A Combination Study of PF-04449913 (Glasdegib) and Azacitidine In Untreated MDS, AML and CMML Patients

NCT ID: NCT02367456

Last Updated: 2024-01-19

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

73 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-04-28

Study Completion Date

2022-03-07

Brief Summary

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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.

Detailed Description

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Conditions

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Myelodysplastic Syndrome Acute Myeloid Leukemia Chronic Myelomonocytic Leukemia

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm A

MDS patients: PF-04449913 (Glasdegib) 100 mg + Azacitidine 75 mg/m2

Group Type EXPERIMENTAL

PF-04449913 (Glasdegib)

Intervention Type DRUG

Daily dose of PF-04449913 100mg tablet in a continuous regimen of 28 day cycles

Azacitidine

Intervention Type DRUG

75mg/m2 on Days 1-7 (+/- 3 days for each dose) of a 28 day cycle

Arm B

AML patients: PF-04449913 (Glasdegib) 100 mg + Azacitidine 75 mg/m2

Group Type EXPERIMENTAL

PF-04449913 (Glasdegib)

Intervention Type DRUG

Daily dose of PF-04449913 100mg tablet in a continuous regimen of 28 day cycles

Azacitidine

Intervention Type DRUG

75mg/m2 on Days 1-7 (+/- 3 days for each dose) of a 28 day cycle

Interventions

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PF-04449913 (Glasdegib)

Daily dose of PF-04449913 100mg tablet in a continuous regimen of 28 day cycles

Intervention Type DRUG

Azacitidine

75mg/m2 on Days 1-7 (+/- 3 days for each dose) of a 28 day cycle

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Patients must have previously untreated MDS, AML, or CMML 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 (IPSS-R).
* 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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Pfizer

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Pfizer CT.gov Call Center

Role: STUDY_DIRECTOR

Pfizer

Locations

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University of Alabama at Birmingham the Kirklin Clinic

Birmingham, Alabama, United States

Site Status

University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status

UC San Diego Moores Cancer Center

La Jolla, California, United States

Site Status

Smilow Cancer Center at Yale New Haven Hospital

New Haven, Connecticut, United States

Site Status

The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States

Site Status

Roswell Park Cancer Institute

Buffalo, New York, United States

Site Status

Stony Brook University Hospital Cancer Center

Stony Brook, New York, United States

Site Status

Stony Brook University

Stony Brook, New York, United States

Site Status

Montefiore Einstein Center for Cancer

The Bronx, New York, United States

Site Status

Montefiore Medical Center

The Bronx, New York, United States

Site Status

Duke University Health System: Adult Bone Marrow Transplant Clinic

Durham, North Carolina, United States

Site Status

Duke University Health System, Duke University Hospital

Durham, North Carolina, United States

Site Status

Duke University Health System

Durham, North Carolina, United States

Site Status

Investigational Chemotherapy Service

Durham, North Carolina, United States

Site Status

Cleveland Clinic Taussig Cancer Center

Cleveland, Ohio, United States

Site Status

Henry-Joyce Cancer Center

Nashville, Tennessee, United States

Site Status

Vanderbilt - Ingram Cancer Center

Nashville, Tennessee, United States

Site Status

Huntsman Cancer Hospital

Salt Lake City, Utah, United States

Site Status

Huntsman Cancer Institute

Salt Lake City, Utah, United States

Site Status

Seattle Cancer Care Alliance (SCCA)

Seattle, Washington, United States

Site Status

University of Washington Medical Center (UWMC)

Seattle, Washington, United States

Site Status

Ziekenhuis Netwerk Antwerpen - Campus Stuivenberg

Antwerp, , Belgium

Site Status

UZ Leuven

Leuven, , Belgium

Site Status

Tom Baker Cancer Center

Calgary, Alberta, Canada

Site Status

University Of Alberta Hospital

Edmonton, Alberta, Canada

Site Status

CHU d'Amiens-Picardie - Hopital SUD

Amiens, , France

Site Status

Hopital Saint-Louis (AP-HP) - Service Hematologie Senior

Paris, , France

Site Status

Hospices Civils de Lyon - Hopital Lyon Sud- Hematologie

Pierre-Bénite, , France

Site Status

CHU de Tours-Hopital Bretonneau-Centre Regional de cancerologie Henry Kaplan

Tours, , France

Site Status

Staedtisches Klinikum Braunschweig gGmbH

Braunschweig, , Germany

Site Status

King's College Hospital

London, , United Kingdom

Site Status

The Newcastle Hospitals NHS Foundation Trust

Newcastle upon Tyne, , United Kingdom

Site Status

Oxford University Hospitals NHS Foundation Trust

Oxford, , United Kingdom

Site Status

Countries

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United States Belgium Canada France Germany United Kingdom

References

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Sekeres MA, Schuster M, Joris M, Krauter J, Maertens J, Breems D, Gyan E, Kovacsovics T, Verma A, Vyas P, Wang ES, Ching K, O'Brien T, Gallo Stampino C, Ma WW, Kudla A, Chan G, Zeidan AM. A phase 1b study of glasdegib + azacitidine in patients with untreated acute myeloid leukemia and higher-risk myelodysplastic syndromes. Ann Hematol. 2022 Aug;101(8):1689-1701. doi: 10.1007/s00277-022-04853-4. Epub 2022 Apr 30.

Reference Type DERIVED
PMID: 35488900 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

Other Identifiers

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2014-001345-24

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

BRIGHT MDS&AML1012

Identifier Type: OTHER

Identifier Source: secondary_id

B1371012

Identifier Type: -

Identifier Source: org_study_id

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