- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02593760
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
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
10
Phase
- 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
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Alberta
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Calgary, Alberta, Canada, T2N 4N2
- Tom Baker Cancer Centre-Calgary; Clinical Research Unit
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Nova Scotia
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Halifax, Nova Scotia, Canada, B3H 2Y9
- Queen Elizabeth II Health Sciences Centre; Oncology
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Quebec
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Montreal, Quebec, Canada, H2L 4M1
- Centre Hospitalier De L'Universite De Montreal, Hopital Notre-Dame
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Aachen, Germany, 52074
- Uniklinik RWTH Aachen; Med. Klinik IV; Klinik für Hämatologie, Onkologie, Hämostaseologie und Stammz
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Berlin, Germany, 13353
- Campus Virchow-Klinikum Charité Centrum 14; Medizinische Klinik m.S. Hämatologie u. Onkologie
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Piemonte
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Torino, Piemonte, Italy, 10126
- A.O.U. Citta' Della Salute E Della Scienza-P.O. Molinette;S.C. Ematologia
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Toscana
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Firenze, Toscana, Italy, 50135
- Az. Osp. Di Careggi; Divisione Di Ematologia
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Florida
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Fort Myers, Florida, United States, 33908
- Florida Cancer Specialists-Broadway, Fort Myers
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Saint Petersburg, Florida, United States, 33705
- Florida Cancer Specialist, North Region
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West Palm Beach, Florida, United States, 33401
- Florida Cancer Specialists
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Ohio
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Cincinnati, Ohio, United States, 45242
- Oncology Hematology Care Inc
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Tennessee
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Nashville, Tennessee, United States, 37203
- Sarah Cannon Research Institute
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Texas
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Houston, Texas, United States, 77030
- Uni of Texas - Md Anderson Cancer Center; Dept of Leukemia
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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 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 |
Intervention / Treatment |
---|---|
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.
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Placebo will be administered PO QD for up to 48 weeks.
Ruxolitinib will be administered PO BID at a starting dose depending on the participants's baseline platelet count for up to 48 weeks.
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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.
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Ruxolitinib will be administered PO BID at a starting dose depending on the participants's baseline platelet count for up to 48 weeks.
Vismodegib will be administered at a dose of 150 mg PO QD for up to 48 weeks.
Other Names:
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What is the study measuring?
Primary Outcome Measures
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
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Determined by an Independent Review Committee (IRC) Using International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) Revised Response Criteria
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Week 24
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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
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Week 24
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Secondary Outcome Measures
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
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Predose (0 hour) on Weeks 6, 12, 24, 36, and 48
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Unbound Vismodegib Concentration at Steady State
Time Frame: Predose (0 hour) on Weeks 6, 12, 24, 36, and 48
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Predose (0 hour) on Weeks 6, 12, 24, 36, and 48
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Alpha 1-Acid Glycoprotein Concentration at Steady State
Time Frame: Predose (0 hour) on Weeks 6, 12, 24, 36, and 48
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Predose (0 hour) on Weeks 6, 12, 24, 36, and 48
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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
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Baseline, Week 48
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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
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Baseline, Weeks 24 and 48
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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
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Week 48
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Percentage of Participants with CR and PR, as Determined by an Investigator at Weeks 24 and 48
Time Frame: Weeks 24 and 48
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Weeks 24 and 48
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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
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Weeks 24 and 48
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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
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Weeks 24 and 48
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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
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Weeks 24 and 48
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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
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Baseline, Weeks 24 and 48
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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)
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Baseline up to 28 days after the last dose of study drug (52 weeks)
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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
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Baseline, Weeks 24 and 48
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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
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Baseline, Weeks 24 and 48
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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)
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Baseline up to the end of the study (up to 1 year after completing 48 weeks of treatment by the last participant)
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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
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Baseline, Weeks 24 and 48
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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
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Baseline, Weeks 24 and 48
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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
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Meaningful improvement is defined as a 10-point change.
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Baseline, Weeks 24 and 48
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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)
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Baseline up to the end of the study (up to 1 year after completing 48 weeks treatment by the last participant)
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Percentage of Participants with Adverse Events (AEs)
Time Frame: Baseline up to Month 48
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Baseline up to Month 48
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
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.
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 25, 2016
Primary Completion (Actual)
March 29, 2017
Study Completion (Actual)
July 12, 2017
Study Registration Dates
First Submitted
October 29, 2015
First Submitted That Met QC Criteria
October 29, 2015
First Posted (Estimate)
November 1, 2015
Study Record Updates
Last Update Posted (Actual)
May 11, 2018
Last Update Submitted That Met QC Criteria
May 4, 2018
Last Verified
May 1, 2018
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID 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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