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Key inclusion & exclusion criteria
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Inclusion Criteria:
- Patients with SSc as defined by the American College of Rheumatology with diffuse
cutaneous disease (except Group 5) at risk of disease progression
- Patients must have failed a prior >= 4-mponth course of either MMF/Myfortic or
cyclophosphamide before being eligible for the study (determined at >= 1 week before
start of mobilization); "failure" is defined as evidence of disease progression or
absence of improvement; the response prior to MMF of cyclophosphamide will be assessed
by the participating site study rheumatologist
- Patients must meet eligibility in at least 1 of the following 6 groups:
- GROUP 1:
- Patients must have 1) both a and b below; and 2) either c, or d
- a) Diffuse cutaneous scleroderma as defined by skin thickening proximal to
the elbows and knees and/or involving the torso in addition to distal
extremity involvement; a skin score will be obtained but not used to
determine eligibility
- b) Duration of systemic sclerosis =< 7 years from the onset of first
non-Raynaud's symptom; for those patients with disease activity between 5-7
years from the onset of first non-Raynaud's symptom, recent progression or
activity of disease must be documented
- c) Presence of SSc-related pulmonary disease with forced vital capacity
(FVC) < 80% or hemoglobin-adjusted diffusing capacity for carbon monoxide
(DLCO) < 70% of predicted AND evidence of alveolitis or SSc-related
interstitial lung disease by high-resolution chest computed tomography (CT)
scan and/or by bronchoalveolar lavage (BAL) (interstitial lung disease may
be nonspecific interstitial pneumonia [NSIP] or usual interstitial pneumonia
[UIP]; a bronchoalveolar lavage [BAL] should be done to confirm the findings
of alveolitis only if the high resolution CT scan [HRCT] fails to show
findings typically associated with systemic sclerosis changes [ground glass
NSIP, UIP, SSc related interstitial lung disease]); alveolitis by BAL cell
count will be defined based on a BAL cell differential count (> 3%
neutrophils and/or > 2% eosinophils) from any lavaged lobe
- d) History of SSc-related renal disease that may not be active at the time
of screening; stable serum creatinine must be documented for a minimum of 3
months post-renal crisis at the time of the baseline visit; history of
scleroderma hypertensive renal crisis is included in this criterion and is
defined as follows:
- History of new-onset hypertension based on any of the following
(measurements must be repeated and confirmed at least 2 hours apart
within 3 days of first event-associated observation, with a change from
baseline):
- Systolic blood pressure (SBP) >= 140 mmHg
- Diastolic blood pressure (DBP) >= 90 mmHg
- Rise in SBP >= 30 mmHg compared to baseline
- Rise in DBP >= 20 mmHg compared to baseline
- AND one of the following 5 laboratory criteria:
- Increase of >= 50 % above baseline in serum creatinine
- Proteinuria: >= 2+ by dipstick confirmed by
protein:creatinine ratio > 2.5
- Hematuria: >= 2+ by dipstick or > 10 red blood cell
(RBC)s/hematopoietic-promoting factor (HPF) (without
menstruation)
- Thrombocytopenia: < 100,000 platelets/mm^3
- Hemolysis: by blood smear or increased reticulocyte count
- The above definition of SSc hypertensive renal crisis is independent of
whether concomitant anti-hypertensive medications are used
- Subjects who present with solely skin and renal disease in the absence
of other organ involvement, except classic SSc renal crisis as
described above and including non-hypertensive renal crisis, must see a
nephrologist to confirm that their renal disease is secondary to only
SSc
- Note: Subjects may be re-screened if they fail to meet inclusion
criteria on initial evaluation
- GROUP 2:
- Progressive pulmonary disease as defined by a decrease in the FVC or
DLCO-adjusted by 10 or 15 percent or greater, respectively, from a prior FVC or
DLCO-adjusted in the previous 18-month period
- Patients will have diffuse cutaneous disease and may have both FVC and DLCOcorr
>= 70% at screening for the study
- Patients must also have evidence of alveolitis as defined by abnormal chest
computed tomography (CT) or bronchoalveolar lavage (BAL)
- GROUP 3: Diffuse scleroderma with disease duration =< 2 years since development of
first sign of skin thickening plus modified Rodnan skin score >= 25 plus either
- Erythrocyte sedimentation rate (ESR) > 25 mm/1st hour and/or hemoglobin (Hb) < 11
g/dL, not explained by causes other than active scleroderma
- Lung involvement (either FVC or DLCO < 80% and evidence of interstitial lung
disease by CT scan or alveolitis by BAL)
- GROUP 4: Diffuse scleroderma with disease duration =< 2 years and skin score >= 30
- GROUP 5:
- Limited cutaneous scleroderma and SSc-related pulmonary disease with FVC < 80% or
hemoglobin-adjusted DLCO < 70% of predicted
- AND evidence of alveolitis/interstitial lung disease by high-resolution chest CT
scan and/or by BAL (interstitial lung disease may be nonspecific interstitial
pneumonia [NSIP] or usual interstitial pneumonia [UIP]; A bronchoalveolar lavage
[BAL] should be done to confirm the findings of alveolitis only if the high
resolution CT scan [HRCT] fails to show findings typically associated with
systemic sclerosis changes [ground glass, NSIP, UIP, SSc related interstitial
lung disease])
- Alveolitis by BAL cell count will be defined based on a BAL cell differential
count (> 3% neutrophils and/or > 2% eosinophils) from any lavaged lobe
- GROUP 6: Progressive gastrointestinal disease as defin
Age minimum:
N/A
Age maximum:
70 Years
Gender:
All
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Secondary Outcome(s)
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Change in renal function over time
[Time Frame: Annually for 5 years]
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HRQOL as measured by the SGRQ
[Time Frame: Annually for 5 years]
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Infectious complications
[Time Frame: Assessed up to 5 years]
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Overall survival
[Time Frame: Assessed up to 5 years]
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Change in cardiac function
[Time Frame: Year 4]
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Change in renal function over time
[Time Frame: Week 12]
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Improvement in pulmonary function
[Time Frame: Week 12]
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Non-progression mortality
[Time Frame: Assessed up to 5 years]
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Change in renal function over time
[Time Frame: Baseline]
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Health care utilization as assessed by UCSD Healthcare Utilization surveys
[Time Frame: Assessed up to 5 years]
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HRQOL as measured by the PROMIS-29 version 1.0
[Time Frame: Annually for 5 years]
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Improvement in pulmonary function
[Time Frame: 1 month]
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HRQOL as measured by the SF-36
[Time Frame: Annually for 5 years]
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Time of initiation of putative disease-modifying antirheumatic drugs (DMARDS) to modify disease
[Time Frame: After transplant, up to 5 years]
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Time to treatment failure
[Time Frame: The time interval between transplant (day 0) and the initial visit at which death or the qualifying event first occurs, assessed up to 5 years]
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Change in cardiac function
[Time Frame: Year 3]
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Change in cardiac function
[Time Frame: Year 5]
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Change in renal function over time
[Time Frame: Week 26]
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Regimen-related toxicities
[Time Frame: Up to 1 year post-transplant]
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Disease progression
[Time Frame: 6 months and then annually for 5 years]
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Improvement in pulmonary function
[Time Frame: Annually for 5 years]
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Treatment-related mortality
[Time Frame: Day 90]
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All-cause mortality
[Time Frame: Assessed up to 5 years]
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Change in cardiac function
[Time Frame: Year 1]
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Change in cardiac function
[Time Frame: Year 2]
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HRQOL as measured by the SHAQ
[Time Frame: Annually for 5 years]
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Improvement in pulmonary function
[Time Frame: Baseline]
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Improvement in pulmonary function
[Time Frame: Week 26]
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Work productivity Survey (WPS)
[Time Frame: Assessed up to 5 years]
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