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

This study is currently recruiting participants.
Verified August 2017 by Hoffmann-La Roche
Sponsor:
ClinicalTrials.gov Identifier:
NCT02593760
First Posted: November 2, 2015
Last Update Posted: August 22, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Hoffmann-La Roche
  Purpose
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.

Condition Intervention Phase
Myelofibrosis Other: Placebo Drug: Ruxolitinib Drug: Vismodegib Phase 1 Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • 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

  • 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 ]

Secondary Outcome Measures:
  • Plasma Vismodegib Concentration at Steady State [ Time Frame: 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 ]
  • Alpha 1-Acid Glycoprotein Concentration at Steady State [ Time Frame: 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 ]
  • 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 ]
  • 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 ]
  • Percentage of Participants with CR and PR, as Determined by an Investigator at Weeks 24 and 48 [ Time Frame: 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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) ]
  • 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 ]
  • 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 ]
  • 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) ]
  • 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 ]
  • 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 ]
  • 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.

  • 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) ]
  • Percentage of Participants with Adverse Events (AEs) [ Time Frame: Baseline up to Month 48 ]

Estimated Enrollment: 104
Actual Study Start Date: January 25, 2016
Estimated Study Completion Date: December 13, 2019
Estimated Primary Completion Date: December 13, 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Erivedge

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02593760


Contacts
Contact: Reference Study ID Number: WO29806 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. and Canada) global-roche-genentech-trials@gene.com

Locations
United States, Alabama
University of Alabama at Birmingham Withdrawn
Birmingham, Alabama, United States, 35294-3300
United States, California
Uni of Southern California; Norris Comprehensive Cancer Ctr Withdrawn
Los Angeles, California, United States, 90033
United States, Colorado
Kaiser Permanente - Franklin Withdrawn
Denver, Colorado, United States, 80205
United States, Florida
Florida Cancer Specialists-Broadway, Fort Myers Active, not recruiting
Fort Myers, Florida, United States, 33908
Florida Cancer Specialist, North Region Recruiting
Saint Petersburg, Florida, United States, 33705
Florida Cancer Specialists Active, not recruiting
West Palm Beach, Florida, United States, 33401
United States, Michigan
University of Michigan Withdrawn
Ann Arbor, Michigan, United States, 48109-0934
United States, New Mexico
New Mexico Cancer Care Alliance Withdrawn
Albuquerque, New Mexico, United States, 87106
United States, Ohio
Oncology Hematology Care Inc Terminated
Cincinnati, Ohio, United States, 45242
United States, Pennsylvania
University of Pennsylvania Health System; Cancer Center Withdrawn
Philadelphia, Pennsylvania, United States, 19104
United States, Tennessee
Sarah Cannon Research Institute Active, not recruiting
Nashville, Tennessee, United States, 37203
United States, Texas
Uni of Texas - Md Anderson Cancer Center; Dept of Leukemia Active, not recruiting
Houston, Texas, United States, 77030
Canada, Alberta
Tom Baker Cancer Centre-Calgary; Clinical Research Unit Active, not recruiting
Calgary, Alberta, Canada, T2N 4N2
Canada, Nova Scotia
QEII HSC; Oncology Completed
Halifax, Nova Scotia, Canada, B3H 2Y9
Canada, Quebec
Centre Hospitalier De L'Universite De Montreal, Hopital Notre-Dame Recruiting
Montreal, Quebec, Canada, H2L 4M1
Germany
Uniklinik RWTH Aachen; Med. Klinik IV; Klinik für Hämatologie, Onkologie, Hämostaseologie und Stammz Active, not recruiting
Aachen, Germany, 52074
Campus Virchow-Klinikum Charité Centrum 14; Medizinische Klinik m.S. Hämatologie u. Onkologie Terminated
Berlin, Germany, 13353
Italy
Ospedale Di Circolo E Fondazione Macchi; Ematologia Not yet recruiting
Varese, Lombardia, Italy, 21100
A.O.U. Citta' Della Salute E Della Scienza-P.O. Molinette;S.C. Ematologia Recruiting
Torino, Piemonte, Italy, 10126
Az. Osp. Di Careggi; Divisione Di Ematologia Recruiting
Firenze, Toscana, Italy, 50135
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT02593760     History of Changes
Other Study ID Numbers: WO29806
2015-001620-33 ( EudraCT Number )
First Submitted: October 29, 2015
First Posted: November 2, 2015
Last Update Posted: August 22, 2017
Last Verified: August 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Primary Myelofibrosis
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases