Imatinib Mesylate and Mycophenolate Mofetil for Steroid-Refractory Sclerotic/Fibrotic cGVHD in Children

NCT ID: NCT01898377

Last Updated: 2020-10-23

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 9 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-08-31
• Study Completion Date: 2018-02-14

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.

Conditions

Chronic Graft-versus-host Disease

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Imatinib mesylate, Mycophenolate mofetil

Intervention Type: DRUG

Interventions

Imatinib mesylate, Mycophenolate mofetil

Intervention Type: DRUG

Other Intervention Names

Glivec, Cellcept

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

• Maximum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Seoul National University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Hyoung Jin Kang, MD, Ph.D

Role: PRINCIPAL_INVESTIGATOR

Seoul National University Children's Hospital

Locations

Seoul National University Children's Hospital

Seoul, Chongno-gu, South Korea

Countries

South Korea

Other Identifiers

SNUCH-1301

Identifier Type: -

Identifier Source: org_study_id