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Imatinib Mesylate (Gleevec) in the Treatment of Systemic Sclerosis

9 januari 2018 uppdaterad av: Hospital for Special Surgery, New York

Phase IIA Study of the Safety and Tolerability of the Use of Imatinib Mesylate (Gleevec) in the Treatment of Systemic Sclerosis

The purpose of this study is to assess the safety and tolerability of imatinib mesylate (Gleevec) in patients with systemic sclerosis (scleroderma). Gleevec is a medication already FDA approved for the treatment of chronic myelogenous leukemia (CML), gastrointestinal stromal tumors (GIST), dermatofibrosarcoma protuberans tumors, Philadelphia chromosome-positive acute lymphoblastic leukemia, hypereosinophilic syndrome, and aggressive systemic mastocytosis. In-vitro studies have suggested that imatinib may inhibit collagen production by scleroderma fibroblasts, and in mouse models of fibrosis imatinib has been shown to decrease skin thickness.

This is a Phase IIa, single center, prospective open label clinical trial of Gleevec in patients with systemic sclerosis. All patients will be treated with active drug for 12 months. The primary objective of this study will be to determine the safety and tolerability of Gleevec in patients with systemic sclerosis, but important secondary outcomes of relevance will be improvement in disease status as defined by skin scores and indices of pulmonary function.

Patients who complete the initial phase (described above) of the study will be eligible to participate in an extension phase. The purpose of the extension phase of the study is to give patients who participated in the phase IIa clinical trial of Gleevec at the Hospital for Special Surgery the opportunity to continue Gleevec treatment if both the treating physicians and the patient are in agreement that Gleevec had acceptable safety and tolerability, as well as possible efficacy during the initial year of therapy.

Studieöversikt

Status

Avslutad

Betingelser

Intervention / Behandling

Detaljerad beskrivning

Further description of extension phase:

Patients will first be evaluated for inclusion in the extension phase of the study at either the follow-up visit following three month withdrawal from Gleevec treatment or at the visit after the follow-up visit. Patients can undergo evaluation for inclusion in the extension phase up to six months following their completion of the initial one year trial. All patients evaluated for inclusion in the extension phase will sign a new informed consent form detailing the purpose and procedures associated with the extension phase at the initial visit. After the initial visit, patients who meet inclusion criteria will be required to undergo evaluation every three months for the 27 months following initiation of treatment, or more frequently if deemed clinically necessary. Treatment will consist of Gleevec, at doses ranging from 100 to 400 mg daily (100 mg pills will be distributed for oral administration). At each study visit, a history and physical exam will be performed and urine and blood tests will be conducted for disease activity and organ function. Additional blood for research may also be collected at study visits. The Modified Rodnan Skin Score will be measured to assess the degree of skin involvement associated with the patient's disease. Patients will also continue to complete questionnaires about their ability to function and quality of life.

Patients will be financially responsible for all professional and clinical services, as well as all laboratory and diagnostic tests, associated with the extension phase of the study. All co-pays, deductibles and co-insurances will be paid by the participants. Any additional costs for parking and travel the patients incur as a result of participating in the extension phase will not be reimbursed by the study. Novartis Pharmaceuticals will donate drug supply.

Studietyp

Interventionell

Inskrivning (Faktisk)

30

Fas

  • Fas 2

Kontakter och platser

Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.

Studieorter

  • Förenta staterna
    • New York
      • New York, New York, Förenta staterna, 10021
        • Hospital For Special Surgery

Deltagandekriterier

Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.

Urvalskriterier

Åldrar som är berättigade till studier

18 år och äldre (Vuxen, Äldre vuxen)

Tar emot friska volontärer

Nej

Kön som är behöriga för studier

Allt

Beskrivning

Inclusion Criteria:

  1. Age greater than or equal to eighteen years.
  2. Clinical diagnosis of diffuse systemic sclerosis by ACR criteria, with a stable modified Rodnan skin score in the one month preceding introduction of oral Gleevec therapy. The modified Rodnan skin score must be greater than or equal to sixteen at screening and initiation of therapy.
  3. Disease duration of less than or equal to 10 years.
  4. Estimated ejection fraction of greater than 50% by echocardiography

Exclusion Criteria:

  1. Inability to render informed consent in accordance with institutional guidelines.
  2. Disease duration of greater than 10 years.
  3. Patients with mixed connective tissue disease or "overlap" (i.e. those who satisfy more than one set of ACR criteria for a rheumatic disease.)
  4. Ongoing treatment with other immunosuppressive therapies including cyclophosphamide, azathioprine, mycophenolic acid, methotrexate, or cyclosporine, or use of those medications within 3 months of trial entry.
  5. Concurrent serious medical condition which in the opinion of the investigator makes the patient inappropriate for this study such as uncontrollable CHF, arrhythmia, severe pulmonary or systemic hypertension, severe GI involvement, serum creatinine of greater than 2.0, active infection, severe diabetes, unstable atherosclerotic cardiovascular disease, malignancy, HIV, or severe peripheral vascular disease.
  6. The use of other anti-fibrotic agents including colchicine, D-penicillamine, minocycline, or Type 1 oral Collagen in the three months prior to enrollment.
  7. Limited scleroderma.
  8. Systemic sclerosis-like illness associated with environmental or ingested agents such as toxic rapeseed oil, vinyl chloride, or bleomycin.
  9. A positive pregnancy at entry into this study. Men and women with reproductive potential will be required to use effective means of contraception through the course of the study.
  10. Use in the prior month of corticosteroids at doses exceeding the equivalent of prednisone 10 mg daily. Use of corticosteroid at < 10 mg of prednisone can continue but not be increased during the course of the study.
  11. Participation in another clinical research study involving the evaluation of another investigational drug within ninety days of entry into this study.
  12. The presence of severe lung disease as defined by a diffusion capacity of less than 30% of predicted.

Studieplan

Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.

Hur är studien utformad?

Designdetaljer

  • Primärt syfte: Behandling
  • Tilldelning: N/A
  • Interventionsmodell: Enskild gruppuppgift
  • Maskning: Ingen (Open Label)

Vapen och interventioner

Deltagargrupp / Arm
Intervention / Behandling
Experimentell: 400 mg daily of Imatinib Mesylate
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.
Läkemedel: 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.

Vad mäter studien?

Primära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Improvement in the Modified Rodnan Skin Score
Tidsram: 12 months
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.
12 months

Sekundära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Improvement in Indices of Pulmonary Function Measured by Change in FVC % Predicted
Tidsram: 12 months
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.
12 months
Improvement in Indices of Pulmonary Function Measured by Change DLCO hb Adj % Predicted
Tidsram: 12 months
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).
12 months
Change From Baseline at Month 12 in Short Form-36 (SF-36) Questionnaire:Mental Component Summary
Tidsram: 12 months
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).
12 months
Scleroderma Health Assessment Questionnaire Disability Index
Tidsram: 12 months

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).
12 months
Change From Baseline at Month 12 in Short Form-36 (SF-36) Questionnaire: Physical Component Summary
Tidsram: 12 months
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).
12 months

Samarbetspartners och utredare

Det är här du hittar personer och organisationer som är involverade i denna studie.

Sponsor

Hospital for Special Surgery, New York

Samarbetspartners

Novartis Pharmaceuticals

Utredare

  • Huvudutredare: Robert Spiera, MD, Hospital for Special Surgery, New York

Publikationer och användbara länkar

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Allmänna publikationer

Användbara länkar

Studieavstämningsdatum

Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.

Studera stora datum

Studiestart

1 augusti 2007

Primärt slutförande (Faktisk)

1 december 2011

Avslutad studie (Faktisk)

1 december 2011

Studieregistreringsdatum

Först inskickad

7 november 2007

Först inskickad som uppfyllde QC-kriterierna

7 november 2007

Första postat (Uppskatta)

8 november 2007

Uppdateringar av studier

Senaste uppdatering publicerad (Faktisk)

6 februari 2018

Senaste inskickade uppdateringen som uppfyllde QC-kriterierna

9 januari 2018

Senast verifierad

1 januari 2018

Mer information

Termer relaterade till denna studie

Nyckelord

Ytterligare relevanta MeSH-villkor

Andra studie-ID-nummer

  • 27049

Denna information hämtades direkt från webbplatsen clinicaltrials.gov utan några ändringar. Om du har några önskemål om att ändra, ta bort eller uppdatera dina studieuppgifter, vänligen kontakta register@clinicaltrials.gov. Så snart en ändring har implementerats på clinicaltrials.gov, kommer denna att uppdateras automatiskt även på vår webbplats .

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