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

NCT02962388 | Terminated Phase 2 DMC

• 1 other identifier: RUXBETA trial
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

Prospective national multicenter randomized open label phase IIb RUXBETA trial.

Conditions

Essential Thrombocythemia

Keywords

efficacy; safety

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Complete hematologic response

  48 months

• AE/SAE

  48 months

• Median dose

  48 months

• Thrombotic and hemorrhagic events

  48 months

• Quality of life questionnaire

  48 months

Study Arms (2)

Reference therapy arm

ACTIVE COMPARATOR

Best Available Therapy (BAT) in second line, after hydroxyurea. BAT restricted to anagrelide or IFNα/ PegIFNα in the study, according to the investigator decision

Drug: Anagrelide; Drug: IFNα/ PegIFNα

Investigational therapy arm

EXPERIMENTAL

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.

Drug: Ruxolitinib (JAKAVI®)

Interventions

Anagrelide DRUG

Anagrelide in the study, according to the investigator decision fom day 1 to 48 months

Also known as: ARM A

Reference therapy arm

Ruxolitinib (JAKAVI®) DRUG

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

Also known as: ARM B

Investigational therapy arm

IFNα/ PegIFNα DRUG

IFNα/ PegIFNα in the study, according to the investigator decision fom day 1 to 48 months

Also known as: ARM A

Reference therapy arm

Eligibility Criteria

• Age: 18 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).
• History of significant bleeding disorder not related to the ET.
• Diagnosed congenital bleeding disorders,

Sponsors & Collaborators

• French Innovative Leukemia Organisation: lead
• Novartis Pharmaceuticals: collaborator

Study Sites (1)

FILO

Tours, 37044, France

Location

Related Links

• FILO site

MeSH Terms

Conditions

Thrombocythemia, Essential

Interventions

anagrelide; ruxolitinib

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Thrombocytosis; Blood Platelet Disorders; Myeloproliferative Disorders; Bone Marrow Diseases; Hemorrhagic Disorders

Study Officials

• Stéphane GIRAUDIER, MD PD

  France Intergroupe Syndromes Myéloprolifératifs

  PRINCIPAL INVESTIGATOR

• LYDIA ROY, MD

  France Intergroupe Syndromes Myéloprolifératifs

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 5, 2016
• First Posted: November 11, 2016
• Study Start: January 3, 2017
• Primary Completion: June 28, 2021
• Study Completion: June 28, 2021
• Last Updated: June 29, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will share

Locations

FR (1)