Glasdegib for Chronic Graft-Versus-Host Disease

NCT04111497 | Terminated Phase 1 Results DMC FDA Drug

• 3 other identifiers: RG1005365NCI-2019-032448771
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 3

Brief Summary

This phase I/II trial studies whether glasdegib is helpful in treating sclerosis associated with chronic graft-versus-host disease. It will also investigate the safety of glasdegib in treating patients with chronic graft-versus-host disease.

Conditions

Chronic Graft Versus Host Disease; Fasciitis

Outcome Measures

Primary Outcomes (1)

• Number of Participants Who Experienced an Adverse Event

  Safety assessments will consist of monitoring and recording adverse events.

  From the start of treatment through 28 days after stopping study drug (Up to 25 months total)

Secondary Outcomes (8)

• Overall Response Rate (ORR) in Sclerotic Manifestations

  Up to 12 months after starting glasdegib

• ORR in All Chronic Graft Versus Host Disease (cGVHD) Manifestations

  Up to 12 months after the starting glasdegib

• Failure-free Survival

  At 12 months

• Symptom Burden Assessment - Absolute Change

  Cycle 4 (day 85) and End of Treatment (up through 24 months) [Due to lack of adequate data at cycles 7 (day 169) and 10 (day 253), they are not presented.]

• Quality of Life Assessment

  Cycle 4 (day 85) and End of Treatment (up through 24 months) [Due to lack of adequate data at cycles 7 (day 169) and 10 (day 253) they are not presented.]

Study Arms (1)

Treatment (glasdegib)

EXPERIMENTAL

Patients receive glasdegib PO QD on days 1-28. Cycles repeat every 28 days for up to 24 months in the absence of disease progression or unacceptable toxicity.

Drug: Glasdegib

Interventions

Glasdegib DRUG

Given PO

Also known as: 1095173-27-5, PF 04449913, PF-04449913, PF04449913

Treatment (glasdegib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosed with moderate or severe cGVHD according to the 2014 National Institute of Health (NIH) Consensus Criteria
• Diagnosed with cGVHD-related sclerosis or fasciitis
• Skin feature score of at least 2 OR
• Joints and fascia score of at least 1
• New, stable or progressive sclerosis/fasciitis despite treatment with at least one prior line of systemic therapy for cGVHD
• Female patients who:
• Are documented to be postmenopausal or are surgically sterile, OR
• If of childbearing potential, agree to use at least 1 highly effective method of contraception from the time of signing the informed consent form through 30 days after the last dose of study drug, OR agree to practice true abstinence or exclusively non-heterosexual activity when this is in line with the preferred and usual lifestyle of the subject
• Male patients who:
• Are surgically sterile (vasectomized) OR
• Agree to use at least 1 highly effective method of contraception during the entire study treatment period and through 30 days after the last dose of study drug, OR agree to practice true abstinence or exclusively non-heterosexual activity when this is in line with the preferred and usual lifestyle of the subject, AND
• Agree to use a condom to prevent potential transmission of investigational drug in seminal fluid
• Absolute neutrophil count (ANC) \> 1000/uL
• Platelet count \> 50 x 10\^9/mL
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \< 2 x upper limit of normal (ULN) unless attributed to cGVHD

You may not qualify if:

• Hospitalization for evaluation or management of an infection within the last 8 weeks
• Known organ dysfunction
• Uncontrolled cardiovascular disease, including arrhythmias, congestive heart failure
• Oxygen requirement
• Addition of any new systemic immunosuppressive treatment within the last 2 weeks
• \* Addition of new systemic immunosuppressive treatment along with glasdegib is also prohibited
• Corrected QT (QTc) interval \> 480 ms
• Female patients who are lactating or have a positive serum pregnancy test
• Major surgery within 14 days before enrollment
• \* Does not include placement of venous access device, bone marrow biopsy, GVHD diagnostic biopsy, or other routine procedures in chronic GVHD or post-transplantation care
• Use of any concomitant medications meds that are prohibited within the past 7 days
• Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol
• Known intolerance to glasdegib, sonidegib, or vismodegib
• Non-hematologic malignancy within the past 2 years with the exception of:
• Adequately treated basal cell carcinoma, squamous cell skin cancer, or thyroid cancer

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• Pfizer: collaborator

Study Sites (3)

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, 84112, United States

Location

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Bronchiolitis Obliterans Syndrome; Fasciitis

Interventions

glasdegib

Condition Hierarchy (Ancestors)

Organizing Pneumonia; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Graft vs Host Disease; Immune System Diseases; Musculoskeletal Diseases

Limitations and Caveats

Early termination led to a smaller than planned number of participants. Several participants met a study-defined endpoint (e.g. starting a new systemic GVHD therapy) or withdrew from the study after stopping study drug, limiting our ability to assess patient-reported outcomes over the long term.

Results Point of Contact

• Title: Dr. Stephanie Lee
• Organization: Fred Hutchinson Cancer Center

sjlee@fredhutch.org

206-667-6190

Study Officials

• Stephanie Lee

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: September 26, 2019
• First Posted: October 1, 2019
• Study Start: December 3, 2019
• Primary Completion: August 23, 2023
• Study Completion: August 23, 2023
• Last Updated: October 29, 2024
• Results First Posted: October 29, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)