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NCT00702689

Imatinib Mesylate to Treat Skin Changes in Patients With Chronic Graft-Versus-Host Disease

Completed Phase 2 Results posted Last updated 30 March 2020
What this trial tests

Phase 2 trial testing Gleevec, STI571(Imatinib Mesylate) in Sclerotic Graft Versus Host Disease in 20 participants. Completed in 26 February 2020.

Timeline
15 December 2008
Primary endpoint
18 May 2011
26 February 2020

Quick facts

Lead sponsorNational Cancer Institute (NCI)
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment20
Start date15 December 2008
Primary completion18 May 2011
Estimated completion26 February 2020
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

National Cancer Institute (NCI)

Who can join

4 and older, any sex, with Sclerotic Graft Versus Host Disease or Imatinib Mesylate. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percent Change in Absolute Range of Motion (ROM) From Baseline to 6 Months Primary · 6 months

A change in ROM is 25% or greater from baseline. A partial response required improvement in 25% or more in ROM. Progression required 25% or greater loss of ROM.Patients with negative values in the Table are those who lost ROM. Percent improvement in ROM for 1-3 target joints. For patients with \>1 target joint, the average ROM improvement was calculated. The average percentage change in ROM deficit from baseline to 6 months was obtained based on the number of degrees of ROM change (6 months)/total ROM deficit (baseline) at each joint.

Pt 2 6mo response% change in deficit from baseline
GroupValue95% CI
Imatinib Mesylate in Patients With cGVHD94
Pt 7 6mo response% change in deficit from baseline
GroupValue95% CI
Imatinib Mesylate in Patients With cGVHD35
Pt 8 6mo response% change in deficit from baseline
GroupValue95% CI
Imatinib Mesylate in Patients With cGVHD16
Pt10 6mo response% change in deficit from baseline
GroupValue95% CI
Imatinib Mesylate in Patients With cGVHD21
Pt12 6mo response% change in deficit from baseline
GroupValue95% CI
Imatinib Mesylate in Patients With cGVHD16
Pt13 6mo response% change in deficit from baseline
GroupValue95% CI
Imatinib Mesylate in Patients With cGVHD61
Pt14 6mo response% change in deficit from baseline
GroupValue95% CI
Imatinib Mesylate in Patients With cGVHD27
Pt15 6mo response% change in deficit from baseline
GroupValue95% CI
Imatinib Mesylate in Patients With cGVHD22
Primary Range of Motion (ROM) Response Primary · 6 months

Progressive disease is defined as joint ROM: decrease of \>25% in composite ROM score on 2 consecutive evaluations at least 2 weeks apart, but not greater than 4 weeks apart or steroid pulse: \>1 steroid pulse per 3 month period if administered for sclerotic-type chronic graft versus host disease (ScGVHD). Response is joint ROM: increase of \>25% in composite ROM score. Maximal response is a response with no further improvement over 2 sequential 3-month evaluations. Stable disease does not meet the criteria for progression, response, or maximal response.

Partial Response
GroupValue95% CI
Imatinib Mesylate in Patients With cGVHD5
Stable Disease
GroupValue95% CI
Imatinib Mesylate in Patients With cGVHD7
Progressive Disease
GroupValue95% CI
Imatinib Mesylate in Patients With cGVHD2
Number of Participants With Adverse Events Secondary · Date treatment consent signed to date off study, approximately, 41 months, 27 days

Here is the number of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one

GroupValue95% CI
Imatinib Mesylate in Patients With cGVHD20
Average Percentage Change in Range of Motion (ROM) Deficit Secondary · 6 months

One or more joints were assessed for ROM deficit by a physiatrist with expertise in graft versus host disease and joint ROM.

GroupValue95% CI
Imatinib Mesylate in Patients With cGVHD24.215.5 – 30.5
Total Skin Score at Baseline and 6 Months Secondary · Baseline and 6 Months

Total skin score was graded by the National Institutes of Health Consensus Criteria. Skin score was calculated by dividing the total score by seven domains (skin, eye, oral, joint, gastrointestinal, hepatic, pulmonary) in men and 8 domains in women (previous domains noted plus gynecologic). Total skin score is a percentage of body surface area (BSA) involvement (range 0-100%). It was calculated from the sum of moveable body surface BSA and non-moveable BSA. Higher numbers = greater body surface area affected.

Patient # 2 - Baseline
GroupValue95% CI
Imatinib Mesylate in Patients With cGVHD66.6
Patient # 2 - 6 months
GroupValue95% CI
Imatinib Mesylate in Patients With cGVHD54
Patient # 3 - Baseline
GroupValue95% CI
Imatinib Mesylate in Patients With cGVHD43.38
Patient # 3 - 6 months
GroupValue95% CI
Imatinib Mesylate in Patients With cGVHDNA
Patient # 7 - Baseline
GroupValue95% CI
Imatinib Mesylate in Patients With cGVHD66.24
Patient # 7 - 6 months
GroupValue95% CI
Imatinib Mesylate in Patients With cGVHD55.53
Patient # 8 - Baseline
GroupValue95% CI
Imatinib Mesylate in Patients With cGVHD53.1
Patient # 8 - 6 months
GroupValue95% CI
Imatinib Mesylate in Patients With cGVHD55.26
Total Chronic Graft Versus Host Disease (cGVHD) Provider Global Rating Score at Baseline and 6 Months Secondary · Baseline and 6 months

The provider global rating is a physician impression of severity of cGVHD symptoms from a scale of zero (no symptoms) to 10 (most severe GVHD symptoms possible).

Patient #2 at Baseline
GroupValue95% CI
Imatinib Mesylate in Patients With cGVHD5
Patient #2 at 6 Months
GroupValue95% CI
Imatinib Mesylate in Patients With cGVHD4
Patient #3 at Baseline
GroupValue95% CI
Imatinib Mesylate in Patients With cGVHD3
Patient #3 at 6 Months
GroupValue95% CI
Imatinib Mesylate in Patients With cGVHDNA
Patient #7 at Baseline
GroupValue95% CI
Imatinib Mesylate in Patients With cGVHD6
Patient #7 at 6 Months
GroupValue95% CI
Imatinib Mesylate in Patients With cGVHD8
Patient #8 at Baseline
GroupValue95% CI
Imatinib Mesylate in Patients With cGVHD6
Patient #8 at 6 Months
GroupValue95% CI
Imatinib Mesylate in Patients With cGVHD7
Lung Function Score at Baseline and 6 Months Secondary · Baseline and 6 Months

Lung function was graded by the National Institutes of Health Chronic Graft Versus Host Disease organ response criteria. The Lung function score = forced expiratory volume 1 (FEV1) score + carbon monoxide diffusing capacity (DLCO) score, with a possible range of 2 (better outcome)-12 (worst outcome). The percent predicted FEV1 and DLCO (adjusted for hematocrit but not alveolar volume) should be converted to a numeric score as follows: \>80% =1; 70-79% = 2; 60-69% = 3; 50-59% = 4; 40-49% = 5; \<40% = 6.

Patient #2 at Baseline
GroupValue95% CI
Imatinib Mesylate in Patients With cGVHD2
Patient #2 at 6 Months
GroupValue95% CI
Imatinib Mesylate in Patients With cGVHD2
Patient #3 at Baseline
GroupValue95% CI
Imatinib Mesylate in Patients With cGVHD9
Patient #3 at 6 Months
GroupValue95% CI
Imatinib Mesylate in Patients With cGVHDNA
Patient #7 at Baseline
GroupValue95% CI
Imatinib Mesylate in Patients With cGVHD3
Patient #7 at 6 Months
GroupValue95% CI
Imatinib Mesylate in Patients With cGVHD8
Patient #8 at Baseline
GroupValue95% CI
Imatinib Mesylate in Patients With cGVHD5
Patient #8 at 6 Months
GroupValue95% CI
Imatinib Mesylate in Patients With cGVHD6
Change in Immunosuppression Secondary · 6 months

Change in immunosuppression was defined by an increase or decrease in steroid use form baseline.

↓ Pred 20 mg everyday (qd )to 5 mg every other day
GroupValue95% CI
Imatinib Mesylate in Patients With cGVHD1
↓ MPred 16 mg every other day(qod) to 4 mg qod
GroupValue95% CI
Imatinib Mesylate in Patients With cGVHD1
↓ Pred:24mg every day(qd) to 20mg qd
GroupValue95% CI
Imatinib Mesylate in Patients With cGVHD1
No change
GroupValue95% CI
Imatinib Mesylate in Patients With cGVHD5
↓ Tacro 2mg every am 1.5mg every pm to .5mg bid
GroupValue95% CI
Imatinib Mesylate in Patients With cGVHD1
Pred↓ 25mg qd to 15mg qd;Tacro↓ 2mg bid to 1mg bid
GroupValue95% CI
Imatinib Mesylate in Patients With cGVHD1
Pred↓ 2.5mg qd to 2.5mg every other day
GroupValue95% CI
Imatinib Mesylate in Patients With cGVHD1
↓ Siro:2mg qd to 1 mg qd
GroupValue95% CI
Imatinib Mesylate in Patients With cGVHD1

Adverse events — posted to ClinicalTrials.gov

Time frame: Date treatment consent signed to date off study, approximately, 41 months, 27 days.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Imatinib Mesylate in Patients With cGVHD
Serious: 5/20 (25%)
Deaths: 0/20

Serious adverse events (13 terms)

ReactionSystemImatinib Mesylate in Patie…
Dyspnea (shortness of breath)Respiratory, thoracic and mediastinal disorders
Pulmonary/Upper Respiratory - Other (Specify, Pulmonary edema)Respiratory, thoracic and mediastinal disorders
Edema::head and neckGeneral disorders
Edema: limbGeneral disorders
Edema:: trunk/genitalGeneral disorders
HypertensionVascular disorders
HypoxiaRespiratory, thoracic and mediastinal disorders
Infection with unknown ANC::Lung (pneumonia)Infections and infestations
Muscle weakness, generalized or specific area (not due to neuropathy)::Whole body/generalizedMusculoskeletal and connective tissue disorders
NauseaGastrointestinal disorders
Pain::Head/headacheNervous system disorders
Pleural effusion (non-malignant)Respiratory, thoracic and mediastinal disorders
VomitingGastrointestinal disorders
Other adverse events (56 terms — click to expand)

ReactionSystemImatinib Mesylate in Patie…
Phosphate, serum-low (hypophosphatemia)Metabolism and nutrition disorders
NauseaGastrointestinal disorders
Fatigue (asthenia, lethargy, malaise)General disorders
DiarrheaGastrointestinal disorders
HemoglobinInvestigations
Pain::MuscleMusculoskeletal and connective tissue disorders
AST, SGOT(serum glutamic oxaloacetic transaminase)Investigations
CPK (creatine phosphokinase)Investigations
Pain::Head/headacheNervous system disorders
ALT, SGPT (serum glutamic pyruvic transaminase)Investigations
Albumin, serum-low (hypoalbuminemia)Metabolism and nutrition disorders
CoughRespiratory, thoracic and mediastinal disorders
TinnitusEar and labyrinth disorders
VomitingGastrointestinal disorders
Allergic rhinitis (including sneezing, nasal stuffiness, postnasal drip)Immune system disorders
Calcium, serum-high (hypercalcemia)Metabolism and nutrition disorders
Edema::head and neckGeneral disorders
Edema: limbGeneral disorders
Potassium, serum-high (hyperkalemia)Metabolism and nutrition disorders
Rash/desquamationSkin and subcutaneous tissue disorders
Constitutional Symptoms-Other (Specify, cold intolerance; sleep walking)General disorders
CreatinineInvestigations
DizzinessNervous system disorders
DyspneaRespiratory, thoracic and mediastinal disorders
Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L)General disorders
Flu-like symptomsGeneral disorders
Sodium, serum-low (hyponatremia)Metabolism and nutrition disorders
Alkaline phosphataseInvestigations
AnorexiaMetabolism and nutrition disorders
BronchospasmRespiratory, thoracic and mediastinal disorders
Bruising (in absence of Grade 3 or 4 thrombocytopenia)Injury, poisoning and procedural complications
ConstipationGastrointestinal disorders
Dermatology/Skin-Other (Specify, intermt. bilateral hands & L. hip)Skin and subcutaneous tissue disorders
Dry skinSkin and subcutaneous tissue disorders
FlushingVascular disorders
Glucose, serum-low (hyperglycemia)Metabolism and nutrition disorders
Heartburn/dyspepsiaGastrointestinal disorders
HypertensionVascular disorders
Infection with normal ANC or Grade 1 or 2 neutrophils::otitis externaInfections and infestations
InsomniaPsychiatric disorders

Most-reported serious reactions: Dyspnea (shortness of breath), Pulmonary/Upper Respiratory - Other (Specify, Pulmonary edema), Edema::head and neck, Edema: limb, Edema:: trunk/genital, Hypertension, Hypoxia, Infection with unknown ANC::Lung (pneumonia).

Data from ClinicalTrials.gov NCT00702689 adverse events section.

Sponsor's own description

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.

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Kinase Inhibition as Treatment for Acute and Chronic Graft-<i>Versus</i>-Host Disease.
    Braun LM, Zeiser R. · · 2021 · cited 35× · PMID 34868001 · DOI 10.3389/fimmu.2021.760199
  2. Graft Versus Host Disease Clinical Trials: Is it Time for Patients Centered Outcomes to Be the Primary Objective?
    Shaw BE. · · 2019 · cited 8× · PMID 30637541 · DOI 10.1007/s11899-019-0494-x
  3. Motor ability, function, and health-related quality of life as correlates of symptom burden in patients with sclerotic chronic graft-versus-host disease receiving imatinib mesylate.
    Rosenthal EA, Ho PS, Joe GO, Mitchell SA, et al · · 2020 · cited 3× · PMID 31811481 · DOI 10.1007/s00520-019-05207-z

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