Imatinib Mesylate and Mycophenolate Mofetil for Steroid-Refractory Sclerotic/Fibrotic cGVHD in Children
- Conditions
- Chronic Graft-versus-host Disease
- Interventions
- Registration Number
- NCT01898377
- Lead Sponsor
- Seoul National University Hospital
- 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 9
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Imatinib mesylate, Mycophenolate mofetil Imatinib mesylate, Mycophenolate mofetil 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.
- Primary Outcome Measures
Name Time Method Overall (complete and partial) response rate 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
- Secondary Outcome Measures
Name Time Method Overall survival rate 1 year For survival outcome, Kaplan-Meier method will be used for estimation.
Evaluate the safety profile of MMF plus imatinib mesylate 1 year 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)Discontinuation of steroid 1 year * 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.Evaluate the quality of life (QOL) 1 year The assessment of QOL will be performed at baseline and every 3 months till 1 year with Lee cGVHD Symptom Scale.
Trial Locations
- Locations (1)
Seoul National University Children's Hospital
🇰🇷Seoul, Chongno-gu, Korea, Republic of