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

This study is currently recruiting participants.
Verified October 2017 by Pfizer
Sponsor:
ClinicalTrials.gov Identifier:
NCT02226172
First Posted: August 27, 2014
Last Update Posted: October 31, 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):
Pfizer
  Purpose
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.

Condition Intervention Phase
Primary Myelofibrosis; Post-polycythemia Vera Myelofibrosis; Post-essential Thrombocythemia Myelofibrosis Drug: Glasdegib (PF-04449913) Drug: Placebo Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 2, Double-blind, Randomized Safety And Efficacy Study Of Pf 04449913 Versus Placebo With Defined Best Supportive Therapy Allowed In Both Arms In Patients With Myelofibrosis Previously Treated With One Or More Janus Kinase Inhibitors

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Proportion of patients achieving spleen volume reduction =>35% from baseline to Week 24 as measured by MRI/CT. [ Time Frame: 24 weeks ]

Secondary Outcome Measures:
  • Proportion of patients achieving =>50% reduction in total symptom score from baseline through Week 24, as measured by the Myeloproliferative neoplasm symptom assessment diary. [ Time Frame: 24 weeks ]
  • Proportion of patients with improvement in peripheral blood counts, as defined by the Revised IWG-MRT Response Criteria. [ Time Frame: 24 weeks ]

Estimated Enrollment: 222
Actual Study Start Date: October 2014
Estimated Study Completion Date: December 2017
Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A
Oral daily dose of glasdegib (PF-04449913) 100 mg tablet in a continuous regimen of 28-day cycles.
Drug: Glasdegib (PF-04449913)
Oral daily dose of glasdegib (PF-04449913) 100 mg tablet in a continuous regimen of 28-day cycles.
Placebo Comparator: Arm B
Oral daily dose of placebo 100 mg tablet in a continuous regimen of 28-day cycles.
Drug: Placebo
Oral daily dose of placebo 100 mg tablet in a continuous regimen of 28-day cycles.

  Eligibility

Information from the National Library of Medicine

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

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);
    4. Serum amylase or lipase <1.5 x ULN;
    5. Aspartate aminotransferase and alanine aminotransferase values 3.0 x ULN (or 5x ULN in the case of patients with MF accompanied by hepatic extramedullary hematopoiesis, as manifested by any degree of hepatomegaly).
    6. Total bilirubin values <1.5 x ULN unless the bilirubin is principally unconjugated (in the context of hemolysis) or there is documented Gilbert's disease.
    7. Serum electrolyte values < Grade 2 (sodium, potassium, calcium, phosphorous and magnesium), per CTCAE v.4.03.
  • Recovery to Grade 1 from all clinically significant adverse events related to prior MF therapy, including transplant-related toxicities.
  • More than 2 months out from allogenic hematopoietic stem cell transplant prior to randomization.
  • Must be able to undergo MRI of abdomen (spleen and liver). Patients who are contra indicated for MRI may be enrolled and evaluated by CT scan at the discretion of the Sponsor.
  • 18 years of age.
  • Male subjects able to father children and female patients of childbearing potential and at risk for pregnancy must agree to use two highly effective methods of contraception throughout the study and for 90 days after the last dose of assigned treatment.

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.
  • Currently active malignancy (other than MF). Prior malignancies are allowed so long as there is no evidence of disease recurrence within the last 2 years (with the exception of fully excised, non-complicated basal cell carcinoma which can have been active within the prior 2 years, and certain localized, non-invasive fully excised skin, cervical, breast, prostate or bladder tumors).
  • Prior history of chronic liver disease (eg, chronic alcoholic liver disease, autoimmune hepatitis, sclerosing cholangitis, primary biliary cirrhosis, hemachromatosis, non-alcoholic steatohepatitis [NASH]).
  • Active, uncontrolled bacterial, fungal or viral infection, including hepatitis B, hepatitis C, known human immunodeficiency virus or acquired immunodeficiency syndrome related illness.
  • Active graft versus host disease (GVHD) with other than grade 1 skin involvement or GVHD requiring immunosuppressive treatment.
  • Uncontrolled disseminated intravascular coagulation.
  • Current (including their administration within 3 days prior to study entry) use or anticipated need for food or drugs that are strong CYP3A4 inhibitors.
  • Current use or anticipated requirement for drugs that are known strong CYP3A4/5 inducers.
  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): NCT02226172


Contacts
Contact: Pfizer CT.gov Call Center 1-800-718-1021 ClinicalTrials.gov_Inquiries@pfizer.com

Locations
United States, Arizona
Mayo Clinic Building, Phoenix Active, not recruiting
Phoenix, Arizona, United States, 85054
Mayo Clinic Hospital Active, not recruiting
Phoenix, Arizona, United States, 85054
Mayo Clinic Building - Phoenix Active, not recruiting
Phoenix, Arizona, United States, 85084
Mayo Clinic Active, not recruiting
Scottsdale, Arizona, United States, 85259
United States, California
UC San Diego Moores Cancer Center - Investigational Drug Services Active, not recruiting
La Jolla, California, United States, 92037-0845
UCSD Medical Center Clinical Laboratory - La Jolla Active, not recruiting
La Jolla, California, United States, 92037
University of California San Diego (UCSD) Moores Cancer Center Active, not recruiting
La Jolla, California, United States, 92093-0698
UC San Diego Medical Center- Hillcrest Active, not recruiting
San Diego, California, United States, 92103
United States, Michigan
University of Michigan Active, not recruiting
Ann Arbor, Michigan, United States, 48109
United States, New York
Weill Cornell Medical College - New York-Presbyterian Hospital Active, not recruiting
New York, New York, United States, 10021
Weill Cornell Medical College-New York Presbyterian Hospital Active, not recruiting
New York, New York, United States, 10021
Herbert Irving Comprehensive Cancer Center-Columbia University Medical Center Active, not recruiting
New York, New York, United States, 10032
New York - Presbyterian Hospital Active, not recruiting
New York, New York, United States, 10065
Weill Cornell Medical College-New York Presbyterian Hospital Active, not recruiting
New York, New York, United States, 10065
Weill Cornell Medical College Active, not recruiting
New York, New York, United States, 10065
United States, Ohio
Cleveland Clinic - Taussig Cancer Institute Recruiting
Cleveland, Ohio, United States, 44195
United States, Utah
Huntsman Cancer Institute-University of Utah Active, not recruiting
Salt Lake City, Utah, United States, 84112
University of Utah, Huntsman Cancer Hospital Active, not recruiting
Salt Lake City, Utah, United States, 84112
United States, Wisconsin
Froedtert Hospital and the Medical College of Wisconsin Terminated
Milwaukee, Wisconsin, United States, 53266
Japan
Kobe University Hospital Active, not recruiting
Kobe, Hyogo, Japan, 6500017
Juntendo University Hospital Active, not recruiting
Bunkyo-ku, Tokyo, Japan, 113-8431
Osaka University Hospital Terminated
Osaka, Japan, 565-0871
Tokyo Medical University Hospital Recruiting
Tokyo, Japan, 160-0023
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT02226172     History of Changes
Other Study ID Numbers: B1371013
SMOI ( Other Identifier: Alias Study Number )
2014-000933-21 ( EudraCT Number )
2014-001048-40 ( EudraCT Number )
First Submitted: August 25, 2014
First Posted: August 27, 2014
Last Update Posted: October 31, 2017
Last Verified: October 2017

Keywords provided by Pfizer:
Primary myelofibrosis
Secondary myelofibrosis
PMF
PET-MF
PPV-MF
Ruxolitinib resistant or intolerant
previously treated myelofibrosis
smoothened inhibitor
oral
single agent.

Additional relevant MeSH terms:
Primary Myelofibrosis
Polycythemia
Polycythemia Vera
Thrombocytosis
Thrombocythemia, Essential
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Bone Marrow Neoplasms
Hematologic Neoplasms
Neoplasms by Site
Neoplasms
Blood Platelet Disorders
Blood Coagulation Disorders
Hemorrhagic Disorders