Autologous Stem Cell Transplantation in Patients With Systemic Sclerosis

• Register: ClinicalTrials.gov
• Last refreshed on: 18 September 2023
• Main ID: NCT03630211
• Date of registration: 07/08/2018
• Prospective Registration: No
• Primary sponsor: Paul Szabolcs
• Public title: Autologous Stem Cell Transplantation in Patients With Systemic Sclerosis SSc
• Scientific title: Autologous Stem Cell Transplantation With CD34-Selected Peripheral Blood Stem Cells (PBSC) in Patients With Treatment Resistant Systemic Sclerosis (SSc)
• Date of first enrolment: July 31, 2018
• Target sample size: 8
• Recruitment status: Recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT03630211
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

United States

Contacts

• Name: Paul Szabolcs, MD

• Name: Paul Szabolcs, MD
• Affiliation: University of Pittsburgh

Key inclusion & exclusion criteria

Cohort 1: Children, Adolescents and Young Adults (Cohort 1)

Inclusion:

Individuals must meet all the following criteria to be eligible for this study.

1. Patient, parent, or legal guardian must have given written informed consent. For
patients = 168 years of age who are developmentally able, assent or affirmation will
be obtained.

2. Age 8-24, inclusive, at time of consent.

3. Diagnosed with Systemic Sclerosis (SSc) at the age of =19.

4. Failure to respond, specifically no improvement or progression of disease, to at least
2 disease-modifying antirheumatic drugs (DMARDS) within 12 months of consent with any
of the following conditions:

1. Progression of skin thickening over the past 6 months or Modified Rodnan skin
score (mRSS) = 20

2. Progression of ILD within 18 months prior to consent. Progression to be
determined by either of the following:

- CT scan showing increased ground glass opacities or reticulations OR

- Pulmonary function testing (PFTs) showing a decrease in FVC% or DLCO%
predicted value of =10%.

3. Myositis - CPK > 2x upper limit of normal or MRI consistent with myositis

4. Childhood Myositis Assessment Score < 30

5. Arthritis

6. Digital tip ulcerations

5. Cardiology clearance to undergo stem cell transplantation (documented in subject's
medical chart)

6. Negative for human immunodeficiency virus (HIV), hepatitis B virus and hepatitis C
virus, all confirmed by PCR testing.

7. Negative pregnancy test for females. who have reached menarche.

87. All females of childbearing potential and sexually active males must agree to use an
FDA approved method of birth control for up to 24 months after BMT or for as long as they
are taking any medication that may harm a pregnancy, an unborn child or may cause a birth
defect.

Exclusion:

Individuals who meet any of these criteria are not eligible for this study.

1. FVC <35%, determined by pulmonary function tests for those able to complete spirometry
adequately (per investigator's determination)

2. O2 sat <92% at rest in room air

3. Estimated CrCl <40 mL/min,using Cockcroft-Gault formula based on actual body weight.

4. Active, untreated SSc renal crisis at the time of consent.

5. ALT > 4x upper limit of normal.

6. Active, uncontrolled infection that would be a contraindication to safe use of
high-dose immunosuppressive therapy or cyclophosphamide.

7. Hematologic abnormalities as defined by any of the following peripheral blood counts:

1. ANC < 1500 cell/µL.

2. Platelets < 100,000 cells/ µL.

3. Hemoglobin < 9.0 g/dL.

8. Malignancy within 2 years prior to enrollment, excluding adequately treated squamous
cell cancer, basal cell carcinoma or carcinoma in situ. Treatment should have been
completed with cure/remission status documented for at least 2 years.

9. Past or current medical problems or findings from medical history, physical
examination or laboratory testing that are not listed above, which, in the opinion of
the investigator, may pose additional risks from participation in the study, may
interfere with the participant's ability to comply with study requirements or that may
impact the quality or interpretation of the data obtained from the study.

Cohort 2 for Adults

Inclusion:

Individuals must meet all the following criteria to be eligible for this study.

1. Patient, parent, or legal guardian must have given written informed consent. For
patients = 16 years of age who are developmentally able, assent or affirmation will be
obtained.

2. Age 1618-705560, inclusive, at time of consent. Patients up to age 24, diagnosed with
SSc at age = 19, will be included in Cohort 1 and evaluated according to the Pediatric
and Young Adult criteria listed in sections 3.1.1 and 3.1.2.

3. Diagnosed with Systemic Sclerosis (SSc), according to the 2013 ACR/EULAR criteria (van
den Hoogen et al., 2013).

4. All patients must meet either the following skin or ILD criteria. Disease duration is
defined as time from first non-Raynaud symptom.

Skin Criteria: Diffuse SSc, defined by presence of proximal skin thickening and:

A. If disease duration is of <2 years, patients must have a calculated mortality risk
prediction score which places them in the intermediate or high- risk category (Domsic
et al., 2016). Refer to Appendix 5 for calculation criteria.

B. If disease duration is of >2 years, patients must have evidence of active cutaneous
disease based upon 1) a worsening Modified Rodnan Skin Score (MRSS) in the preceding
three months or 2) the presence of palpable tendon friction rubs.

ILD Criteria:

A. The presence of recognized fibrosis on imaging of <2 years AND either > 10% of lung
involvement by CT scan or FVC% pred <80% or B. Fibrosis on imaging of any duration
with a decline in FVC% pred of =10% over the preceding 12-18 months.

5. Negative for human immunodeficiency virus (HIV), hepatitis B virus and hepatitis C
virus, all confirmed by PCR testing.

6. Negative pregnancy test for females.

7. All females of childbearing potential and sexually active males must agree to use an
FDA approved method of birth control for up to 24 months after BMT or for as long as
they are taking any medication that may harm a pregnancy, an unborn child or may cause
a birth defect.

Exclusion Criteria Individuals who meet any of these criteria are not eligible for this
study.

1. Moderate to severe cardiac involvement defined by any of the following:

1. New York Heart Association classification of heart failure =3.

2. Left ventricular ejection fraction (LVEF) <50% as determined by cardiac MRI.

3. Significant pulmonary hypertension, for subjects = 18 years of age, defined as
mean PASP =30 mmHg determined by right heart catheterization, or for subjects =
17 years of age, defined as mean PASP >45 mmHg, determined by echocardiogram.

4. Atrial tachycardia, atrial fibrillation or atrial flutter of =1-minute duration,
determined by electrocardiogram (EKG) or, cardiac event monitor and/or implanted
loop recorder (if applicable), or on anti-arrhythmic therapy for the arrhythmias
listed above.

5. Ventricular tachycardia of =6 beats at rate of =100 beats per minute, determined
by EKG or, cardiac event moni


Age minimum: 8 Years
Age maximum: 60 Years
Gender: All

Health Condition(s) or Problem(s) studied

Pulmonary Hypertension

Diffuse Sclerosis Systemic

Systemic Sclerosis

Interstitial Lung Disease

Intervention(s)

Drug: Mesna

Drug: Thiotepa

Drug: Alemtuzumab

Drug: Cyclophosphamide

Drug: Intravenous immunoglobulin

Drug: Rituximab

Drug: GM-CSF

Radiation: Total Body Irradiation

Drug: Anti Thymocyte Globulin

Primary Outcome(s)

Death [Time Frame: Post Transplant through study completion, an average of 36 months]

The occurrence of cardiomyopathy [Time Frame: Post Transplant through study completion, an average of 36 months]

Treatment-related mortality (TRM) [Time Frame: Mobilization through study completion, an average of 36 months]

High Dose Immunoablative therapy-Safety [Time Frame: Up to 36 months post HSCT]

High Dose Immunoablative therapy-Treatment Effect [Time Frame: up to 36 months post HSCT (hematopoietic stem cell transplantation)]

Respiratory Failure [Time Frame: Post Transplant through study completion, an average of 36 months]

Renal Failure [Time Frame: Post Transplant through study completion, an average of 36 months]

Secondary Outcome(s)

Increase by =25% if the baseline mRSS > 20. [Time Frame: Disease response will be defined as subject improvement. This will be assessed for both skin and interstitial lung disease at 12 and 24 months post-HSCT.]

An increase of mRSS (modified Rodnan skin score ) by =5 points for skin score [Time Frame: Disease response will be defined as subject improvement. This will be assessed for both skin and interstitial lung disease at 12 and 24 months post-HSCT.]

Development of scleroderma renal crisis (hypertensive or non-hypertensive) [Time Frame: Post Transplant through study completion, an average of 36 months]

Worsening of > 10% of FVC (pulmonary function testing) [Time Frame: 1 year post transplant through study completion, an average of 36 months]

Worsening of cardiac involvement [Time Frame: Post Transplant through study completion, an average of 36 months]

Decrease in DLCO sustained for 3 months or longer on pulmonary function tests (PFT) [Time Frame: 1 year post transplant through study completion, an average of 36 months]

Secondary ID(s)

STUDY19050297

Source(s) of Monetary Support

Please refer to primary and secondary sponsors