Imatinib Mesylate Clinical Trial
Official title:
A Phase II Study of Imatinib Mesylate in Children and Adults With Sclerotic Skin Changes of Chronic Graft-Versus-Host Disease
Background:
Chronic graft-versus-host disease (GVHD) is a common complication of stem cell transplant,
resulting from the donor's immune cells attacking the cells of the body of the recipient. One
effect of GVHD is fibrosis (scarring) of the skin that can lead to impaired function,
decreased quality of life and increased risk of death. This is known as sclerotic skin
changes of GVHD, or sclerodermatous graft versus host disease (ScGVHD).
Imatinib mesylate (Gleevec) is a drug that has been approved by the Food and Drug
Administration to treat cancer in humans and fibrosing conditions in animals.
Objectives:
To see if imatinib mesylate can improve ScGVHD and evaluate its effect on other GVHD symptoms
To assess the side effects of imatinib mesylate in patients with GVHD
To evaluate blood, body fluids and tissue samples in patients to try to better understand the
biology of ScGVHD
Eligibility:
Patients 4 years of age and older with ScGVHD
Design:
Initial treatment: Participants take imatinib mesylate tablets once a day for up to 6 months,
as long as their GVHD does not get worse and they do not develop unacceptable side effects of
the drug.
Evaluations: Participants are evaluated at 1, 3 and 6 months at the National Institutes of
Health (NIH) Clinical Center with procedures that may include the following:
Medical history and physical examination
Blood and urine tests
Lung function test
Skin biopsy
Magnetic resonance imaging (MRI) scan
Specialty consultations (e.g., physical or rehabilitative therapy, dentist, eye doctor,
dermatologist)
Electrocardiogram (EKG)
Echocardiogram (ultrasound test of the heart)
Muga scan (nuclear medicine test of the heart)
Quality-of-life questionnaires
Apheresis (procedure for collecting quantities of white blood cells)
Office visits with local physician once a week for 1 month, then once every 2 weeks for 5
months
Followup visits at National Institutes of Health (NIH) every 6 months for 1 year
Continuing treatment: Patients who improve continue to receive imatinib mesylate for up to 6
months after their best response and are followed for up to 2 years. Patients who continue to
respond or who become worse after stopping treatment may receive additional treatment for up
to 2 years.
Background:
Chronic graft versus host disease (cGVHD) is a major complication of allogeneic stem cell
transplant (alloHSCT). The sclerotic skin manifestations of chronic cutaneous GVHD (ScGVHD)
can lead to significant functional impairment and no satisfactory therapy exists to
adequately treat this form of cGVHD.
Imatinib mesylate (Gleevec) is a small molecule tyrosine kinase inhibitor with potent
activity against platelet derived growth factor receptor (PDGFR) signaling, a key cytokine
pathway which has been implicated in fibrotic disease in general, and in extensive cGVHD in
particular.
We hypothesize that treatment with imatinib mesylate will reduce the sclerotic manifestations
of cGVHD as assessed by quantitative range of motion assessment of an affected joint.
Objectives:
Primary Objective:
To investigate whether imatinib mesylate results in clinical improvement in skin fibrosis in
children and adults with ScGVHD using range of motion assessment of affected joints.
To determine if imatinib mesylate 200 mg daily is tolerated by patients with cGVHD.
Secondary Objectives:
To assess toxicity associated with imatinib mesylate in patients with cGVHD.
To establish outcome criteria for the evaluation of ScGVHD using multi-modality objective and
subjective assessments, including magnetic resonance imaging, skin scoring, and patient
self-reported measures.
To evaluate biomarkers of disease activity and correlative response measures to treatment
with imatinib mesylate.
To assess quality of life and functional measures of disease activity and to evaluate changes
through the course of therapy.
To evaluate the response of other organ manifestations affected by cGVHD to treatment with
imatinib mesylate.
To evaluate steady-state pharmacokinetics of imatinib mesylate in the cGVHD patient
population.
Eligibility:
Patients age 4 years of age or older with the diagnosis of ScGVHD.
Design:
This is an open-label, pilot study of imatinib mesylate.
Treatment cycles are 28-day cycles with no rest period between cycles.
A target of 10 evaluable patients will be enrolled on this trial.
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