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

This study is currently recruiting participants.
See Contacts and Locations
Verified November 2016 by Hoffmann-La Roche
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT02593760
First received: October 29, 2015
Last updated: November 1, 2016
Last verified: November 2016
  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 1b portion of the study will be started with 6-week safety run-in period with 10 participants who will receive vismodegib (150 milligrams [mg] orally [PO] once daily [QD]) + ruxolitinib (PO twice daily [BID]) for the assessment of acute safety events associated with this combined therapy. After getting confirmation about the safety and toxicity of this combination, the Phase 3 randomization portion of the study will begin during which approximately 84 participants will randomly assign in 1:1 ratio to receive either vismodegib (150 mg PO QD) plus ruxolitinib (PO BID) or placebo (PO QD) plus ruxolitinib (PO BID) for up to 48 weeks or until withdrawal or discontinuation, whichever occurs first.

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 Blind (Participant, Investigator)
Primary Purpose: Treatment

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 equal to (>=) 35% reduction in spleen volume at Week 24, as determined by an IRC using IWG-MRT revised response criteria [ Time Frame: Week 24 ]
  • Percentage of participants with complete response (CR) and partial response (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, Weeks 6, 12, 24, 36, and 48 ]
  • Percentage of participants who achieve a >=35% reduction in spleen volume, as determined by an IRC using IWG-MRT revised response criteria at Week 48 and by an Investigator at Weeks 24 and 48 [ Time Frame: 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 and by an Investigator at Weeks 24 and 48 [ Time Frame: Weeks 24 and 48 ]
  • Percentage of Participants with objective response rate (CR, PR and clinical improvement) at Weeks 24 and 48, as determined by an IRC and 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 rate (participants who achieve a >=50% reduction in the Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score [MPN-SAF TSS]) [ Time Frame: Baseline, Weeks 24 and 48 ]
  • Duration of response, determined by the Investigator and an IRC using IWG-MRT revised response criteria or death from any cause during the study [ Time Frame: 28 days after the last dose of study drug (52 weeks) ]
  • Percentage of participants with improvement in bone marrow fibrosis at Weeks 24 and 48, as determined by the Investigator and independent pathology review using the European consensus grading system [ Time Frame: Weeks 24 and 48 ]
  • Progression free survival [ Time Frame: 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 \nand 48 [ 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 achieved a meaningful improvement on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) scale scores from baseline to Weeks 24 and 48 [ Time Frame: Baseline, Weeks 24 and 48 ]
  • Overall survival [ Time Frame: up to the end of the study (up to 1 year after completing 48 weeks treatment by the last participant) ]

Estimated Enrollment: 20
Study Start Date: January 2016
Estimated Study Completion Date: November 2019
Estimated Primary Completion Date: November 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

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 International Working Group- Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) Dynamic International Prognostic Scoring System (DIPSS)
  • Participants aged greater than or equal to (>=) 18 years
  • 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 (ECOG) Performance Status of 0 to 2
  • Adequate hepatic and renal function as assessed by:

Total bilirubin less than or equal to (<=) 2.0*upper limit of normal (ULN), unless resulting from hemolysis and Gilbert's Syndrome Aspartate transaminase and alanine transaminase <=2.5*ULN (<=5*ULN if liver is involved by extramedullary hematopoiesis as determined by investigator) Serum creatinine <=1.5*ULN and creatinine clearance greater than (>) 30 milliliters per minute (mL/min)

Exclusion Criteria:

  • Prior treatment with a Hedgehog or Janus kinase (JAK) pathway inhibitor
  • Treatment with strong cytochrome P450 (CYP) 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 as follows:

Absolute neutrophil count of <=1000/microliters (mcL) Platelet count of <100,000/mcL without the assistance of growth factors, thrombopoietic factors, or platelet transfusions

  • Participants with any history of platelet counts of <50,000/mccL or ANC of <500/mL, except during treatment for myeloproliferative neoplasm (MPN) or treatment with cytotoxic therapy for any other reason
  • Planned allogeneic bone marrow transplant during the study
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02593760

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

Locations
United States, Florida
Recruiting
Fort Myers, Florida, United States, 33908
Recruiting
St Petersburg, Florida, United States, 33705
Recruiting
West Palm Beach, Florida, United States, 33401
United States, Ohio
Terminated
Cincinnati, Ohio, United States, 45242
United States, Tennessee
Active, not recruiting
Nashville, Tennessee, United States, 37203
United States, Texas
Recruiting
Houston, Texas, United States, 77030
Canada, Alberta
Recruiting
Calgary, Alberta, Canada, T2N 4N2
Canada, Manitoba
Not yet recruiting
Winnipeg, Manitoba, Canada, R3E 0V9
Canada, Nova Scotia
Recruiting
Halifax, Nova Scotia, Canada, B3H 2Y9
Canada, Quebec
Recruiting
Montreal, Quebec, Canada, H2L 4M1
Germany
Recruiting
Aachen, Germany, 52074
Recruiting
Berlin, Germany, 13353
Italy
Not yet recruiting
Varese, Lombardia, Italy, 21100
Recruiting
Torino, Piemonte, Italy, 10126
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 )
Study First Received: October 29, 2015
Last Updated: November 1, 2016

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

ClinicalTrials.gov processed this record on June 22, 2017