Glasdegib for Chronic Graft-Versus-Host Disease
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT04111497|
Recruitment Status : Active, not recruiting
First Posted : October 1, 2019
Last Update Posted : June 15, 2022
|Condition or disease||Intervention/treatment||Phase|
|Chronic Graft Versus Host Disease Fasciitis||Drug: Glasdegib||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||15 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Single-Arm, Open-Label, Phase I/II Study of Glasdegib for Sclerotic Chronic Graft-Vs-Host Disease|
|Actual Study Start Date :||December 3, 2019|
|Estimated Primary Completion Date :||October 2023|
|Estimated Study Completion Date :||October 2023|
Experimental: Treatment (glasdegib)
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.
- Incidence of adverse events [ Time Frame: Up to 12 months ]Safety assessments will consist of monitoring and recording adverse events.
- Overall response rate (ORR) in sclerotic manifestations [ Time Frame: Up to 12 months after the starting glasdegib ]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 PR and return to score 0 is a complete (CR), or (b) the photographic range of motion scale (0-25) where improvement by at least 1 point is a partial response (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).
- ORR in all chronic graft versus host disease (cGVHD) manifestations [ Time Frame: Up to 12 months after the starting glasdegib ]ORR will be calculated according to the response definitions of the NIH Consensus Conference. ORR both including and excluding skin sclerotic features will be reported.
- Failure-free survival [ Time Frame: At 12 months ]Will be estimated with events considered death, relapse, or start of another systemic immunosuppressive agent. Patients lost to follow-up or who withdraw consent will be censored.
- Symptom Burden Assessment [ Time Frame: At 12 months ]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.
- Quality of Life Assessment [ Time Frame: At 12 months ]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 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.
- Biologic impact of hedgehog pathway inhibition [ Time Frame: Up to 12 months ]Aim to discern the biologic impact of Hedgehog pathway inhibition in the treatment of cGVHD and may include the following skin assays as well as others: expression of Shh, Gli1, Gli2, ptch-2, collagen, TGFb, and Smo. Immunohistochemistry may be performed for Patched, Shh, Snail, GSK3-beta, beta-catenin, or Ihh as well as other markers.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04111497
|United States, North Carolina|
|Duke University Medical Center|
|Durham, North Carolina, United States, 27710|
|United States, Utah|
|Huntsman Cancer Institute/University of Utah|
|Salt Lake City, Utah, United States, 84112|
|United States, Washington|
|Fred Hutch/University of Washington Cancer Consortium|
|Seattle, Washington, United States, 98109|
|Principal Investigator:||Stephanie Lee||Fred Hutch/University of Washington Cancer Consortium|