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

NCT ID: NCT02593760

Last Updated: 2018-05-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-01-25
• Study Completion Date: 2017-07-12

Brief Summary

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.

Conditions

Myelofibrosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Placebo

Intervention Type: OTHER

Placebo will be administered PO QD for up to 48 weeks.

Ruxolitinib

Intervention Type: DRUG

Ruxolitinib will be administered PO BID at a starting dose depending on the participants's baseline platelet count for up to 48 weeks.

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.

Group Type: EXPERIMENTAL

Ruxolitinib

Intervention Type: DRUG

Ruxolitinib will be administered PO BID at a starting dose depending on the participants's baseline platelet count for up to 48 weeks.

Vismodegib

Intervention Type: DRUG

Vismodegib will be administered at a dose of 150 mg PO QD for up to 48 weeks.

Interventions

Placebo

Placebo will be administered PO QD for up to 48 weeks.

Intervention Type: OTHER

Ruxolitinib

Ruxolitinib will be administered PO BID at a starting dose depending on the participants's baseline platelet count for up to 48 weeks.

Intervention Type: DRUG

Vismodegib

Vismodegib will be administered at a dose of 150 mg PO QD for up to 48 weeks.

Intervention Type: DRUG

Other Intervention Names

Erivedge

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

Florida Cancer Specialists-Broadway, Fort Myers

Fort Myers, Florida, United States

Florida Cancer Specialist, North Region

St. Petersburg, Florida, United States

Florida Cancer Specialists

West Palm Beach, Florida, United States

Oncology Hematology Care Inc

Cincinnati, Ohio, United States

Sarah Cannon Research Institute

Nashville, Tennessee, United States

Uni of Texas - Md Anderson Cancer Center; Dept of Leukemia

Houston, Texas, United States

Tom Baker Cancer Centre-Calgary; Clinical Research Unit

Calgary, Alberta, Canada

Queen Elizabeth II Health Sciences Centre; Oncology

Halifax, Nova Scotia, Canada

Centre Hospitalier De L'Universite De Montreal, Hopital Notre-Dame

Montreal, Quebec, Canada

Uniklinik RWTH Aachen; Med. Klinik IV; Klinik für Hämatologie, Onkologie, Hämostaseologie und Stammz

Aachen, , Germany

Campus Virchow-Klinikum Charité Centrum 14; Medizinische Klinik m.S. Hämatologie u. Onkologie

Berlin, , Germany

A.O.U. Citta' Della Salute E Della Scienza-P.O. Molinette;S.C. Ematologia

Turin, Piedmont, Italy

Az. Osp. Di Careggi; Divisione Di Ematologia

Florence, Tuscany, Italy

Countries

United States; Canada; Germany; Italy

References

Couban S, Benevolo G, Donnellan W, Cultrera J, Koschmieder S, Verstovsek S, Hooper G, Hertig C, Tandon M, Dimier N, Malhi V, Passamonti F. A phase Ib study to assess the efficacy and safety of vismodegib in combination with ruxolitinib in patients with intermediate- or high-risk myelofibrosis. J Hematol Oncol. 2018 Sep 24;11(1):122. doi: 10.1186/s13045-018-0661-x.

Reference Type: DERIVED

PMID: 30249277 (View on PubMed)

Other Identifiers

2015-001620-33

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

WO29806

Identifier Type: -

Identifier Source: org_study_id