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

Essential Thrombocythemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02962388
• Other study ID #: RUXBETA trial
• Status: Terminated
• Phase: Phase 2/Phase 3
• Start date: January 3, 2017
• Est. completion date: June 28, 2021

Study information

• Verified date: June 2021
• Source: French Innovative Leukemia Organisation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Prospective national multicenter randomized open label phase IIb RUXBETA trial.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 13
• Est. completion date: June 28, 2021
• Est. primary completion date: June 28, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 74 Years

Eligibility

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.

Related Conditions & MeSH terms

• Essential Thrombocythemia
• Thrombocythemia, Essential
• Thrombocytosis

Intervention

Drug:
• Anagrelide
Anagrelide in the study, according to the investigator decision fom day 1 to 48 months
• Ruxolitinib (JAKAVI®)
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
• IFNa/ PegIFNa
IFNa/ PegIFNa in the study, according to the investigator decision fom day 1 to 48 months

Locations

Country	Name	City	State
France	FILO	Tours

Sponsors (2)

Lead Sponsor	Collaborator
French Innovative Leukemia Organisation	Novartis Pharmaceuticals

Country where clinical trial is conducted

France, 

Outcome

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

External Links

•   FILO site