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Imatinib Mesylate (Gleevec) in the Treatment of Systemic Sclerosis

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ClinicalTrials.gov Identifier: NCT00555581
Recruitment Status : Completed
First Posted : November 8, 2007
Results First Posted : February 6, 2018
Last Update Posted : February 6, 2018
Sponsor:
Collaborator:
Novartis Pharmaceuticals
Information provided by (Responsible Party):
Hospital for Special Surgery, New York

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Systemic Sclerosis
Intervention Drug: Imatinib Mesylate
Enrollment 30
Recruitment Details  
Pre-assignment Details  
Arm/Group Title 400 mg Daily of Imatinib Mesylate
Hide Arm/Group Description

All patients were treated with imatinib mesylate at a target dose of 400 mg daily by mouth for 12 months. Dose modifications and interruptions were made for AE and were recorded. After 12 months of treatment, imatinib was stopped for 3 months. Patients were reassessed and offered entrance to an extension phase of the trial.

Imatinib Mesylate: In initial phase, patients will be treated with Gleevec 400 mg daily for 12 months. In the extension phase, patients will be treated with Gleevec 400 mg daily for 27 months.

Period Title: Overall Study
Started 30
Completed 24
Not Completed 6
Arm/Group Title 400 mg Daily of Imatinib Mesylate
Hide Arm/Group Description

All patients were treated with imatinib mesylate at a target dose of 400 mg daily by mouth for 12 months. Dose modifications and interruptions were made for AE and were recorded. After 12 months of treatment, imatinib was stopped for 3 months. Patients were reassessed and offered entrance to an extension phase of the trial.

Imatinib Mesylate: In initial phase, patients will be treated with Gleevec 400 mg daily for 12 months. In the extension phase, patients will be treated with Gleevec 400 mg daily for 27 months.

Overall Number of Baseline Participants 30
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 30 participants
<=18 years 0
Between 18 and 65 years 29
>=65 years 1
Age, Continuous  
Mean (Full Range)
Unit of measure:  Years
Number Analyzed 30 participants
48
(18 to 71)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 30 participants
Female
24
  80.0%
Male
6
  20.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 30 participants
Hispanic or Latino
4
  13.3%
Not Hispanic or Latino
26
  86.7%
Unknown or Not Reported
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 30 participants
American Indian or Alaska Native
0
   0.0%
Asian
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
4
  13.3%
White
26
  86.7%
More than one race
0
   0.0%
Unknown or Not Reported
0
   0.0%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 30 participants
30
 100.0%
Disease Duration  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 30 participants
Early 2.1  (1.2)
Late 6.1  (1.6)
Anti-Scl70 positive  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 30 participants
9
  30.0%
MRSS at baseline   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 30 participants
30.3  (8.7)
[1]
Measure Description: The Modified Rodnan Skin Score (MRSS) measures dermal skin thickness through the examination of 17 body areas: fingers, hands, forearms, arms, feet, legs, and thighs (in pairs), and face, chest, and abdomen. In each of these areas, the skin score is evaluated by manual palpation. The skin score is 0 for uninvolved skin, 1 for mild thickening, 2 for moderate thickening, and 3 for severe thickening (hidebound skin). The total skin score is the sum of the skin scores of the individual areas. The minimum score is 0 and the maximum score is 51. A higher score indicates greater severity of disease.
1.Primary Outcome
Title Improvement in the Modified Rodnan Skin Score
Hide Description Improvement in the Modified Rodnan Skin Score (MRSS) is measured by Mean change (and 95% Confidence Interval) from Baseline mean to Month 12 mean.Measure Description: The Modified Rodnan Skin Score (MRSS) measures dermal skin thickness through the examination of 17 body areas: fingers, hands, forearms, arms, feet, legs, and thighs (in pairs), and face, chest, and abdomen. The skin score is 0 for uninvolved skin through 3 for severe thickening (hidebound skin). The total skin score is the sum of the skin scores of the individual areas. The minimum score is 0 and the maximum score is 51. A higher score indicates greater severity of disease. The mean change in MRSS represents the average change in total skin score from baseline to month 12.
Time Frame 12 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title 400 mg Daily of Imatinib Mesylate
Hide Arm/Group Description:

All patients were treated with imatinib mesylate at a target dose of 400 mg daily by mouth for 12 months. Dose modifications and interruptions were made for AE and were recorded. After 12 months of treatment, imatinib was stopped for 3 months. Patients were reassessed and offered entrance to an extension phase of the trial.

Imatinib Mesylate: In initial phase, patients will be treated with Gleevec 400 mg daily for 12 months. In the extension phase, patients will be treated with Gleevec 400 mg daily for 27 months.

Overall Number of Participants Analyzed 24
Mean (95% Confidence Interval)
Unit of Measure: units on a scale
-6.6
(-8.7 to -4.5)
2.Secondary Outcome
Title Improvement in Indices of Pulmonary Function Measured by Change in FVC % Predicted
Hide Description This outcome measure includes patients with and without the presence of Interstitial Lung Disease (ILD). Forced vital capacity (FVC) is the amount of air that can be forcibly exhaled from the lungs after taking a deep breath. It is used to determine the severity of lung disease. Improvement in FVC % predicted is measured by Mean change (and 95% Confidence Interval) from Baseline mean to Month 12 mean. Results are compared to the predicted values that are calculated from a patients age, size, weight, and sex. Results are considered normal if FVC is 80 percent or more of the predicted value. Mean change in FVC % predicted is measured by the average change in FVC% percent predicted from baseline to month 12.
Time Frame 12 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title 400 mg Daily of Imatinib Mesylate
Hide Arm/Group Description:

All patients were treated with imatinib mesylate at a target dose of 400 mg daily by mouth for 12 months. Dose modifications and interruptions were made for AE and were recorded. After 12 months of treatment, imatinib was stopped for 3 months. Patients were reassessed and offered entrance to an extension phase of the trial.

Imatinib Mesylate: In initial phase, patients will be treated with Gleevec 400 mg daily for 12 months. In the extension phase, patients will be treated with Gleevec 400 mg daily for 27 months.

Overall Number of Participants Analyzed 22
Mean (95% Confidence Interval)
Unit of Measure: FVC%
6.4
(1.9 to 10.9)
3.Secondary Outcome
Title Improvement in Indices of Pulmonary Function Measured by Change DLCO hb Adj % Predicted
Hide Description This outcome measure includes patients with and without the presence of Interstitial Lung Disease (ILD). Diffusion capacity of the lungs for carbon monoxide (DLCO) measures how much oxygen travels from the alveoli of the lungs to the blood stream. DLCO is adjusted for hemoglobin as small changes in hemoglobin concentration can affect the carbon monoxide transfer. DLCO results are compared to normal values for a patient's height, age, sex, and ethnicity. A DLCO result that is at least 80% of the predicted value is considered normal. Improvement in DLCO hb adj % predicted is measured by Mean change (and 95% Confidence Interval) from Baseline mean to Month 12 mean (the average change in DLCO hb adj% from baseline to month 12).
Time Frame 12 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title 400 mg Daily of Imatinib Mesylate
Hide Arm/Group Description:

All patients were treated with imatinib mesylate at a target dose of 400 mg daily by mouth for 12 months. Dose modifications and interruptions were made for AE and were recorded. After 12 months of treatment, imatinib was stopped for 3 months. Patients were reassessed and offered entrance to an extension phase of the trial.

Imatinib Mesylate: In initial phase, patients will be treated with Gleevec 400 mg daily for 12 months. In the extension phase, patients will be treated with Gleevec 400 mg daily for 27 months.

Overall Number of Participants Analyzed 22
Mean (95% Confidence Interval)
Unit of Measure: DLCO%
5.5
(-1.5 to 12.4)
4.Secondary Outcome
Title Change From Baseline at Month 12 in Short Form-36 (SF-36) Questionnaire:Mental Component Summary
Hide Description The Short Form 36 (SF-36) is a validated 36 item questionnaire which measures quality of life across eight domains: physical functioning, role limitations due to physical health, role limitations due to emotional problems, energy/fatigue, emotional well-being, social functioning, pain, general health. The mental component score is composed of a subset of the 8 health domains. Each component is directly transformed into a 0 to 100 scale on the assumption that each question carries equal weight. A score of 0 is equal to maximum disability, and a score of 100 is equivalent to no disability.The SF-36 mental component can be obtained by looking at the mean average of all the emotionally relevant items. Change in Short Form 36 mental (SF-36 MC) is measured by Mean change (and 95 % Confidence Interval) from Baseline mean to Month 12 mean (the average change in SF-36 mental component from baseline to month 12).
Time Frame 12 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title 400 mg Daily of Imatinib Mesylate
Hide Arm/Group Description:

All patients were treated with imatinib mesylate at a target dose of 400 mg daily by mouth for 12 months. Dose modifications and interruptions were made for AE and were recorded. After 12 months of treatment, imatinib was stopped for 3 months. Patients were reassessed and offered entrance to an extension phase of the trial.

Imatinib Mesylate: In initial phase, patients will be treated with Gleevec 400 mg daily for 12 months. In the extension phase, patients will be treated with Gleevec 400 mg daily for 27 months.

Overall Number of Participants Analyzed 24
Mean (95% Confidence Interval)
Unit of Measure: units on a scale
-6.6
(-12.5 to -0.7)
5.Secondary Outcome
Title Scleroderma Health Assessment Questionnaire Disability Index
Hide Description

The Scleroderma Health Assessment Questionnaire (SHAQ) consist of the Health Assessment Questionnaire (HAQ) and 8 other domains which include scales looking at pain, patient global assessment, vascular, digital ulcers, lung involvement, and gastrointestinal involvement. It addresses scleroderma related manifestations that contribute to disability. It is a quality of life measure. Each question is scored from 0 (without difficulty) to 3 (unable to do). Some domains in the SHAQ are visual analog scales that are measured first and then changed to a 0-3 scale.

The maximum from each category is added together and divided by the number of categories completed. Change in Scleroderma Health Assessment Questionnaire Disability Index (SHAQ-DI) is measured as Mean Change (and 95% Confidence Interval) from Baseline mean to Month 12 mean (the average change in SHAQ-DI from baseline to month 12).

Time Frame 12 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title 400 mg Daily of Imatinib Mesylate
Hide Arm/Group Description:

All patients were treated with imatinib mesylate at a target dose of 400 mg daily by mouth for 12 months. Dose modifications and interruptions were made for AE and were recorded. After 12 months of treatment, imatinib was stopped for 3 months. Patients were reassessed and offered entrance to an extension phase of the trial.

Imatinib Mesylate: In initial phase, patients will be treated with Gleevec 400 mg daily for 12 months. In the extension phase, patients will be treated with Gleevec 400 mg daily for 27 months.

Overall Number of Participants Analyzed 24
Mean (95% Confidence Interval)
Unit of Measure: units on a scale
0.02
(-0.15 to 0.18)
6.Secondary Outcome
Title Change From Baseline at Month 12 in Short Form-36 (SF-36) Questionnaire: Physical Component Summary
Hide Description The Short Form 36 (SF-36) is a 36 item questionnaire which measures quality of life across eight domains: physical functioning, role limitations due to physical health, role limitations due to emotional problems, energy/fatigue, emotional well-being, social functioning, pain, general health. The physical component score is composed of a subset of the 8 health domains.The SF-36 physical component can be obtained by looking at the mean average of all the physically relevant items. Each component is directly transformed into a 0 to 100 scale on the assumption that each question carries equal weight. A score of 0 is equal to maximum disability, and a score of 100 is equivalent to no disability. Change in Short Form 36 physical component (SF-36 PC) is measured by Mean change (and 95 % Confidence Interval) from Baseline mean to Month 12 mean (the average change in SF-36 physical component from baseline to month 12).
Time Frame 12 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title 400 mg Daily of Imatinib Mesylate
Hide Arm/Group Description:

All patients were treated with imatinib mesylate at a target dose of 400 mg daily by mouth for 12 months. Dose modifications and interruptions were made for AE and were recorded. After 12 months of treatment, imatinib was stopped for 3 months. Patients were reassessed and offered entrance to an extension phase of the trial.

Imatinib Mesylate: In initial phase, patients will be treated with Gleevec 400 mg daily for 12 months. In the extension phase, patients will be treated with Gleevec 400 mg daily for 27 months.

Overall Number of Participants Analyzed 24
Mean (95% Confidence Interval)
Unit of Measure: units on a scale
6.8
(1.7 to 15.3)
Time Frame 12 months
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title 400 mg Daily of Imatinib Mesylate
Hide Arm/Group Description

All patients were treated with imatinib mesylate at a target dose of 400 mg daily by mouth for 12 months. Dose modifications and interruptions were made for AE and were recorded. After 12 months of treatment, imatinib was stopped for 3 months. Patients were reassessed and offered entrance to an extension phase of the trial.

Imatinib Mesylate: In initial phase, patients will be treated with Gleevec 400 mg daily for 12 months. In the extension phase, patients will be treated with Gleevec 400 mg daily for 27 months.

All-Cause Mortality
400 mg Daily of Imatinib Mesylate
Affected / at Risk (%)
Total   1/30 (3.33%)    
Show Serious Adverse Events Hide Serious Adverse Events
400 mg Daily of Imatinib Mesylate
Affected / at Risk (%) # Events
Total   12/30 (40.00%)    
Blood and lymphatic system disorders   
Fluid Overload   1/30 (3.33%)  1
Cardiac disorders   
Acute myocardial infarction   1/30 (3.33%)  1
Tachyarrhythmia/cardiomyopathy   1/30 (3.33%)  1
Gastrointestinal disorders   
Acute gastroenteritis   1/30 (3.33%)  1
Partial small bowel obstruction   1/30 (3.33%)  1
Infections and infestations   
C difficile infection   1/30 (3.33%)  2
Infected ulcer   2/30 (6.67%)  2
Injury, poisoning and procedural complications   
Fall   1/30 (3.33%)  1
Renal and urinary disorders   
Haematuria (hospitalisations)   1/30 (3.33%)  7
Rectal proplapse, haemorrhoidal bleed   1/30 (3.33%)  1
Nephrolithiasis   1/30 (3.33%)  1
Respiratory, thoracic and mediastinal disorders   
Pneumonia   2/30 (6.67%)  2
Death (pneumonia)   1/30 (3.33%)  1
Surgical and medical procedures   
Anaemia Blood Transfusion   1/30 (3.33%)  1
Bleeding post renal biopsy (hospitalisation)   1/30 (3.33%)  1
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
400 mg Daily of Imatinib Mesylate
Affected / at Risk (%) # Events
Total   25/30 (83.33%)    
Blood and lymphatic system disorders   
CK elevation   13/30 (43.33%)  13
Light-headedness   3/30 (10.00%)  3
Gastrointestinal disorders   
Pyrosis   7/30 (23.33%)  7
General disorders   
Edema   25/30 (83.33%)  33
Fatigue   18/30 (60.00%)  18
Generalised weakness   5/30 (16.67%)  5
Metabolism and nutrition disorders   
Nausea   22/30 (73.33%)  22
Vomiting   7/30 (23.33%)  7
Weight Loss   5/30 (16.67%)  5
Hypocalcemia   3/30 (10.00%)  3
Musculoskeletal and connective tissue disorders   
Myalgias   21/30 (70.00%)  21
Nervous system disorders   
Headaches   7/30 (23.33%)  7
Reproductive system and breast disorders   
Erectile Dysfunction   2/30 (6.67%)  2
Respiratory, thoracic and mediastinal disorders   
Effusions   3/30 (10.00%)  3
Skin and subcutaneous tissue disorders   
Dry Skin   2/30 (6.67%)  2
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Robert F. Spiera
Organization: Hospital for Special Surgery
Phone: 212-774-2048
Responsible Party: Hospital for Special Surgery, New York
ClinicalTrials.gov Identifier: NCT00555581     History of Changes
Other Study ID Numbers: 27049
First Submitted: November 7, 2007
First Posted: November 8, 2007
Results First Submitted: June 12, 2017
Results First Posted: February 6, 2018
Last Update Posted: February 6, 2018