Purpose

This multi center open label Phase 1b study is designed to evaluate the safety, efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) of glasdegib (PF-04449913) when combined with azacitidine in patients with previously untreated Higher Risk Myelodysplastic Syndrome (MDS), Acute Myeloid Leukemia (AML), or Chronic Myelomonocytic Leukemia (CMML). This clinical study includes two components: (a) a safety lead in cohort (LIC) and (b) an expansion phase with an AML cohort and an MDS cohort.

Conditions

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Patients must have previously untreated MDS or AML according to the WHO 2016 classification.
  • MDS patients must have Intermediate (>3 to 4.5 points), High Risk (>4.5 - 6) or Very High Risk (>6 points) disease according to the Revised International Prognostic Scoring System 2012.
  • Clinical indication for treatment with azacitidine for MDS or AML.

Exclusion Criteria

  • Patients with AML who are candidates for standard induction chemotherapy as first line treatment.
  • Patients with known active CNS leukemia.
  • Prior treatment with a smoothened inhibitor (SMOi) and/or hypomethylating agent.

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Arm A
MDS patients: PF-04449913 (Glasdegib) 100 mg + Azacitidine 75 mg/m2
  • Drug: PF-04449913 (Glasdegib)
    Daily dose of PF-04449913 100mg tablet in a continuous regimen of 28 day cycles
  • Drug: Azacitidine
    75mg/m2 on Days 1-7 (+/- 3 days for each dose) of a 28 day cycle
Experimental
Arm B
AML patients: PF-04449913 (Glasdegib) 100 mg + Azacitidine 75 mg/m2
  • Drug: PF-04449913 (Glasdegib)
    Daily dose of PF-04449913 100mg tablet in a continuous regimen of 28 day cycles
  • Drug: Azacitidine
    75mg/m2 on Days 1-7 (+/- 3 days for each dose) of a 28 day cycle

Recruiting Locations

Montefiore Medical Center
Bronx, New York 10467

Montefiore Einstein Center for Cancer
Bronx, New York 10461

More Details

NCT ID
NCT02367456
Status
Recruiting
Sponsor
Pfizer

Study Contact

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

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.