Clinical Trial: NCT02593760 - My Cancer Genome

NCT02593760

Description:

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.

Related Conditions:

Myelofibrosis Transformation in Essential Thrombocythemia
Polycythemia Vera, Post-Polycythemic Myelofibrosis Phase
Primary Myelofibrosis

Recruiting Status:

Completed

Phase:

Phase 1

URL:

https://clinicaltrials.gov/show/NCT02593760

Trial Eligibility

Document

Title

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

Clinical Trial IDs

ORG STUDY ID: WO29806
SECONDARY ID: 2015-001620-33
NCT ID: NCT02593760

Conditions

Myelofibrosis

Interventions

Drug	Synonyms	Arms
Ruxolitinib		Placebo + Ruxolitinib
Vismodegib	Erivedge	Vismodegib + Ruxolitinib

Purpose

Trial Arms

Name	Type	Description	Interventions
Placebo + Ruxolitinib	Active Comparator	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.	Ruxolitinib
Vismodegib + Ruxolitinib	Experimental	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.	Ruxolitinib Vismodegib

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

Maximum Eligible Age:	N/A
Minimum Eligible Age:	18 Years
Eligible Gender:	All
Healthy Volunteers:	No

Primary Outcome Measures

Measure:	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
Safety Issue:
Description:	Determined by an Independent Review Committee (IRC) Using International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) Revised Response Criteria

Secondary Outcome Measures

Measure:	Plasma Vismodegib Concentration at Steady State
Time Frame:	Predose (0 hour) on Weeks 6, 12, 24, 36, and 48
Safety Issue:
Description:

Measure:	Unbound Vismodegib Concentration at Steady State
Time Frame:	Predose (0 hour) on Weeks 6, 12, 24, 36, and 48
Safety Issue:
Description:

Measure:	Alpha 1-Acid Glycoprotein Concentration at Steady State
Time Frame:	Predose (0 hour) on Weeks 6, 12, 24, 36, and 48
Safety Issue:
Description:

Measure:	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
Safety Issue:
Description:

Measure:	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
Safety Issue:
Description:

Measure:	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
Safety Issue:
Description:

Measure:	Percentage of Participants with CR and PR, as Determined by an Investigator at Weeks 24 and 48
Time Frame:	Weeks 24 and 48
Safety Issue:
Description:

Measure:	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
Safety Issue:
Description:

Measure:	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
Safety Issue:
Description:

Measure:	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
Safety Issue:
Description:

Measure:	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
Safety Issue:
Description:

Measure:	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)
Safety Issue:
Description:

Measure:	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
Safety Issue:
Description:

Measure:	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
Safety Issue:
Description:

Measure:	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)
Safety Issue:
Description:

Measure:	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
Safety Issue:
Description:

Measure:	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
Safety Issue:
Description:

Measure:	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
Safety Issue:
Description:	Meaningful improvement is defined as a 10-point change.

Measure:	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)
Safety Issue:
Description:

Measure:	Percentage of Participants with Adverse Events (AEs)
Time Frame:	Baseline up to Month 48
Safety Issue:
Description:

Details

Phase:	Phase 1
Primary Purpose:	Interventional
Overall Status:	Completed
Lead Sponsor:	Hoffmann-La Roche

Last Updated

May 11, 2018

Clinical Trials /

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