Imatinib Mesylate and Mycophenolate Mofetil for Steroid-Refractory Sclerotic/Fibrotic cGVHD in Children
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|ClinicalTrials.gov Identifier: NCT01898377|
Recruitment Status : Active, not recruiting
First Posted : July 12, 2013
Last Update Posted : April 8, 2019
|Condition or disease||Intervention/treatment||Phase|
|Chronic Graft-versus-host Disease||Drug: Imatinib mesylate, Mycophenolate mofetil||Phase 2|
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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||28 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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 Start Date :||August 2013|
|Actual Primary Completion Date :||July 2018|
|Estimated Study Completion Date :||July 2019|
Experimental: Imatinib mesylate, Mycophenolate mofetil
MMF 15-20mg/kg (Max 1 g) bid + Imatinib mesylate qd
Drug: Imatinib mesylate, Mycophenolate mofetil
Other Name: Glivec, Cellcept
- 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
- Evaluate the safety profile of MMF plus imatinib mesylate [ Time Frame: 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)
- Evaluate the quality of life (QOL) [ Time Frame: 1 year ]The assessment of QOL will be performed at baseline and every 3 months till 1 year with Lee cGVHD Symptom Scale.
- Discontinuation of steroid [ Time Frame: 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.
- Overall survival rate [ Time Frame: 1 year ]For survival outcome, Kaplan-Meier method will be used for estimation.
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): NCT01898377
|Korea, Republic of|
|Seoul National University Children's Hospital|
|Seoul, Chongno-gu, Korea, Republic of|
|Principal Investigator:||Hyoung Jin Kang, MD, Ph.D||Seoul National University Children's Hospital|