Chronic Graft-versus-host DiseasePhase 2NCT01898377
Imatinib Mesylate and Mycophenolate Mofetil for Steroid-Refractory Sclerotic/Fibrotic cGVHD in Children
A Phase 2 study testing Imatinib mesylate, Mycophenolate mofetil in people with Chronic Graft-versus-host Disease, run by Seoul National University Hospital at 1 site in South Korea.
Trial summary
In this study we will combine mycophenolate mofetil and imatinib mesylate to treat steroid-refractory sclerotic/fibrotic type chronic graft-versus-host disease (GVHD) to see the response rate and to find the safety of combination. Read more about this study
- Who is it for?
- Ages Up to 21 years
- Conditions the study is for
- Chronic Graft-versus-host Disease
- What is being tested?
- Imatinib mesylate, Mycophenolate mofetil
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteSouth Korea
- Study dates
- Aug 2013to 14 Feb 2018
- Phase
- Phase 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 Up to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Patients must have a diagnosis of chronic GVHD with fibrotic/scleroderma-like features. This diagnosis can be made clinically or by histopathology.
- Patients must have active disease with at least one of the following manifestations: skin sclerosis, symptomatic bronchiolitis obliterans, extensive lung fibrosis, pathologically demonstrated visceral fibrotic involvement of the gut.
- Patients with corticosteroid refractory or dependant cGVHD are eligible. Steroid-refractory chronic GVHD is defined as chronic GVHD of sustained severity during the last full month during which the patients received the equivalent of prednisone 0.5 mg/kg or more per day or 1 mg/kg or more every other day.
- Age under 21 years old
Who cannot join
- Patients who have had chemotherapy, radiotherapy within 4 weeks prior to entering the study.
- Patients who have not recovered from adverse events.
- Prior treatment with imatinib mesylate or other tyrosine kinase inhibitor after the date of transplant.
- Patients on pregnancy or lactating
Trial locations and contacts
1 site in 1 country.
South Korea1 site
Seoul National University Children's Hospital
Seoul, Chongno-gu
About this study
Official title: Open-label, Multicenter Phase II Study of Combination Therapy of Imatinib Mesylate and Mycophenolate Mofetil in Children With Steroid-Refractory Sclerotic/Fibrotic Type Chronic Graft-versus-host Disease
In this study we will combine mycophenolate mofetil and imatinib mesylate to treat steroid-refractory sclerotic/fibrotic type chronic graft-versus-host disease (GVHD) to see the response rate and to find the safety of combination.
Read the detailed description
Sclerotic/fibrotic type chronic GVHD is one of the most severe forms of the disease and is frequently refractory to standard treatment approaches. Imatinib mesylate, a tyrosine kinase inhibitor, has been shown to be effective in patients with sclerotic/fibrotic type chronic GVHD by strongly inhibiting both PDGF (Platelet-derived growth factor) and TGF-β (transforming growth factor-β) intracellular signaling, which is responsible for the expression of extracellular matrix genes.
Mycophenolate mofetil (MMF) is one of effective agent for the treatment of chronic graft-versus-host disease. MMF is rapidly absorbed after oral administration and hydrolyzed to the active metabolite, MPA (mycophenolic acid). MPA selectively inhibits inosine monophosphate dehydrogenase, blocking the pathway of purine synthesis in T and B lymphocytes. In this study we will combine MMF and imatinib mesylate to treat steroid-refractory sclerotic/fibrotic type chronic GVHD to see the response rate and to find the safety of combination.
- Conditions
- Chronic Graft-versus-host Disease
- Being tested
- Imatinib mesylate, Mycophenolate mofetil
- Keywords
- Children, Chronic graft-versus-host disease
- Medical subject headings
- Bronchiolitis Obliterans Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Imatinib mesylate, Mycophenolate mofetilDrug
Also called Glivec, Cellcept
| Study group | Role | What they receive |
|---|---|---|
| Imatinib mesylate, Mycophenolate mofetil | Experimental | MMF 15-20mg/kg (Max 1 g) bid + Imatinib mesylate qd
* Dose of imatinib : starting dose 260 mg/m2/d (Max. 400 mg)
* Imatinib dose adjustment : Dose is adjusted according to the guidelines if there is serious adverse event, toxicity, or intolerance. Receives: Drug: Imatinib mesylate, Mycophenolate mofetil |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall (complete and partial) response rate
Response evaluation will be performed every 3 months during the treatment by comprehensive response criteria based on NIH criteria. The complete and partial response categories apply only to organs that have measurable and reversible GVHD-related abnormalities at baseline.
- Complete response (CR): Resolution of all signs and symptoms of chronic GVHD
- Partial response (PR) : Improvement (at least 1 clinical score reduction, see Appendix 2) in 1 or more organs of involvement and no evidence of worsening in any organ
- Objective response (OR): Either CR or PR
Measured: 1 year
Secondary outcomes (4)
Evaluate the safety profile of MMF plus imatinib mesylate
All adverse events will be recorded on the "Adverse Events CRF" with the following information
- Severity grade (NCI CTCAE ver. 4.0)
- Relationship to the study drug
- Duration (start and end dates or if continuing at final exam)
- Whether it constitutes a serious adverse event (SAE)
Measured: 1 year
Evaluate the quality of life (QOL)
The assessment of QOL will be performed at baseline and every 3 months till 1 year with Lee cGVHD Symptom Scale.
Measured: 1 year
Discontinuation of steroid
- Based on the response during study period, investigators could modify the dosage of concomitant immunosuppressive agents in the same manner as corticosteroid.
- The rate of discontinuation among patients and the dose change from baseline of each patient.
Measured: 1 year
Overall survival rate
For survival outcome, Kaplan-Meier method will be used for estimation.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jul 2013 (estimated)
- Study startAug 2013
- Primary completion14 Feb 2018
- Study completion14 Feb 2018
Why it stopped: New treatment option introduced for patients with the study indication
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Graft-versus-host DiseaseStudies of the same condition, open and under way.
- More trials run by Seoul National University HospitalThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Seoul National University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Hyoung Jin Kang, MD, Ph.D, Principal investigator, Seoul National University Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01898377
- Sponsor's protocol ID
- SNUCH-1301
- Status last verified
- Oct 2020
- First submitted
- 5 Jun 2013
- Last updated
- 23 Oct 2020
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Open-label, Multicenter Phase II Study of Combination Therapy of Imatinib Mesylate and Mycophenolate Mofetil in Children With Steroid-Refractory Sclerotic/Fibrotic Type Chronic Graft-versus-host Disease
- ClinicalTrials.gov ID
- NCT01898377
- Acronym / sponsor ID
- SNUCH-1301
- Conditions
- Chronic Graft-versus-host Disease
- Keywords
- Children, Chronic graft-versus-host disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: New treatment option introduced for patients with the study indication
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Seoul National University HospitalUniversity, hospital or other
- Study start
- Aug 2013
- Primary completion
- 14 Feb 2018 (actual)
- Study completion
- 14 Feb 2018 (actual)
- First posted
- 12 Jul 2013 (estimated)
- 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.
In this study we will combine mycophenolate mofetil and imatinib mesylate to treat steroid-refractory sclerotic/fibrotic type chronic graft-versus-host disease (GVHD) to see the response rate and to find the safety of combination.
Detailed description
Sclerotic/fibrotic type chronic GVHD is one of the most severe forms of the disease and is frequently refractory to standard treatment approaches. Imatinib mesylate, a tyrosine kinase inhibitor, has been shown to be effective in patients with sclerotic/fibrotic type chronic GVHD by strongly inhibiting both PDGF (Platelet-derived growth factor) and TGF-β (transforming growth factor-β) intracellular signaling, which is responsible for the expression of extracellular matrix genes.
Mycophenolate mofetil (MMF) is one of effective agent for the treatment of chronic graft-versus-host disease. MMF is rapidly absorbed after oral administration and hydrolyzed to the active metabolite, MPA (mycophenolic acid). MPA selectively inhibits inosine monophosphate dehydrogenase, blocking the pathway of purine synthesis in T and B lymphocytes. In this study we will combine MMF and imatinib mesylate to treat steroid-refractory sclerotic/fibrotic type chronic GVHD to see the response rate and to find the safety of combination.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Imatinib mesylate, Mycophenolate mofetil | Experimental | Drug: Imatinib mesylate, Mycophenolate mofetilMMF 15-20mg/kg (Max 1 g) bid + Imatinib mesylate qd * Dose of imatinib : starting dose 260 mg/m2/d (Max. 400 mg) * Imatinib dose adjustment : Dose is adjusted according to the guidelines if there is serious adverse event, toxicity, or intolerance. |
Who may qualify
- Ages
- Up to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (4 listed)
- Patients must have a diagnosis of chronic GVHD with fibrotic/scleroderma-like features. This diagnosis can be made clinically or by histopathology.
- Patients must have active disease with at least one of the following manifestations: skin sclerosis, symptomatic bronchiolitis obliterans, extensive lung fibrosis, pathologically demonstrated visceral fibrotic involvement of the gut.
- Patients with corticosteroid refractory or dependant cGVHD are eligible. Steroid-refractory chronic GVHD is defined as chronic GVHD of sustained severity during the last full month during which the patients received the equivalent of prednisone 0.5 mg/kg or more per day or 1 mg/kg or more every other day.
- Age under 21 years old
Key exclusion criteria (4 listed)
- Patients who have had chemotherapy, radiotherapy within 4 weeks prior to entering the study.
- Patients who have not recovered from adverse events.
- Prior treatment with imatinib mesylate or other tyrosine kinase inhibitor after the date of transplant.
- Patients on pregnancy or lactating
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 |
|---|---|---|
| Imatinib mesylate, Mycophenolate mofetilAlso: Glivec, Cellcept | Drug | Imatinib mesylate, Mycophenolate mofetil |
Primary outcome
Overall (complete and partial) response rate
Time frame: 1 year
Response evaluation will be performed every 3 months during the treatment by comprehensive response criteria based on NIH criteria. The complete and partial response categories apply only to organs that have measurable and reversible GVHD-related abnormalities at baseline. * Complete response (CR): Resolution of all signs and symptoms of chronic GVHD * Partial response (PR) : Improvement (at least 1 clinical score reduction, see Appendix 2) in 1 or more organs of involvement and no evidence of worsening in any organ * Objective response (OR): Either CR or PR
4 secondary outcomes
Evaluate the safety profile of MMF plus imatinib mesylate
Time frame: 1 year
Evaluate the quality of life (QOL)
Time frame: 1 year
Discontinuation of steroid
Time frame: 1 year
Overall survival rate
Time frame: 1 year
Results and safety
The study was stopped early (reason given: New treatment option introduced for patients with the study indication). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Oct 2020.
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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.
Hyoung Jin Kang, MD, Ph.D principal investigator
Seoul National University Children's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Imatinib mesylate, Mycophenolate mofetil in people with Chronic Graft-versus-host Disease, run by Seoul National University Hospital at 1 site in South Korea.
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 4 inclusion and 4 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 23 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Korea. 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 phase mean?
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?
The study was stopped early (reason given: New treatment option introduced for patients with the study indication). 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?
Overall (complete and partial) response rate (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 23 Oct 2020.