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

Last updated on October 18, 2019

FOR MORE INFORMATION
Study Location
Mayo Clinic Building - Phoenix
Phoenix, Arizona, 85054 United States
Contact
1-800-718-1021
Eligibility criteria
Condition
The disease, disorder, syndrome, illness, or injury that is being studied.
Primary Myelofibrosis; Post-polycythemia Vera Myelofibrosis; Post-essential Thrombocythemia Myelofibrosis
Sex
Females and Males
Age
Pediatric Trials: 0-17 Years
Adult Trials: 18+ Years
18 + years
Inclusion criteria
The factors, or reasons, that allow a person to participate in a clinical study.
Show details

- 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
The factors, or reasons, that prevent a person from participating in a clinical study.
Show details

- 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.

NCT02226172
Pfizer
Terminated
Single-Agent Glasdegib In Patients With Myelofibrosis Previously Treated With Ruxolitinib

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Descriptive Information
Brief Title  ICMJE Single-Agent Glasdegib In Patients With Myelofibrosis Previously Treated With Ruxolitinib
Official Title  ICMJE A Phase 2, Double-blind, Randomized Safety And Efficacy Study Of Glasdegib (Pf-04449913) Versus Placebo In Patients With Myelofibrosis Previously Treated With Ruxolitinib
Brief SummaryA 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.
Detailed DescriptionNot Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Primary Myelofibrosis; Post-polycythemia Vera Myelofibrosis; Post-essential Thrombocythemia Myelofibrosis
Intervention  ICMJE
  • Drug: Glasdegib (PF-04449913)
    Oral daily dose of glasdegib (PF-04449913) 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.
Study Arms  ICMJE
  • Experimental: Arm A
    Oral daily dose of glasdegib (PF-04449913) 100 mg tablet in a continuous regimen of 28-day cycles.
    Intervention: Drug: Glasdegib (PF-04449913)
  • Placebo Comparator: Arm B
    Oral daily dose of placebo 100 mg tablet in a continuous regimen of 28-day cycles.
    Intervention: Drug: Placebo
Publications *Not Provided


*   Includes publications given by the data provider as well as publications
identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: March 30, 2018)
21
Original Estimated Enrollment  ICMJE
 (submitted: August 25, 2014)
222
Actual Study Completion Date  ICMJE January 31, 2018
Actual Primary Completion DateDecember 14, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study:All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Japan,   United States
Removed Location CountriesUnited Kingdom
 
Administrative Information
NCT Number  ICMJE NCT02226172
Other Study ID Numbers  ICMJE B1371013
SMOI ( Other Identifier: Alias Study Number )
2014-000933-21 ( EudraCT Number )
2014-001048-40 ( EudraCT Number )
Has Data Monitoring CommitteeYes
U.S. FDA-regulated ProductNot Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible PartyPfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director:Pfizer CT.gov Call CenterPfizer
PRS AccountPfizer
Verification DateDecember 2018

ICMJE     Data element required by the

International Committee of Medical Journal Editors
and the
World Health Organization ICTRP

FOR MORE INFORMATION

Contact a representative by phone, email, or visiting the study website. Please see the references below:

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