment at a dose over 2g/day.
- Platelets more than 400.0 109/L and WBC less than 2.5109/L, whatever the dose of HU.
- Platelets more than 400.0 109/L and Hb less than 10g/dl whatever the dose of HU.
- Leg ulcers or other unacceptable muco-cutaneous toxicity.
- HU-related fever.
- ECOG Performance Status (ECOG PS) less than or equal 2 at screening and at baseline.
Adequate Organ Function:
- Direct bilirubin less than 2.0 times the institutional Upper Limit of Normal (ULN).
- Hepatic enzymes (AST, ALT) less than or equal 2.5 times the institutional ULN.
- Adequate renal function at screening as demonstrated by MDRD-eGFR more than 30 mL/min/1.73m2.
Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy during and after the study.
- A male subject of fathering potential must use an adequate method of contraception to avoid conception during and after the study to minimize the risk of pregnancy.
- For females and males, these restrictions apply for 24 hours after the last dose of study drug.
- Women of childbearing potential must have a negative serum (beta-human chorionic gonadotropin hCG pregnancy test at Screening.
- Signed Written Informed Consent.
- Health insurance coverage.
Exclusion Criteria:
- Patients with thrombocytosis related to another MPN than ET
- Patients previously treated with a JAK2 inhibitor, Anagrelide or Interferon-alpha and prior history of therapy other than Hydroxyurea
- Contraindication to Ruxolitinib, Anagrelide or Interferon-alpha (if no eligible for anagrelide), hypersensitivity to an excipient
Medical history and concurrent diseases:
- Clinically significant cardiac disease (NYHA Class III or IV).
- Chronic hepatocellular disease.
- Subjects with impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of Ruxolitinib
Subjects with clinically significant bacterial, fungal, parasitic or viral infection which requires therapy:
- Subjects with acute bacterial infections requiring antibiotic use should delay screening/enrolment until the course of antibiotic therapy has been completed.
- Subjects with active hepatitis A, B or C or with HIV positivity at screening.
- Subjects with diagnosed primary immunodeficiency syndromes such as X-Linked a gammaglobulinemia and common variable immune deficiency.
- Subject with medical history of tuberculosis
- History of progressive multifocal leucoencephalopathy (PML).
- Other malignant disease during the last 5 years prior to the inclusion except treated cervical intraepithelial neoplasia, basal cell carcinoma of the skin, or squamous cell carcinoma of the skin, with no evidence for recurrence in the past 3 years.
History of significant bleeding disorder not related to the ET.
- Diagnosed congenital bleeding disorders,
- Diagnosed acquired bleeding disorder within one year (e.g. acquired anti-factor VIII antibodies),
- Ongoing or recent (3 months) significant gastrointestinal bleeding.
- Subjects with an uncontrolled undercurrent illness or any concurrent condition that, in the investigator's opinion, would jeopardize the safety of the subject or compliance with the protocol.
- Subjects being treated concurrently with a potent systemic inhibitor of CYP3A4 at the time of screening.
- Subjects being treated concurrently with any prohibited medications.
- Women who are pregnant or breastfeeding are not eligible for this study.
- Inability to freely provide consent through judiciary or administrative condition.
- Ongoing participation to another clinical investigational study.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Active Comparator: Reference therapy arm
Best Available Therapy (BAT) in second line, after hydroxyurea.
BAT restricted to anagrelide or IFNα/ PegIFNα in the study, according to the investigator decision
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Anagrelide in the study, according to the investigator decision fom day 1 to 48 months
Other Names:
IFNα/ PegIFNα in the study, according to the investigator decision fom day 1 to 48 months
Other Names:
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Experimental: Investigational therapy arm
Ruxolitinib JAKAVI® Starting dose 10 mg BID, orally. To be increased or decreased (5 or 10 mg steps) per standardized dosing paradigm. Maximum dose 25 mg BID. |
Ruxolitinib (JAKAVI®) - Novartis.
Tablets 5 mg.
Starting dose 10 mg BID, orally.
To be increased or decreased (5 or 10 mg steps) per standardized dosing Maximum dose 25 mg BID.
fom day 1 to 48 months
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Failure-free patients
Time Frame: month 12
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Failure is defined by the occurrence of either intolerance and/or resistance to the second line therapy according to the protocol criteria
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month 12
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Complete hematologic response
Time Frame: 48 months
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Number of Participants With normal Laboratory Values
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48 months
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AE/SAE
Time Frame: 48 months
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Rates, types and grades of AE/SAE related to the therapy, according to the NCI-CTCAE v4.0 classification
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48 months
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Median dose
Time Frame: 48 months
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Median dose of the treatment received
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48 months
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Thrombotic and hemorrhagic events
Time Frame: 48 months
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Cumulative incidence of thrombotic and hemorrhagic events incidence of progression into PV, secondary MF and MDS/acute leukemia
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48 months
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Quality of life questionnaire
Time Frame: 48 months
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Quality of life
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48 months
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Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Stéphane GIRAUDIER, MD PD, France Intergroupe Syndromes Myéloprolifératifs
- Principal Investigator: LYDIA ROY, MD, France Intergroupe Syndromes Myéloprolifératifs
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Bone Marrow Diseases
- Hematologic Diseases
- Hemorrhagic Disorders
- Myeloproliferative Disorders
- Blood Coagulation Disorders
- Blood Platelet Disorders
- Thrombocytosis
- Thrombocythemia, Essential
- Molecular Mechanisms of Pharmacological Action
- Fibrinolytic Agents
- Fibrin Modulating Agents
- Platelet Aggregation Inhibitors
- Anagrelide
Other Study ID Numbers
- RUXBETA trial
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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