The Ruxolitinib Versus Best Available Therapy Trial in Patients With High Risk ET in Second Line

June 28, 2021 updated by: French Innovative Leukemia Organisation

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

Prospective national multicenter randomized open label phase IIb RUXBETA trial.

Study Overview

Detailed Description

A randomized, open label, 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.

Study Type

Interventional

Enrollment (Actual)

13

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Tours, France, 37044
        • FILO

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 72 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

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
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
Anagrelide in the study, according to the investigator decision fom day 1 to 48 months
Other Names:
  • ARM A
IFNα/ PegIFNα in the study, according to the investigator decision fom day 1 to 48 months
Other Names:
  • ARM A
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:
  • ARM B

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Failure-free patients
Time Frame: month 12
Failure is defined by the occurrence of either intolerance and/or resistance to the second line therapy according to the protocol criteria
month 12

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Complete hematologic response
Time Frame: 48 months
Number of Participants With normal Laboratory Values
48 months
AE/SAE
Time Frame: 48 months
Rates, types and grades of AE/SAE related to the therapy, according to the NCI-CTCAE v4.0 classification
48 months
Median dose
Time Frame: 48 months
Median dose of the treatment received
48 months
Thrombotic and hemorrhagic events
Time Frame: 48 months
Cumulative incidence of thrombotic and hemorrhagic events incidence of progression into PV, secondary MF and MDS/acute leukemia
48 months
Quality of life questionnaire
Time Frame: 48 months
Quality of life
48 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

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

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 3, 2017

Primary Completion (Actual)

June 28, 2021

Study Completion (Actual)

June 28, 2021

Study Registration Dates

First Submitted

October 5, 2016

First Submitted That Met QC Criteria

November 9, 2016

First Posted (Estimate)

November 11, 2016

Study Record Updates

Last Update Posted (Actual)

June 29, 2021

Last Update Submitted That Met QC Criteria

June 28, 2021

Last Verified

June 1, 2021

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

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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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