A Study to Evaluate the Efficacy and Safety of Vismodegib in Combination With Ruxolitinib for the Treatment of Intermediate- or High-Risk Myelofibrosis (MF)

May 4, 2018 updated by: Hoffmann-La Roche

A Phase IB/III, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Vismodegib in Combination With Ruxolitinib Versus Placebo and Ruxolitinib in Patients With Intermediate- or High-Risk Myelofibrosis

This multicenter, randomized, double-blind, placebo-controlled study will evaluate the efficacy and safety of vismodegib plus (+) ruxolitinib versus placebo + ruxolitinib in participants with intermediate- or high-risk MF. The study will be divided into 2 components. The Phase Ib portion of the study consists of participants receiving open-label vismodegib (150 milligrams [mg] orally [PO] once daily [QD]) + ruxolitinib (PO twice daily [BID]). A safety assessment will be performed after the first 10 participants have been treated for 6 weeks. An analysis for efficacy and safety is planned in the first 10 participants at Week 24. There will be a hold on participant screening and enrollment during this assessment. Another 10 participants may be enrolled, thereafter, to further assess efficacy and safety (at Week 24) before the initiation of the Phase III randomization portion of the study. Similarly, there will be another hold on participant screening and enrollment during this assessment. The participants enrolled in the Phase Ib portion of the study will continue to receive vismodegib (150 mg PO QD) + ruxolitinib (PO BID) for up to 48 weeks, if clinical benefit is observed after 24 weeks. The Phase III randomized, double-blind portion of the study will enroll approximately 84 participants. Participants will be randomly assigned in a 1:1 ratio (double blind) to receive either vismodegib (150 mg PO QD) + ruxolitinib (PO BID) or placebo (PO QD) + ruxolitinib (PO BID) for up to 48 weeks.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
10

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

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

  • Canada
    • Alberta
      • Calgary, Alberta, Canada, T2N 4N2
        • Tom Baker Cancer Centre-Calgary; Clinical Research Unit
    • Nova Scotia
      • Halifax, Nova Scotia, Canada, B3H 2Y9
        • Queen Elizabeth II Health Sciences Centre; Oncology
    • Quebec
      • Montreal, Quebec, Canada, H2L 4M1
        • Centre Hospitalier De L'Universite De Montreal, Hopital Notre-Dame
  • Germany
      • Aachen, Germany, 52074
        • Uniklinik RWTH Aachen; Med. Klinik IV; Klinik für Hämatologie, Onkologie, Hämostaseologie und Stammz
      • Berlin, Germany, 13353
        • Campus Virchow-Klinikum Charité Centrum 14; Medizinische Klinik m.S. Hämatologie u. Onkologie
  • Italy
    • Piemonte
      • Torino, Piemonte, Italy, 10126
        • A.O.U. Citta' Della Salute E Della Scienza-P.O. Molinette;S.C. Ematologia
    • Toscana
      • Firenze, Toscana, Italy, 50135
        • Az. Osp. Di Careggi; Divisione Di Ematologia
  • United States
    • Florida
      • Fort Myers, Florida, United States, 33908
        • Florida Cancer Specialists-Broadway, Fort Myers
      • Saint Petersburg, Florida, United States, 33705
        • Florida Cancer Specialist, North Region
      • West Palm Beach, Florida, United States, 33401
        • Florida Cancer Specialists
    • Ohio
      • Cincinnati, Ohio, United States, 45242
        • Oncology Hematology Care Inc
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Sarah Cannon Research Institute
    • Texas
      • Houston, Texas, United States, 77030
        • Uni of Texas - Md Anderson Cancer Center; Dept of Leukemia

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Pathologically confirmed diagnosis of primary MF, post-polycythemia vera MF, or post-essential thrombocythemia MF, according to the 2008 revised World Health Organization criteria
  • Intermediate-1, intermediate-2, or high-risk according to the IWG-MRT Dynamic International Prognostic Scoring System
  • Life expectancy >= 6 months
  • Peripheral blood blast count of less than (<) 10%
  • Palpable splenomegaly of greater than (>) 5 centimeters (cm) below the left costal margin
  • Eastern Cooperative Oncology Group performance status of 0 to 2
  • Adequate hepatic and renal function

Exclusion Criteria:

  • Prior treatment with a Hedgehog or Janus kinase pathway inhibitor
  • Treatment with strong cytochrome P450 3A4 inhibitors/inducers within 28 days prior to Day 1
  • Prior therapy for the treatment of intermediate- or high-risk MF including chemotherapy, interferon, thalidomide, busulfan, lenalidomide, anagrelide, or androgens within 28 days prior to Day 1
  • Prior splenectomy or splenic irradiation
  • Inadequate bone marrow reserve
  • Participants with any history of platelet counts of < 50,000/mccL or ANC of < 500/mL, except during treatment for myeloproliferative neoplasm or treatment with cytotoxic therapy for any other reason
  • Planned allogeneic bone marrow transplant during the 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: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Placebo + Ruxolitinib
Participants will receive placebo (PO QD) in combination with ruxolitinib (dose will depend on the participant's baseline platelet count) for up to 48 weeks.
Other: Placebo
Placebo will be administered PO QD for up to 48 weeks.
Drug: Ruxolitinib
Ruxolitinib will be administered PO BID at a starting dose depending on the participants's baseline platelet count for up to 48 weeks.
Experimental: Vismodegib + Ruxolitinib
Participants will receive vismodegib (150 mg PO QD) in combination with ruxolitinib (dose will depend on the participant's baseline platelet count) for up to 48 weeks.
Drug: Ruxolitinib
Ruxolitinib will be administered PO BID at a starting dose depending on the participants's baseline platelet count for up to 48 weeks.
Drug: Vismodegib
Vismodegib will be administered at a dose of 150 mg PO QD for up to 48 weeks.
Other Names:
  • Erivedge

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Percentage of Participants who Achieve a Greater Than or Equal to (>=) 35% Reduction in Spleen Volume from Baseline at Week 24
Time Frame: Week 24
Determined by an Independent Review Committee (IRC) Using International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) Revised Response Criteria
Week 24
Percentage of Participants with Complete Remission (CR) and Partial Remission (PR) at Week 24, as Determined by an IRC Using IWG-MRT Revised Response Criteria
Time Frame: Week 24
Week 24

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Plasma Vismodegib Concentration at Steady State
Time Frame: Predose (0 hour) on Weeks 6, 12, 24, 36, and 48
Predose (0 hour) on Weeks 6, 12, 24, 36, and 48
Unbound Vismodegib Concentration at Steady State
Time Frame: Predose (0 hour) on Weeks 6, 12, 24, 36, and 48
Predose (0 hour) on Weeks 6, 12, 24, 36, and 48
Alpha 1-Acid Glycoprotein Concentration at Steady State
Time Frame: Predose (0 hour) on Weeks 6, 12, 24, 36, and 48
Predose (0 hour) on Weeks 6, 12, 24, 36, and 48
Percentage of Participants who Achieve a >= 35% Reduction in Spleen Volume from Baseline, as Determined by an IRC Using IWG-MRT Revised Response Criteria at Week 48
Time Frame: Baseline, Week 48
Baseline, Week 48
Percentage of Participants who Achieve a >= 35% Reduction in Spleen Volume from Baseline, as Determined by an Investigator at Weeks 24 and 48
Time Frame: Baseline, Weeks 24 and 48
Baseline, Weeks 24 and 48
Percentage of Participants with CR and PR, as Determined by an IRC Using IWG-MRT Revised Response Criteria at Week 48
Time Frame: Week 48
Week 48
Percentage of Participants with CR and PR, as Determined by an Investigator at Weeks 24 and 48
Time Frame: Weeks 24 and 48
Weeks 24 and 48
Percentage of Participants with Overall Response Rate (CR, PR, and Clinical Improvement) at Weeks 24 and 48, as Determined by an IRC Using IWG-MRT Revised Response Criteria
Time Frame: Weeks 24 and 48
Weeks 24 and 48
Percentage of Participants with Overall Response Rate (CR, PR, and Clinical Improvement) at Weeks 24 and 48, as Determined by the Investigator Using IWG-MRT Revised Response Criteria
Time Frame: Weeks 24 and 48
Weeks 24 and 48
Percentage of Participants who Achieve Anemia Response at Weeks 24 and 48, as Determined by the Investigator Using IWG-MRT Revised Response Criteria
Time Frame: Weeks 24 and 48
Weeks 24 and 48
Percentage of Participants with Symptom Response (Participants who Achieve a >= 50% Reduction from Baseline in the Myeloproliferative Neoplasm Symptom Assessment Form [MPN-SAF] Total Symptom Score [TSS])
Time Frame: Baseline, Weeks 24 and 48
Baseline, Weeks 24 and 48
Duration of Response, as Determined by the Investigator and an IRC Using IWG-MRT Revised Response Criteria or Death from Any Cause During the Study
Time Frame: Baseline up to 28 days after the last dose of study drug (52 weeks)
Baseline up to 28 days after the last dose of study drug (52 weeks)
Percentage of Participants with Improvement from Baseline in Bone Marrow Fibrosis at Weeks 24 and 48, as Determined by the Investigator Using the European Consensus Grading System
Time Frame: Baseline, Weeks 24 and 48
Baseline, Weeks 24 and 48
Percentage of Participants with Improvement from Baseline in Bone Marrow Fibrosis at Weeks 24 and 48, as Determined by Independent Pathology Review Using the European Consensus Grading System
Time Frame: Baseline, Weeks 24 and 48
Baseline, Weeks 24 and 48
Progression-Free Survival
Time Frame: Baseline up to the end of the study (up to 1 year after completing 48 weeks of treatment by the last participant)
Baseline up to the end of the study (up to 1 year after completing 48 weeks of treatment by the last participant)
Percentage of Participants who Achieve a >= 50% Reduction in Fatigue from Baseline to Weeks 24 and 48 as Measured by MPN-SAF TSS
Time Frame: Baseline, Weeks 24 and 48
Baseline, Weeks 24 and 48
Percentage of Participants who Achieve a >= 50% Reduction in Other Symptom and Impact Item Scores from Baseline to Weeks 24 and 48, as Measured by the MPN-SAF
Time Frame: Baseline, Weeks 24 and 48
Baseline, Weeks 24 and 48
Percentage of Participants who Achieve a Meaningful Improvement on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 Scale Scores from Baseline to Weeks 24 and 48
Time Frame: Baseline, Weeks 24 and 48
Meaningful improvement is defined as a 10-point change.
Baseline, Weeks 24 and 48
Overall Survival
Time Frame: Baseline up to the end of the study (up to 1 year after completing 48 weeks treatment by the last participant)
Baseline up to the end of the study (up to 1 year after completing 48 weeks treatment by the last participant)
Percentage of Participants with Adverse Events (AEs)
Time Frame: Baseline up to Month 48
Baseline up to Month 48

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Hoffmann-La Roche

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.

General Publications

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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 25, 2016

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 29, 2017

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 12, 2017

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 29, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 29, 2015

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 1, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 11, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 4, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • WO29806
  • 2015-001620-33 (EudraCT Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

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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