Back to resultsImatinib Mesylate and Mycophenolate Mofetil for Steroid-Refractory Sclerotic/Fibrotic cGVHD in Children
Primary Purpose
Chronic Graft-versus-host Disease
Status
Terminated
Phase
Phase 2
Locations
Korea, Republic of
Study Type
Interventional
Intervention
Imatinib mesylate, Mycophenolate mofetil
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Graft-versus-host Disease focused on measuring Children, Chronic graft-versus-host disease
Eligibility Criteria
Inclusion criteria
- 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
Exclusion criteria
- 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
Sites / Locations
- Seoul National University Children's Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Imatinib mesylate, Mycophenolate mofetil
Arm Description
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.
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
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)
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.
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.
Overall survival rate
For survival outcome, Kaplan-Meier method will be used for estimation.
Full Information
NCT ID
NCT01898377
First Posted
June 5, 2013
Last Updated
October 21, 2020
Sponsor
Seoul National University Hospital
1. Study Identification
Unique Protocol Identification Number
NCT01898377
Brief Title
Imatinib Mesylate and Mycophenolate Mofetil for Steroid-Refractory Sclerotic/Fibrotic cGVHD in Children
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
Study Type
Interventional
2. Study Status
Record Verification Date
October 2020
Overall Recruitment Status
Terminated
Why Stopped
New treatment option introduced for patients with the study indication
Study Start Date
August 2013 (undefined)
Primary Completion Date
February 14, 2018 (Actual)
Study Completion Date
February 14, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Seoul National University Hospital
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Graft-versus-host Disease
Keywords
Children, Chronic graft-versus-host disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
9 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Imatinib mesylate, Mycophenolate mofetil
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Imatinib mesylate, Mycophenolate mofetil
Other Intervention Name(s)
Glivec, Cellcept
Primary Outcome Measure Information:
Title
Overall (complete and partial) response rate
Description
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
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Evaluate the safety profile of MMF plus imatinib mesylate
Description
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)
Time Frame
1 year
Title
Evaluate the quality of life (QOL)
Description
The assessment of QOL will be performed at baseline and every 3 months till 1 year with Lee cGVHD Symptom Scale.
Time Frame
1 year
Title
Discontinuation of steroid
Description
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.
Time Frame
1 year
Title
Overall survival rate
Description
For survival outcome, Kaplan-Meier method will be used for estimation.
Time Frame
1 year
10. Eligibility
Sex
All
Maximum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria
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
Exclusion criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hyoung Jin Kang, MD, Ph.D
Organizational Affiliation
Seoul National University Children's Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Seoul National University Children's Hospital
City
Seoul
State/Province
Chongno-gu
Country
Korea, Republic of
12. IPD Sharing Statement
Learn more about this trial
Imatinib Mesylate and Mycophenolate Mofetil for Steroid-Refractory Sclerotic/Fibrotic cGVHD in Children
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