Continuation Study of B1371019(NCT03416179) and B1371012(NCT02367456) Evaluating Azacitidine With Or Without Glasdegib In Patients With Previously Untreated AML, MDS or CMML

A MULTI-CENTER CONTINUATION STUDY EVALUATING AZACITIDINE WITH OR WITHOUT GLASDEGIB (PF-04449913) IN PATIENTS WITH PREVIOUSLY UNTREATED ACUTE MYELOID LEUKEMIA, MYELODYSPLASTIC SYNDROME OR CHRONIC MYELOMONOCYTIC LEUKEMIA

An open-label study available to all eligible participants from Study B1371019 and participants originating from Study B1371012 continuing on study intervention with azacitidine with or without glasdegib.

Study Overview

• Status: Completed
• Conditions: Acute Myeloid Leukemia; Chronic Myelomonocytic Leukemia; Myelodysplastic Syndrome
• Intervention / Treatment: Drug: Glasdegib; Drug: Azacitidine

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Salzburg, Austria, 5020
    • Landeskrankenhaus Salzburg, Universitatsklinik fur Innere Medizin III der PMU
  • Salzburg, Austria, 5020
    • Uniklinikum Salzburg, Landeskrankenhaus Salzburg
• Canada
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E 0V9
      • CancerCare Manitoba
    • Winnipeg, Manitoba, Canada, R3A 1R9
      • Health Sciences Centre
• Czechia
  • Ostrava - Poruba, Czechia, 708 52
    • Ustavni lekarna
  • Ostrava-Poruba, Czechia, 708 52
    • Klinika Hematoonkologie
• France
  • Nantes cedex, France, 44093
    • CHU de Nantes hotel Dieu
  • Nantes cedex 1, France, 44093
    • CHU de Nantes
• Hungary
  • Debrecen, Hungary, 4032
    • Debreceni Egyetem Klinikai Kozpont Belgyogyaszati Klinika, Hematologia Tanszek
  • Debrecen, Hungary, 4032
    • Debreceni Egyetem Klinikai Központ Belgyógyászati Klinika
• Italy
  • AN
    • Torette Di Ancona, AN, Italy, 60126
      • SOD Farmacia-Dipt dei servizi -AOU Ospedali Riuniti Umberto I, G.M. Lancisi, G. Salesi
  • Ancona
    • Torrette Di Ancona, Ancona, Italy, 60126
      • AOU Ospedali Riuniti Umberto I, G.M. Lancisi, G. Salesi, Clinica Di Ematologia
• Japan
  • Fukui
    • Yoshida-gun, Fukui, Japan, 910-1193
      • University of Fukui Hospital
  • Osaka
    • Osaka-City, Osaka, Japan, 545-8586
      • Osaka City University Hospital
• Mexico
  • MÉX
    • México, MÉX, Mexico, 14080
      • Instituto Nacional de Cancerologia
• Poland
  • Lodz, Poland, 93-513
    • WWCOiT im. M. Kopemlka w Lodzl
• Spain
  • Valencia, Spain, 46026
    • Hospital Universitari I Politecnic La Fe
• United Kingdom
  • Surry
    • Sutton, Surry, United Kingdom, SM2 5PT
      • The Royal Marsden NHS Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Any participant who continues to demonstrate clinical benefit (as determined by the Principal Investigator) from study treatment with azacitidine with or without glasdegib in this Study or from Study B1371012.
• Capable of giving signed informed consent as described in Appendix 1, which includes compliance with the requirements and restrictions listed in the ICD and in this protocol.

Exclusion Criteria:

• Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
• Female participants who are pregnant or breastfeeding (if continuing to receive study intervention);
• Participant has been withdrawn from Study B1371019 and Study B1371012 for any reason (including INT cohort participants required to end study treatment)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Participants from B1371019 and B1371012; Azacitidine will be administered 75 mg/m2/day for 7 days every 28 days on Days 1-7 (±3 days) per local label or per the IP Manual (or SPC). Azacitidine may be administered by SC injection or IV infusion. Alternate dosing schedules to administer the 7 doses to accommodate participant and treatment center availability are allowed. The starting dose regimen will be the same as the most recent regimen received on the B1371019 or B1371012 study. Glasdegib 50, 75 or 100 mg will be orally administered daily and continuously. The starting dose regimen will be the same as the most recent regimen received on the B1371012 or B1371019 study.

Drug: Glasdegib; 25 mg or 100 mg tablet; Other Names: PF-04449913; Drug: Azacitidine; 100 mg/vial powder for 25 mg/mL suspension for injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment Emergent Adverse Event (AE) and Treatment Related AE	AE was any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. An AE was considered treatment emergent if the event occurred during the on-treatment period (regardless of if it was seen prior to the start of treatment). An AE was considered treatment related as assigned by the investigator.	From initiation of study treatment to study completed from 17-May-2021 to 02-Dec-2022 (approximately 565 days)
Number of Participants With Treatment Emergent Serious Adverse Events (SAE) and Treatment Related SAEs	A SAE was defined as any untoward medical occurrence that, at any dose that resulted in death; was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent disability/incapacity, was a congenital anomaly/birth defect or other medical events as per investigator's judgement. A SAE was considered treatment emergent if the event occurred during the on-treatment period (regardless of if it was seen prior to the start of treatment). A SAE was considered treatment related as assigned by the investigator.	From initiation of study treatment to study completed from 17-May-2021 to 02-Dec-2022 (approximately 565 days)

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

• B1371019 (NCT03416179)

Study record dates

Study Major Dates

• Study Start (Actual): May 17, 2021
• Primary Completion (Actual): December 2, 2022
• Study Completion (Actual): December 2, 2022

Study Registration Dates

• First Submitted: April 8, 2021
• First Submitted That Met QC Criteria: April 8, 2021
• First Posted (Actual): April 13, 2021

Study Record Updates

• Last Update Posted (Estimated): December 18, 2023
• Last Update Submitted That Met QC Criteria: November 27, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Disease Attributes; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Myelodysplastic-Myeloproliferative Diseases; Chronic Disease; Myelodysplastic Syndromes; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia; Leukemia, Myelomonocytic, Chronic; Leukemia, Myelomonocytic, Juvenile; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Azacitidine
• Other Study ID Numbers: B1371019 Open Label Extension; 2017-002822-19 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No