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Chronic Graft Versus Host DiseasePhase 1/2NCT04111497

Glasdegib for Chronic Graft-Versus-Host Disease

A Phase 1/2 study testing Glasdegib in people with Chronic Graft Versus Host Disease and Fasciitis, run by Fred Hutchinson Cancer Center at 3 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Chronic Graft Versus Host Disease, Fasciitis
What is being tested?
Glasdegib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
15 participants
Where
3 sitesUnited States
Study dates
3 Dec 2019to 23 Aug 2023
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
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  • 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
  • Normal total bilirubin unless attributed to cGVHD
  • Creatinine < 2.0 mg/dl

Who cannot join

  • 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
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  • 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
  • Carcinoma in situ of the cervix or breast
  • Prostate cancer of Gleason grade 6 or less with stable prostate-specific antigen levels
  • Cancer considered cured by surgical resection or unlikely to impact survival during the duration of the study
  • Treatment with non-Food and Drug Administration (FDA) approved drug within 21 days of start of this trial
  • Evidence of recurrent or progressive underlying malignant disease
  • Karnofsky performance status < 70%
  • History of non-compliance
  • Life expectancy < 6 months
  • Grade 2 or 3 muscle cramping, or grade 1 muscle cramping that occurs at least weekly

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • Huntsman Cancer Institute/University of Utah

    Salt Lake City, Utah, 84112

  • Fred Hutch/University of Washington Cancer Consortium

    Seattle, Washington, 98109

Other trials in United States

About this study

Official title: A Single-Arm, Open-Label, Phase I/II Study of Glasdegib for Sclerotic Chronic Graft-Vs-Host Disease

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.

Read the detailed description

OUTLINE: This is a phase I/II study.

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

Being tested
Glasdegib
Medical subject headings
Bronchiolitis Obliterans Syndrome, Fasciitis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • GlasdegibDrug

    Also called 1095173-27-5, PF 04449913, PF-04449913, PF04449913

    Given PO

Study groups in NCT04111497
Study groupRoleWhat they receive
Treatment (glasdegib)ExperimentalPatients 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.
Receives: Drug: Glasdegib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants Who Experienced an Adverse Event

    Safety assessments will consist of monitoring and recording adverse events.

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

Secondary outcomes (8)

  1. Overall Response Rate (ORR) in Sclerotic Manifestations

    ORR will be calculated according to (1) the response definitions of the National Institute of Health (NIH) Consensus Conference for (a) skin or joint scores (0-3), where improvement by at least 1 point is a partial response (PR) and return to score 0 is a complete response (CR), or (b) the photographic range of motion scale (0-25) where improvement by at least 1 point is a PR and return to score 25 is a CR; and (2) change in the 0-10 sclerotic severity scale where at least a 2 point improvement is a PR or return to 0 (CR). Non-responders are those with mixed response (improvement in one regard and worsening in another), unchanged (stable), and progression.

    Measured: Up to 12 months after starting glasdegib

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

    ORR will be calculated according to the response definitions of the NIH Consensus Conference.

    Measured: Up to 12 months after the starting glasdegib

  3. Failure-free Survival

    Failure-free survival will be estimated using the Kaplan-Meier method (product limit estimator), with death, relapse, or start of another systemic immunosuppressive agent considered as events. Patients lost to follow-up or who withdraw consent will be censored.

    Measured: At 12 months

  4. Symptom Burden Assessment - Absolute Change

    Subjects will provide assessments of their symptom burden using a validated instrument recommended by the NIH Consensus on Chronic GVHD (Lee Chronic GVHD Symptom Scale). These will be collected before starting glasdegib on day 1 of cycle 1, and again on day (D)1, cycles 4, 7, 10 and end of treatment. Summary scores will be calculated based on published algorithms with absolute changes from baseline and clinically meaningful changes described for the population as a whole and based on CR+PR versus (vs.) stable disease (SD)+mixed response (MR)+progressive disease (PD), when adequate data are available for analysis.

    Lee Symptom Scale: minimum 0, maximum 100; higher score is worse outcome.

    Due to lack of adequate data at cycles 7 and 10, only Cycle 4 and End of Treatment are presented

    Measured: 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.]

  5. Quality of Life Assessment

    Subjects will provide assessments of their quality of life using the NIH-endorsed Patient Reported Outcomes Measurement Information System (PROMIS)-29. These will be collected before starting glasdegib on day 1 of cycle 1, and again on day (D)1, cycles 4, 7, 10 and end of treatment. Scores will be calculated based on published algorithms with absolute changes from baseline for the population as a whole and based on CR+PR versus stable disease (SD)+mixed response (MR)+progressive disease (PD), when adequate data are available for analysis.

    PROMIS-29 theoretical minimums and maximums are as follows:

    Physical Function: 22.5-57.0 Depression: 41.0-79.4 Anxiety: 40.3-81.6 Sleep Disturbance: 32.0-73.3 Fatigue: 33.7-75.8 Ability to Participate in Social Roles: 27.5-64.2 Pain Interference: 41.6-75.6 Higher score means a better outcome for Physical Function, Sleep Disturbance, and Social Roles.

    Higher score means a worse outcome for Anxiety, Depression, Fatigue, and Pain Interference.

    Measured: 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.]

  6. Biologic Impact of Hedgehog Pathway Inhibition

    Banking of blood and skin biopsy material for future biologic studies of hedgehog pathway inhibition.

    Measured: Up to 12 months

  7. Symptom Burden Assessment - Clinically Meaningful Change

    Subjects will provide assessments of their symptom burden using a validated instrument recommended by the NIH Consensus on Chronic GVHD (Lee Chronic GVHD Symptom Scale). These will be collected before starting glasdegib on day 1 of cycle 1, and again on day (D)1, cycles 4, 7, 10 and end of treatment. Summary scores will be calculated based on published algorithms with absolute changes from baseline and clinically meaningful changes described for the population as a whole and based on CR+PR versus (vs.) stable disease (SD)+mixed response (MR)+progressive disease (PD), when adequate data are available for analysis.

    Lee Symptom Scale: minimum 0, maximum 100; higher score is worse outcome.

    Due to lack of adequate data at cycles 7 and 10, only Cycle 4 and End of Treatment are presented

    Measured: 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.]

  8. Quality of Life Assessment - Clinically Meaningful Change

    Subjects will provide assessments of their quality of life using the NIH-endorsed Patient Reported Outcomes Measurement Information System (PROMIS)-29. These will be collected before starting glasdegib on day 1 of cycle 1, and again on day (D)1, cycles 4, 7, 10 and end of treatment. Scores for physical functioning will be calculated based on published algorithms with clinically meaningful changes described for the population as a whole and based on CR+PR versus (vs.) stable disease (SD)+mixed response (MR)+progressive disease (PD), when adequate data are available for analysis.

    PROMIS-29 minimums and maximums as follows:

    Physical Function: 22.5-57.0 Depression: 41.0-79.4 Anxiety: 40.3-81.6 Sleep Disturbance: 32.0-73.3 Fatigue: 33.7-75.8 Ability to Participate in Social Roles: 27.5-64.2 Pain Interference: 41.6-75.6 Higher score means a better outcome for Physical Function, Sleep, and Social Roles.

    Higher score means a worse outcome for Anxiety, Depression, Fatigue, and Pain.

    Measured: 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.]

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Oct 2019
  2. Study start3 Dec 2019
  3. Primary completion23 Aug 2023
  4. Study completion23 Aug 2023

Why it stopped: Study closed to accrual early due to side effects of study drug.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
15 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04111497
Sponsor's protocol ID
RG1005365
Other IDs
NCI-2019-03244, 8771
Status last verified
Oct 2024
First submitted
26 Sep 2019
Last updated
29 Oct 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Rodriguez-Arboli E, Lee CJ, Caballero-Velazquez T, Martinez C, Garcia-Calderon C, Jimenez-Leon MR, Bermudez-Rodriguez MA, Lopez-Corral L, Triguero A, Onstad L, Horwitz ME, Sarantopoulos S, Lee SJ, Perez-Simon JA. Targeting Hedgehog Signaling with Glasdegib in Patients with Refractory Sclerotic Chronic GVHD: A Report of Two Phase I/II Trials. Clin Cancer Res. 2023 Oct 13;29(20):4057-4067. doi: 10.1158/1078-0432.CCR-23-0666.

    PubMed 37698881

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Glasdegib in people with Chronic Graft Versus Host Disease and Fasciitis, run by Fred Hutchinson Cancer Center at 3 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 29 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 29 Oct 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants Who Experienced an Adverse Event (time frame: From the start of treatment through 28 days after stopping study drug (Up to 25 months total)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04111497, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Oct 2024.

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