Cyclophosphamide and rATG With Hematopoietic Stem Cell Support in Systemic Scleroderma

• Register: ClinicalTrials.gov
• Last refreshed on: 19 October 2017
• Main ID: NCT00278525
• Date of registration: 15/01/2006
• Prospective Registration: No
• Primary sponsor: Northwestern University
• Public title: Cyclophosphamide and rATG With Hematopoietic Stem Cell Support in Systemic Scleroderma
• Scientific title: Trial of High Dose Cyclophosphamide and Rabbit Antithymocyte Globulin (rATG) With Hematopoietic Stem Cell Support in Patients With Systemic Scleroderma: A Randomized Trial
• Date of first enrolment: September 2005
• Target sample size: 19
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT00278525
• Study type: Interventional
• Phase: Phase 2

Countries of recruitment

United States

Contacts

• Name: Richard Burt, MD
• Affiliation: Northwestern University

Key inclusion & exclusion criteria

Inclusion Criteria:

- Age 60 year or < 60 year old at the time of pretransplant evaluation.

- An established diagnosis of scleroderma.

- Diffuse cutaneous scleroderma with involvement proximal to the elbow or knee and a
Rodnan score of > 14

AND

Scleroderma with any one of the following:

- Diffusing capacity of the lung for carbon monoxide (DLCO) < 80% of predicted or
decrease in lung function [DLCO, diffusing capacity divided by the alveolar volume
(DLCO/VA) or forced vital capacity (FVC) ] of 10% or more over 12 months.

- Active alveolitis on bronchoalveolar lavage.

- Pulmonary fibrosis or alveolitis on computed tomography (CT) scan or chest x-ray (CXR)
(ground glass appearance of alveolitis).

- Renal disease that is not explained by a bacterial infection or other renal disorders.
(Subjects must have two or more of the following: proteinuria - greater than trace on
dipstick, hematuria - urine blood on dipstick or sediment, hypertension that requires
treatment with anti-hypertensive medications or untreated but with a diastolic blood
pressure (BP) > 95 mm/hg.)

- Abnormal electrocardiogram (EKG) (non-specific ST-T wave abnormalities, low QRS
voltage, or ventricular hypertrophy), or pericardial effusion or pericardial
enhancement on magnetic resonance imaging (MRI)

- Gastrointestinal tract involvement confirmed on radiological study. Radiologic
findings of scleroderma are small bowel radiographs showing thickened folds with
dilated loops, segmentation, and flocculation +/- diverticulae, or pseudodiverticulae.
A hide-bound appearance due to valvulae packing i.e. dilated and crowded circular
folds, may be present. Gastrointestinal (GI) involvement may also be confirmed by
D-xylose malabsorption, patulous esophagus, or esophageal manometry.

OR

As published in NEJM, 2006, 345:25 2655-2709. Limited or diffuse SSL with lung involvement
defined as active alveolitis on bronchoalveolar lavage (BAL) or ground-glass opacity on CT,
a DLCO < 80% predicted or decrease in lung function (DLCO/VA,DLCO, FVC) of 10% or more in
last 12 months.

Exclusion Criteria:

- Poor performance status Eastern Cooperative Oncology Group (ECOG 2) at the time of
entry.

- Significant end organ damage such as:

1. Left Ventricular Ejection Fraction (LVEF) < 40% or deterioration of LVEF during
exercise test on Multiple Gated Acquisition (MUGA) or echocardiogram.

2. Untreated life-threatening arrhythmia.

3. Active ischemic heart disease or heart failure.

4. End-stage lung disease characterized by total lung capacity (TLC) <45% of
predicted value.

5. Pulmonary hypertension (systolic pulmonary arterial pressure > 40 mmHg or mean
pulmonary arterial pressure (PAP) > 25 mmHG measurement by pulmonary arterial
catheter).

6. Serum creatinine > 2.0 mg/dl.

7. Liver cirrhosis, transaminases > 3x of normal limits or bilirubin > 2.0 unless
due to Gilberts disease.

8. Pericardial effusion> 200ml unless successful pericardiocentesis

9. Tricuspid annular peak systolic excursion (TAPSE) = 1.9 cm

10. MRI of heart showing D sign (intraventricular flattering)

- Human immunodeficiency virus (HIV) positive.

- Uncontrolled diabetes mellitus, or any other illness that in the opinion of the
investigators would jeopardize the ability of the patient to tolerate aggressive
treatment.

- Prior history of malignancy except localized basal cell or squamous skin cancer. Other
malignancies for which the patient is judged to be cured by local surgical therapy,
such as (but not limited to) head and neck cancer, or stage I or II breast cancer will
be considered on an individual basis.

- Positive pregnancy test, inability or unable to pursue effective means of birth
control, failure to willingly accept or comprehend irreversible sterility as a side
effect of therapy.

- Psychiatric illness or mental deficiency making compliance with treatment or informed
consent impossible.

- Inability to give informed consent.

- Major hematological abnormalities such as platelet count < 100,000/ul or absolute
neutrophil count (ANC) < 1000/ul.

- Patients with duration of disease > 5 years.

- Exclude if > than 6 prior monthly IV cyclophosphamide treatments.



Age minimum: N/A
Age maximum: 60 Years
Gender: All

Health Condition(s) or Problem(s) studied

SYSTEMIC SCLERODERMA

Intervention(s)

Drug: standard of care

Procedure: stem cell transplantation

Primary Outcome(s)

Time to Treatment Failure [Time Frame: 12 months]

Disease Improvement [Time Frame: 12 months]

Secondary ID(s)

DI Scl.Randomized2004

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 30/04/2014
• URL: https://clinicaltrials.gov/ct2/show/results/NCT00278525