Autologous Stem Cell Systemic Sclerosis Immune Suppression Trial

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT01445821
• Date of registration: 29/09/2011
• Prospective Registration: No
• Primary sponsor: Northwestern University
• Public title: Autologous Stem Cell Systemic Sclerosis Immune Suppression Trial DIScl2011
• Scientific title: Randomized Study of Different Non-myeloablative Conditioning Regimens With Hematopoietic Stem Cell Support in Patients With Scleroderma (Autologous Systemic Sclerosis Immune Suppression Trial - II ASSIST-IIb)
• Date of first enrolment: September 15, 2011
• Target sample size: 44
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/show/NCT01445821
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 3

Countries of recruitment

United States

Contacts

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

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Age 17- 60 years old at the time of pretransplant evaluation

2. An established diagnosis of scleroderma

3. Diffuse cutaneous scleroderma with involvement proximal to the elbow or knee and a
Rodnan score (see Appendix V) of > 14 AND

Scleroderma with any one of the following:

1. DLCO < 80% of predicted or decrease in lung function (DLCO, DLCO/VA or FVC) of
10% or more over 12 months.

2. Pulmonary fibrosis or alveolitis on CT scan or chest X-ray (CXR) (ground glass
appearance of alveolitis).

3. Abnormal EKG [non-specific ST-segment and T-wave (ST-T) (pattern in
electrocardiogram) wave abnormalities, low QRS (a pattern seen in an
electrocardiogram that indicates the pulses in a heart beat and their duration)
voltage, or ventricular hypertrophy], or pericardial effusion or pericardial
enhancement on MRI

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

OR

4. As published in New England Journal of Medicine (NEJM), 2006, 345:25 2655-2709.
Limited or diffuse Systemic Sclerosis with (SSCL) 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:

1. Significant end organ damage such as:

1. Left Ventricular Function (LVEF) < 40% on echocardiogram.

2. Untreated life-threatening arrhythmia.

3. Active ischemic heart disease or heart failure.

4. End-stage lung disease characterized by TLC<45% of predicted value, or DLCO
hemoglobin corrected < 30% predicted .

5. Pulmonary arterial hypertension defined on right heart catheterization as:

1. a resting Mean Pulmonary Artery Pressure (mPAP) > 25 mmHg;

2. a mPAP > 30 mmHg following a 500-1000 ml normal saline bolus;

3. pulmonary vascular resistance (PVR) > 240 dynes*s/cm5 (> 3 Wood units) ; or

4. a decrease in cardiac output with fluid challenge (500 - 1000 cc Normal
Saline (NS) in 10 minutes) If fluid challenge cannot be done because right
atrial (RA) pressure > 12mm Hg or pulmonary capillary wedge pressure (PCWP)
> 15 m Hg at rest or must be stopped due to safety concerns, patient is
excluded as candidate.

6. Serum creatinine > 1.4 mg/dl.

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

8. Pericardial effusion > 1 cm on cardiac MRI unless successful pericardiocentesis
has been performed

9. Occult or clinical constrictive pericarditis

10. On echocardiogram tricuspid annular peak systolic excursion (TAPSE) = 1.8 cm or,
grade II or worse Right Ventricular (RV) or Left Ventricular (LV) diastolic
dysfunction

11. On cardiac MRI, a diastolic septal bounce or diastolic septal flattering
(D-sign), or diffuse myocardial gadolinium enhancement, or diffuse hypokinesis
(patchy late gadolinium myocardial enhancement are not exclusion criteria)

12. Ventricular tachycardia (sustained or non-sustained, multifocal or unifocal) on
EKG or 24 hour Holter

2. HIV positive.

3. 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.

4. Prior history of malignancy

5. 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.

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

7. Inability to give informed consent.

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

9. Hepatitis B or C positive



Age minimum: 17 Years
Age maximum: 60 Years
Gender: All

Health Condition(s) or Problem(s) studied

Scleroderma, Systemic

Intervention(s)

Drug: Methylprednisolone

Drug: Fludarabine

Drug: Filgrastim

Biological: Peripheral Blood Stem Cells

Drug: Cyclophosphamide

Drug: rATG

Drug: Mesna

Primary Outcome(s)

Number of Participants With Treatment Failure [Time Frame: up to and post 12 months of treatment]

Secondary Outcome(s)

Survival of Treatment [Time Frame: up to 12 months post treatment]

Secondary ID(s)

ASSIST IIb

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 23/07/2020
• URL: https://clinicaltrials.gov/ct2/show/results/NCT01445821