Clinical trial NCT01898377: 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
Overall status: TERMINATED
Phase: PHASE2
Conditions: Chronic Graft-versus-host Disease
Keywords: Children
Chronic graft-versus-host disease
Lead sponsor: Seoul National University Hospital
Sponsor class: OTHER
First posted: 2013-07-12
Enrollment: 9
Sex: ALL
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Overall (complete and partial) response rate
timeFrame: 1 year
Secondary outcomes:
measure: Evaluate the safety profile of MMF plus imatinib mesylate
timeFrame: 1 year
measure: Evaluate the quality of life (QOL)
timeFrame: 1 year
measure: Discontinuation of steroid
timeFrame: 1 year
measure: Overall survival rate
timeFrame: 1 year
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Seoul National University Children's Hospital
state: Chongno-gu
Study officials:
affiliation: Seoul National University Children's Hospital
name: Hyoung Jin Kang, MD, Ph.D
role: PRINCIPAL_INVESTIGATOR
References: