Sclerodermoid Chronic Graft-Versus-Host Disease (Disorder)Phase 1/2NCT03415867
Glasdegib in Refractory Patients With Sclerotic Chronic Graft-Versus-Host Disease
A Phase 1/2 study testing Glasdegib in people with Sclerodermoid Chronic Graft-Versus-Host Disease (Disorder), run by Grupo Espanol de trasplantes hematopoyeticos y terapia celular at 6 sites in Spain.
Trial summary
This is a phase 1b/2a, open label, multi-centre, safety and efficacy study of glasdegib in patients with sclerotic cGVHD refractory to second-line treatment. The design for the current study is a standard 3+3 dose-finding scheme. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Sclerodermoid Chronic Graft-Versus-Host Disease (Disorder)
- What is being tested?
- Glasdegib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 6 sitesSpain
- Study dates
- 9 Jan 2018to 9 Jun 2022
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
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
- Adult (≥ 18 years old) recipients of an allogeneic hematopoietic stem cell transplantation with active sclerotic cGVHD without response, in partial response or in relapse after 2 previous lines of treatment including corticosteroids and one of the following second line treatments:
- Extracorporeal photopheresis (preferably).
- A calcineurin inhibitor.
- A mammalian target of rapamycin (mTOR) inhibitor.
- Pentostatin.
- Rituximab.
Show all 18Show fewer
- Imatinib.
- Ruxolitinib.
- Eastern Cooperative Oncology Group Performance Status 0 to 2.
- Adequate organ function as defined by the following:
- Serum aspartate aminotransferase (AST) and serum alanine aminotransferase (ALT) ≤ 3 x upper limit of normal (ULN).
- Total serum bilirubin ≤ 2 x ULN (except patients with documented Gilbert's syndrome).
- Serum creatinine ≤ 1.5 x ULN or estimated creatinine clearance ≥ 60 mL/min as calculated using the method standard for the institution.
- Hematologic malignancy in complete remission.
- Resolved acute effects of any prior therapy to baseline severity or Grade ≤ 1 CTCAE except for adverse events not constituting a safety risk by investigator judgement.
- Serum/urine pregnancy test (for females of childbearing potential) that is negative at screening and immediately prior to initiation of treatment (first dose). Male and female patients of childbearing potential must agree to use highly effective methods of contraception throughout the study and for at least 180 days after the last dose of assigned treatment. A patient is of childbearing potential if, in the opinion of the investigator, he/she is biologically capable of having children and is sexually active.
- Evidence of a personally signed and dated informed consent document indicating that the patient (or a legal representative) has been informed of all pertinent aspects of the study.
- Willingness and ability to comply with the study scheduled visits, treatment plans, laboratory tests and other procedures.
Who cannot join
- Patients presenting with any of the following will not be included in the study:
- Patients with active malignancy with the exception of basal cell carcinoma, nonmelanoma skin cancer or cervical carcinoma-in-situ. Other prior or concurrent malignancies will be considered on a case-by-case basis.
- Any one of the following, currently or in the previous 6 months: myocardial infarction, congenital long QT syndrome, torsade de pointes or clinically significant ventricular arrhythmias.
- QTc interval >470 milliseconds using the Fridericia (QTcF).
- Patients with an active, life threatening or clinically significant uncontrolled systemic infection.
- Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness or active Hepatitis B or C infection.
Show all 19Show fewer
- Known malabsorption syndrome or other condition that may impair absorption of study medication (e.g., gastrectomy or lap band).
- Major surgery or radiation within 4 weeks of starting study treatment.
- Prior treatment with:
- A hedgehog inhibitor at any time.
- An investigational agent for the treatment of cGVHD (a three-month wash-out period will be required).
- Concurrent treatment with any investigational agent.
- Concurrent administration of herbal preparations.
- Current use at time of study entry or anticipated need for drugs that are known strong CYP3A4/5 inducers.
- Current drug or alcohol abuse.
- Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
- Patients who are investigational site staff members or relatives of those site staff members directly involved in the conduct of the trial.
- Pregnant females; breastfeeding females; males and females of childbearing potential not using two methods of highly effective contraception or not agreeing to continue two methods of highly effective contraception for at least 180 days after last dose of investigational product.
- Recent or active suicidal ideation or behaviour.
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
Spain6 sites
Hospital Clinic de Barcelona
Barcelona
Hospital General Universitario Morales Meseguer
Murcia
Hospital Universitario Son Espases
Palma de Mallorca
Hospital Universitario de Salamanca
Salamanca
Hospital Universitario Marqués de Valdecilla
Santander
Hospital Universitario Virgen del Rocío
Seville
About this study
Official title: A Phase 1b/ 2a Pilot Trial of the Oral Hedgehog Signalling Inhibitor Glasdegib in Patients With Sclerotic Chronic Graft-Versus-Host Disease Refractory to Second-Line Treatment
This is a phase 1b/2a, open label, multi-centre, safety and efficacy study of glasdegib in patients with sclerotic cGVHD refractory to second-line treatment. The design for the current study is a standard 3+3 dose-finding scheme. A dose escalation/de-escalation design will be applied in successive patient cohorts until identification of MTD. Glasdegib will be self-administered orally once daily in the morning as monotherapy in continuous 28-day treatment cycles for a maximum of 24 cycles. Those patients enrolled in the trial that obtain objective clinical benefit under treatment with glasdegib (defined as the achievement of at least a partial response at one or more target organs), will be allowed to proceed to a slow dose withdrawal phase over a period of 6 months after the end of Cycle 24.
Read the detailed description
Three patients will be initially treated at the corresponding dose level of glasdegib at each dose escalation stage. Dose escalation will be started in a first cohort of 3 patients at a starting dose of 50 mg (Dose Level 1) and will then proceed as follows:
- If no dose-limiting toxicity is observed among the first 3 patients in a cohort, then 3 additional patients will be treated at the next higher dose level.
- If a dose-limiting toxicity is observed in 1 of the initial 3 treated patients, 3 additional patients, resulting in a total of 6 patients, will be enrolled and treated at the same dose level.
- If no further dose-limiting toxicity is observed (1/6 patients), dose escalation will continue to the next dose level in a new cohort of 3 patients.
- If ≥ 2/3 or 2/6 patients experience a dose-limiting toxicity, then MTD has been exceeded and the next lower dose of glasdegib will be expanded until a total number of 6 patients treated at that dose level is reached. If 0 or 1 patient out of 6 experiences a dose-limiting toxicity, this dose level will be declared MTD. If ≥ 2/6 patients experience a dose-limiting toxicity, the next lower dose level will be expanded.
- Prior safety data evaluation and approval by an independent data monitoring committee will be required before escalation at each dose level.
In case that MTD is exceeded within the first cohort, then a -1 Dose Level (25 mg OD) will be tested. If MTD is exceeded at 25 mg OD, the trial will be stopped and no additional testing of glasdegib at lower doses will be allowed.
Dose escalation will continue following the above-specified rules until MTD is declared. Once MTD is defined, dose expansion at MTD in cohorts of 3 patients will proceed until the pre-established sample size (20 patients) is reached. In the event that the highest pre-defined dose (200 mg OD) is tested in two successive cohorts of 3 patients and MTD is not attained, dose expansion at 200 mg OD will precede until a sample size of 20 patients is reached. The administered dose level may be subject to further adjustment (dose reduction only) in the dose expansion phase based on emerging safety, pharmacokinetic or pharmacodynamic data.
Additional dose levels may be explored, if appropriate, based on emerging safety, pharmacokinetic, or pharmacodynamic data, prior safety data evaluation and approval by an external monitoring committee.
Patients who are not evaluable for dose-limiting toxicity (e.g., those not receiving at least 80% of the planned dose of glasdegib in the dose-limiting toxicity monitoring period (first 2 cycles) for reasons other than study treatment-related toxicities) must be replaced.
If the pre-specified sample size is completed before MTD is defined or before the highest pre-defined dose (200 mg OD) is tested in at least 6 patients, additional patients may be recruited into the study (for a total sample size of up to 24 patients) until MTD is defined or two cohorts of 3 patients complete treatment at 200 mg OD.
Glasdegib may be dose reduced or discontinued during any cycle based on the patient's individual tolerability. During the dose-escalation phase, once a patient has a dose reduction for a study drug-related toxicity; the dose will not be re-escalated. Dose re-escalation up to the MTD will be allowed at the investigator's discretion during the dose expansion phase.
- Being tested
- Glasdegib
- Keywords
- Graft-versus-host disease, Bone marrow transplantation, Hedgehog inhibitor
- Medical subject headings
- Graft vs Host Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GlasdegibDrug
Also called PF-04449913
A dose escalation/de-escalation design will be applied in successive patient cohorts until identification of MTD (dose range: 25-200 mg OD).
| Study group | Role | What they receive |
|---|---|---|
| Dose escalation sequential cohorts | Experimental | Glasdegib will be self-administered orally once daily in the morning as monotherapy in continuous 28-day treatment cycles for a maximum of 24 cycles. Those patients enrolled in the trial that obtain objective clinical benefit under treatment with glasdegib (defined as the achievement of at least a partial response at one or more target organs), will be allowed to proceed to a slow dose withdrawal phase over a period of 6 months after the end of Cycle 24. The dose reduction scheme is fully detailed in the protocol. Receives: Drug: Glasdegib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose.
To determine the maximum tolerated dose (MTD) or maximum administered dose (MAD) and/or the recommended Phase 2 dose (RP2D) of glasdegib in subjects with sclerotic cGVHD.
Measured: Up to 48 weeks.
Secondary outcomes (12)
Adverse events.
Type, incidence, severity (graded by the National Cancer Institute [NCI] Common.
Terminology Criteria for Adverse Events [CTCAE], Version 4.0), timing, intensity, and relatedness of adverse events.
Measured: Adverse events will be assessed from the date the informed consent document is signed until 28 days after the last administered dose of glasdegib.
Overall response rate (ORR).
ORR as assessed by the NIH cGVHD Response Criteria.
Measured: Response to treatment will be evaluated on Day 1 of Cycles 1, 2, 4, 7, 10, 13, 16, 19, 22, 25, 28 (each cycle is 28 days) and end treatment.
Immunosuppression requirements.
Dose reduction and/or withdrawal of concomitantly administered immunosuppressive drugs.
Measured: Modifications to the immunosuppressive regimen will be assessed from date of study entry to study withdrawal or end of treatment (up to 48 weeks).
Duration of clinical response.
Duration of clinical response as assessed by the NIH cGVHD Response Criteria.
Measured: Response to treatment will be evaluated on Day 1 of Cycles 1, 2, 4, 7, 10, 13, 16, 19, 22, 25, 28 (each cycle is 28 days) and day 28 of Cycle 24,
Survival outcomes: overall survival.
Overall survival (OS).
Measured: Survival status of participants will be followed from inclusion to end of trial (once every recruited patient has completed 12 cycles of treatment or withdrawn from the study).
Survival outcomes: progression-free survival.
Progression-free survival (PFS).
Measured: Progression-free survival status of participants will be followed from inclusion to end of trial (once every recruited patient has completed 12 cycles of treatment or withdrawn from the study).
Pharmacokinetics: elimination half-life.
Elimination half-life of glasdegib.
Measured: Day 1 of Cycles 1, 2 and 4 (each cycle is 28 days).
Pharmacokinetics: AUC.
Area under the plasma concentration versus time curve (AUC) for each dose group.
Measured: Day 1 of Cycles 1, 2 and 4 (each cycle is 28 days).
Pharmacokinetics: Cmax.
Maximum plasma concentration (Cmax) for each dose group.
Measured: Day 1 of Cycles 1, 2 and 4 (each cycle is 28 days).
Pharmacodynamics: Gli1 expression.
To explore the relationship of glasdegib plasma levels and Gli1 expression in peripheral blood mononuclear cells.
Measured: Day 1 of Cycle 1 and Cycle 2, 4 , 13 and 25 (or End of Treatment if the patient does not subsequently proceed to the dose reduction phase) .
Pharmacodynamics: Gli2 expression
To explore the relationship of glasdegib plasma levels and Gli2 expression in peripheral blood mononuclear cells.
Measured: Day 1 of Cycle 1 and Cycle 2, 4 , 13 and 25 (or End of Treatment if the patient does not subsequently proceed to the dose reduction phase) .
Pharmacodynamics: Shh expression.
To explore the relationship of glasdegib plasma levels and Shh expression in peripheral blood mononuclear cells.
Measured: Day 1 of Cycle 1 and Cycle 2, 4 , 13 and 25 (or End of Treatment if the patient does not subsequently proceed to the dose reduction phase) .
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jan 2018
- Study start9 Jan 2018
- Primary completion9 Jan 2022
- Study completion9 Jun 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Sclerodermoid Chronic Graft-Versus-Host Disease (Disorder)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Sequential
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- Grupo Espanol de trasplantes hematopoyeticos y terapia celular
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- José Antonio Pérez-Simón, M.D. Ph.D., Study chair, Department of Hematology, Hospital Universitario Virgen del Rocío. Spain
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03415867
- Sponsor's protocol ID
- GLAS
- Other IDs
- 2017-000862-31, 2017
- Status last verified
- Mar 2022
- First submitted
- 5 Dec 2017
- Last updated
- 17 Mar 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Anonymized data for primary and secondary variables is planned to be shared with all participants within 6 months of data completion
Publications
Inamoto Y, Storer BE, Petersdorf EW, Nelson JL, Lee SJ, Carpenter PA, Sandmaier BM, Hansen JA, Martin PJ, Flowers ME. Incidence, risk factors, and outcomes of sclerosis in patients with chronic graft-versus-host disease. Blood. 2013 Jun 20;121(25):5098-103. doi: 10.1182/blood-2012-10-464198. Epub 2013 Apr 1.
PubMed 23547053Dignan FL, Amrolia P, Clark A, Cornish J, Jackson G, Mahendra P, Scarisbrick JJ, Taylor PC, Shaw BE, Potter MN; Haemato-oncology Task Force of British Committee for Standards in Haematology; British Society for Blood and Marrow Transplantation. Diagnosis and management of chronic graft-versus-host disease. Br J Haematol. 2012 Jul;158(1):46-61. doi: 10.1111/j.1365-2141.2012.09128.x. Epub 2012 Apr 26.
PubMed 22533811Zerr P, Palumbo-Zerr K, Distler A, Tomcik M, Vollath S, Munoz LE, Beyer C, Dees C, Egberts F, Tinazzi I, Del Galdo F, Distler O, Schett G, Spriewald BM, Distler JH. Inhibition of hedgehog signaling for the treatment of murine sclerodermatous chronic graft-versus-host disease. Blood. 2012 Oct 4;120(14):2909-17. doi: 10.1182/blood-2012-01-403428. Epub 2012 Aug 22.
PubMed 22915638Rodriguez-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
Study at a glance
From the registry record, last updated by the sponsor on 17 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b/ 2a Pilot Trial of the Oral Hedgehog Signalling Inhibitor Glasdegib in Patients With Sclerotic Chronic Graft-Versus-Host Disease Refractory to Second-Line Treatment
- ClinicalTrials.gov ID
- NCT03415867
- Acronym / sponsor ID
- GLAS
- Keywords
- Graft-versus-host disease, Bone marrow transplantation, Hedgehog inhibitor
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 21 participants (actual)
- Lead sponsor
- Grupo Espanol de trasplantes hematopoyeticos y terapia celularUniversity, hospital or other
- Study start
- 9 Jan 2018 (actual)
- Primary completion
- 9 Jan 2022 (actual)
- Study completion
- 9 Jun 2022 (estimated)
- First posted
- 30 Jan 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a phase 1b/2a, open label, multi-centre, safety and efficacy study of glasdegib in patients with sclerotic cGVHD refractory to second-line treatment. The design for the current study is a standard 3+3 dose-finding scheme. A dose escalation/de-escalation design will be applied in successive patient cohorts until identification of MTD. Glasdegib will be self-administered orally once daily in the morning as monotherapy in continuous 28-day treatment cycles for a maximum of 24 cycles. Those patients enrolled in the trial that obtain objective clinical benefit under treatment with glasdegib (defined as the achievement of at least a partial response at one or more target organs), will be allowed to proceed to a slow dose withdrawal phase over a period of 6 months after the end of Cycle 24.
Detailed description
Three patients will be initially treated at the corresponding dose level of glasdegib at each dose escalation stage. Dose escalation will be started in a first cohort of 3 patients at a starting dose of 50 mg (Dose Level 1) and will then proceed as follows:
- If no dose-limiting toxicity is observed among the first 3 patients in a cohort, then 3 additional patients will be treated at the next higher dose level.
- If a dose-limiting toxicity is observed in 1 of the initial 3 treated patients, 3 additional patients, resulting in a total of 6 patients, will be enrolled and treated at the same dose level.
- If no further dose-limiting toxicity is observed (1/6 patients), dose escalation will continue to the next dose level in a new cohort of 3 patients.
- If ≥ 2/3 or 2/6 patients experience a dose-limiting toxicity, then MTD has been exceeded and the next lower dose of glasdegib will be expanded until a total number of 6 patients treated at that dose level is reached. If 0 or 1 patient out of 6 experiences a dose-limiting toxicity, this dose level will be declared MTD. If ≥ 2/6 patients experience a dose-limiting toxicity, the next lower dose level will be expanded.
- Prior safety data evaluation and approval by an independent data monitoring committee will be required before escalation at each dose level.
In case that MTD is exceeded within the first cohort, then a -1 Dose Level (25 mg OD) will be tested. If MTD is exceeded at 25 mg OD, the trial will be stopped and no additional testing of glasdegib at lower doses will be allowed.
Dose escalation will continue following the above-specified rules until MTD is declared. Once MTD is defined, dose expansion at MTD in cohorts of 3 patients will proceed until the pre-established sample size (20 patients) is reached. In the event that the highest pre-defined dose (200 mg OD) is tested in two successive cohorts of 3 patients and MTD is not attained, dose expansion at 200 mg OD will precede until a sample size of 20 patients is reached. The administered dose level may be subject to further adjustment (dose reduction only) in the dose expansion phase based on emerging safety, pharmacokinetic or pharmacodynamic data.
Additional dose levels may be explored, if appropriate, based on emerging safety, pharmacokinetic, or pharmacodynamic data, prior safety data evaluation and approval by an external monitoring committee.
Patients who are not evaluable for dose-limiting toxicity (e.g., those not receiving at least 80% of the planned dose of glasdegib in the dose-limiting toxicity monitoring period (first 2 cycles) for reasons other than study treatment-related toxicities) must be replaced.
If the pre-specified sample size is completed before MTD is defined or before the highest pre-defined dose (200 mg OD) is tested in at least 6 patients, additional patients may be recruited into the study (for a total sample size of up to 24 patients) until MTD is defined or two cohorts of 3 patients complete treatment at 200 mg OD.
Glasdegib may be dose reduced or discontinued during any cycle based on the patient's individual tolerability. During the dose-escalation phase, once a patient has a dose reduction for a study drug-related toxicity; the dose will not be re-escalated. Dose re-escalation up to the MTD will be allowed at the investigator's discretion during the dose expansion phase.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Dose escalation sequential cohorts | Experimental | Drug: GlasdegibGlasdegib will be self-administered orally once daily in the morning as monotherapy in continuous 28-day treatment cycles for a maximum of 24 cycles. Those patients enrolled in the trial that obtain objective clinical benefit under treatment with glasdegib (defined as the achievement of at least a partial response at one or more target organs), will be allowed to proceed to a slow dose withdrawal phase over a period of 6 months after the end of Cycle 24. The dose reduction scheme is fully detailed in the protocol. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Adult (≥ 18 years old) recipients of an allogeneic hematopoietic stem cell transplantation with active sclerotic cGVHD without response, in partial response or in relapse after 2 previous lines of treatment including corticosteroids and one of the following second line treatments:
- Eastern Cooperative Oncology Group Performance Status 0 to 2.
- Adequate organ function as defined by the following:
- Hematologic malignancy in complete remission.
- Resolved acute effects of any prior therapy to baseline severity or Grade ≤ 1 CTCAE except for adverse events not constituting a safety risk by investigator judgement.
Key exclusion criteria (19 listed)
- Patients with active malignancy with the exception of basal cell carcinoma, nonmelanoma skin cancer or cervical carcinoma-in-situ. Other prior or concurrent malignancies will be considered on a case-by-case basis.
- Any one of the following, currently or in the previous 6 months: myocardial infarction, congenital long QT syndrome, torsade de pointes or clinically significant ventricular arrhythmias.
- QTc interval >470 milliseconds using the Fridericia (QTcF).
- Patients with an active, life threatening or clinically significant uncontrolled systemic infection.
- Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness or active Hepatitis B or C infection.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GlasdegibAlso: PF-04449913A dose escalation/de-escalation design will be applied in successive patient cohorts until identification of MTD (dose range: 25-200 mg OD). | Drug | Dose escalation sequential cohorts |
Primary outcome
Maximum tolerated dose.
Time frame: Up to 48 weeks.
To determine the maximum tolerated dose (MTD) or maximum administered dose (MAD) and/or the recommended Phase 2 dose (RP2D) of glasdegib in subjects with sclerotic cGVHD.
12 secondary outcomes
Adverse events.
Time frame: Adverse events will be assessed from the date the informed consent document is signed until 28 days after the last administered dose of glasdegib.
Overall response rate (ORR).
Time frame: Response to treatment will be evaluated on Day 1 of Cycles 1, 2, 4, 7, 10, 13, 16, 19, 22, 25, 28 (each cycle is 28 days) and end treatment.
Immunosuppression requirements.
Time frame: Modifications to the immunosuppressive regimen will be assessed from date of study entry to study withdrawal or end of treatment (up to 48 weeks).
Duration of clinical response.
Time frame: Response to treatment will be evaluated on Day 1 of Cycles 1, 2, 4, 7, 10, 13, 16, 19, 22, 25, 28 (each cycle is 28 days) and day 28 of Cycle 24,
Survival outcomes: overall survival.
Time frame: Survival status of participants will be followed from inclusion to end of trial (once every recruited patient has completed 12 cycles of treatment or withdrawn from the study).
Survival outcomes: progression-free survival.
Time frame: Progression-free survival status of participants will be followed from inclusion to end of trial (once every recruited patient has completed 12 cycles of treatment or withdrawn from the study).
Pharmacokinetics: elimination half-life.
Time frame: Day 1 of Cycles 1, 2 and 4 (each cycle is 28 days).
Pharmacokinetics: AUC.
Time frame: Day 1 of Cycles 1, 2 and 4 (each cycle is 28 days).
Pharmacokinetics: Cmax.
Time frame: Day 1 of Cycles 1, 2 and 4 (each cycle is 28 days).
Pharmacodynamics: Gli1 expression.
Time frame: Day 1 of Cycle 1 and Cycle 2, 4 , 13 and 25 (or End of Treatment if the patient does not subsequently proceed to the dose reduction phase) .
Pharmacodynamics: Gli2 expression
Time frame: Day 1 of Cycle 1 and Cycle 2, 4 , 13 and 25 (or End of Treatment if the patient does not subsequently proceed to the dose reduction phase) .
Pharmacodynamics: Shh expression.
Time frame: Day 1 of Cycle 1 and Cycle 2, 4 , 13 and 25 (or End of Treatment if the patient does not subsequently proceed to the dose reduction phase) .
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Mar 2022.
- Background: PubMed 23547053Inamoto Y, Storer BE, Petersdorf EW, Nelson JL, Lee SJ, Carpenter PA, Sandmaier BM, Hansen JA, Martin PJ, Flowers ME. Incidence, risk factors, and outcomes of sclerosis in patients with chronic graft-versus-host disease. Blood. 2013 Jun 20;121(25):5098-103. doi: 10.1182/blood-2012-10-464198. Epub 2013 Apr 1.
- Background: PubMed 22533811Dignan FL, Amrolia P, Clark A, Cornish J, Jackson G, Mahendra P, Scarisbrick JJ, Taylor PC, Shaw BE, Potter MN; Haemato-oncology Task Force of British Committee for Standards in Haematology; British Society for Blood and Marrow Transplantation. Diagnosis and management of chronic graft-versus-host disease. Br J Haematol. 2012 Jul;158(1):46-61. doi: 10.1111/j.1365-2141.2012.09128.x. Epub 2012 Apr 26.
- Background: PubMed 22915638Zerr P, Palumbo-Zerr K, Distler A, Tomcik M, Vollath S, Munoz LE, Beyer C, Dees C, Egberts F, Tinazzi I, Del Galdo F, Distler O, Schett G, Spriewald BM, Distler JH. Inhibition of hedgehog signaling for the treatment of murine sclerodermatous chronic graft-versus-host disease. Blood. 2012 Oct 4;120(14):2909-17. doi: 10.1182/blood-2012-01-403428. Epub 2012 Aug 22.
- Derived from this study: PubMed 37698881Rodriguez-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.
- Individual participant dataSharing planned: Yes. Anonymized data for primary and secondary variables is planned to be shared with all participants within 6 months of data completion
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
José Antonio Pérez-Simón, M.D. Ph.D. study chair
Department of Hematology, Hospital Universitario Virgen del Rocío. Spain
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Glasdegib in people with Sclerodermoid Chronic Graft-Versus-Host Disease (Disorder), run by Grupo Espanol de trasplantes hematopoyeticos y terapia celular at 6 sites in Spain.
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 18 inclusion and 19 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: status not confirmed, as of the sponsor's last update on 17 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Spain. 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?
Results are not available in the source record.
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?
Maximum tolerated dose. (time frame: Up to 48 weeks.). 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 NCT03415867, which also lists 4 linked publications.
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 17 Mar 2022.