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Single-Agent Glasdegib In Patients With Myelofibrosis Previously Treated With Ruxolitinib | Clinical Trials | Clareo Health

TERMINATEDPHASE2

Single-Agent Glasdegib In Patients With Myelofibrosis Previously Treated With Ruxolitinib

A Phase 2, Double-blind, Randomized Safety And Efficacy Study Of Glasdegib (Pf-04449913) Versus Placebo In Patients With Myelofibrosis Previously Treated With Ruxolitinib

NCT02226172•Pfizer

View on ClinicalTrials.gov

Summary

A lead-in cohort of \~20 patients with primary or secondary myelofibrosis previously treated with 1 or more Janus kinase inhibitors enrolled to single-agent glasdegib to evaluate safety and tolerability. Following the lead-in, a phase 2, double blind, 2-arm study, randomized 2:1 to oral single-agent glasdegib versus placebo in 201 patients resistant or intolerant to ruxolitinib.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•Diagnosis of primary MF (PMF) or secondary MF (PET-MF and PPV-MF) as per WHO 2008 criteria.
•Lead-in cohort: resistant or intolerant to 1 or more Janus kinase inhibitors (licensed or experimental).
•Randomized cohort: resistant or intolerant to prior ruxolitinib therapy. Documentation by the Investigator that the patient has exhausted available treatment options (eg, resistant or intolerant to hydroxyurea, etc).
•Spleen 5 cm below the inferior left costal margin as measured by manual palpation.
•Active symptomatic MF as defined by the screening MPN-SAD patient-reported instrument requiring a severity score of at least 5 on one symptom, or a severity score of ≥ 3 on at least two of the symptoms (on a 0 to 10 scale).
•Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, 2, or 3.
•Adequate organ function, demonstrated by the following laboratory values:
•1. Absolute Neutrophil Count 75 x 10(9)/L;
•2. Platelet count \>50 x 10(9)/L with no evidence of bleeding and not requiring platelet transfusions;
•3. Serum creatinine \<1.5 x upper limit of normal (ULN) or estimated creatinine clearance 60 mL/min (as calculated using the standard method of the institution);
+9 more criteria

Exclusion Criteria

•Prior treatment with a licensed or experimental smoothened inhibitor.
•Randomized cohort only: Prior treatment with a Janus kinase inhibitor other than ruxolitinib.
•Other anti-cancer therapy up to 14 days prior to enrollment, with the exception of hydroxyurea, which can be given up to 4 days prior to enrollment.
•Splenic irradiation 3 months prior to enrollment.
•History of congenital long QT syndrome, or a baseline \>470 msec QTcF abnormality (average of the triplicate reading).
•Evidence of significant cardiac disease, for example: symptomatic cardiac heart failure (CHF, NYHA class 3), complete bundle branch block, significant atrial or ventricular tachyarrhythmias and any unstable cardiac arrhythmias requiring medication.
•History of myocardial infarction or unstable angina within 6 months prior to enrollment.
•Uncontrolled inflammatory bowel disease, peptic ulcer disease or history of significant gastro intestinal bleeding within 6 months of enrollment.
•Any condition requiring chronic use of moderate/high dose steroids (equivalent to 10 mg QD prednisone).
•Hematopoietic growth factor receptor agonists (eg, erythropoietin (Epo), granulocyte colony stimulating factor, romiplostim, eltrombopag within 28 days of enrollment.
+7 more criteria

Locations (19)

Mayo Clinic Building - Phoenix

Phoenix, Arizona, United States

Mayo Clinic Hospital

Phoenix, Arizona, United States

Mayo Clinic

Scottsdale, Arizona, United States

UC San Diego Moores Cancer Center - Investigational Drug Services

La Jolla, California, United States

UCSD Medical Center Clinical Laboratory - La Jolla

La Jolla, California, United States

University of California San Diego (UCSD) Moores Cancer Center

La Jolla, California, United States

UC San Diego Medical Center- Hillcrest

San Diego, California, United States

University of Michigan

Ann Arbor, Michigan, United States

Weill Cornell Medical College - New York-Presbyterian Hospital

New York, New York, United States

Herbert Irving Comprehensive Cancer Center-Columbia University Medical Center

New York, New York, United States

Key Dates

Start Date

October 6, 2014

Primary Completion Date

December 14, 2016

Completion Date

January 31, 2018

Last Updated

January 17, 2019

Enrollment

ACTUAL participants

Conditions

Primary Myelofibrosis; Post-polycythemia Vera Myelofibrosis; Post-essential Thrombocythemia Myelofibrosis

Interventions

Glasdegib (PF-04449913)

DRUG

Placebo

DRUG