Autologous Stem Cell Transplantation in Patients With Systemic Sclerosis

NCT03630211 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: STUDY19050297
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this study is to determine whether a regimen of high-dose immunoablative therapy will demonstrate safety that is consistent or improved with other published regimens in SSc patients, while maintaining a treatment effect.

Conditions

Systemic Sclerosis; Diffuse Sclerosis Systemic; Interstitial Lung Disease; Pulmonary Hypertension

Keywords

Stem Cell Transplantation; Systemic Sclerosis; Scleroderma; Interstitial Lung Disease; ILD (Interstitial Lung Disease); Pulmonary Hypertension; BMT ( bone marrow transplantation); Autologous

Outcome Measures

Primary Outcomes (7)

• High Dose Immunoablative therapy-Safety

  Safety will be determined by monitoring for death of any cause, regimen-related toxicities, and severe or life-threatening infections.

  Up to 36 months post HSCT

• Death

  How many, if any, patients die

  Post Transplant through study completion, an average of 36 months

• Respiratory Failure

  defined by one of the following 3 criteria without explanation for causation other than disease progression: 1. decline in DLCO of ≥30% or FVC≥20% as measured by actual difference in percent predicted units; 2. Resting arterial p02 \< 60 mmHg or pCO2 \> 50 mmHg supplemental oxygen;3. Resting pulse oximetry of 88% or lower measured by forehead probe.

  Post Transplant through study completion, an average of 36 months

• Renal Failure

  Defined by chronic dialysis for \>6 months or renal transplantation

  Post Transplant through study completion, an average of 36 months

• The occurrence of cardiomyopathy

  confirmed by clinical congestive heart failure (New York Heart Association) or LVEF (left ventricular ejection fraction) \<30% on echocardiogram

  Post Transplant through study completion, an average of 36 months

• Treatment-related mortality (TRM)

  defined as death occurring at any time after stem cell mobilization and definitely or probably resulting from treatment given in the study. TRM will be determined yearly with a focus on the first 2 years.

  Mobilization through study completion, an average of 36 months

• High Dose Immunoablative therapy-Treatment Effect

  Treatment effect will be determined by assessing event-free survival in comparison to a SSc observational cohort control group treated with standard of care medication (mycophenolate mofetil) at 12 and 36 months post hematopoietic stem cell transplant (HSCT).

  up to 36 months post HSCT (hematopoietic stem cell transplantation)

Secondary Outcomes (6)

• An increase of mRSS (modified Rodnan skin score ) by ≥5 points for skin score

  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.

• Increase by ≥25% if the baseline mRSS > 20.

  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.

• Worsening of > 10% of FVC (pulmonary function testing)

  1 year post transplant through study completion, an average of 36 months

• Decrease in DLCO sustained for 3 months or longer on pulmonary function tests (PFT)

  1 year post transplant through study completion, an average of 36 months

• Worsening of cardiac involvement

  Post Transplant through study completion, an average of 36 months

Study Arms (1)

Autologous Stem Cell Transplantation

EXPERIMENTAL

CD34-selected autologous stem cell being performed on CliniMACS depletion device. Conditioning regimen will not start sooner than 3 weeks, and ideally no more than 90 days, after cyclophosphamide dose in the mobilization regimen.

Drug: Cyclophosphamide; Drug: Mesna; Drug: Rituximab; Drug: Alemtuzumab; Drug: Thiotepa; Drug: GM-CSF; Drug: Intravenous immunoglobulin; Radiation: Total Body Irradiation; Drug: Anti Thymocyte Globulin

Interventions

Cyclophosphamide DRUG

Stem Cell Mobilization

Autologous Stem Cell Transplantation

Mesna DRUG

Stem Cell Mobilization

Autologous Stem Cell Transplantation

Rituximab DRUG

Transplantation Conditioning

Also known as: Rituxan

Autologous Stem Cell Transplantation

Alemtuzumab DRUG

Transplantation Conditioning

Also known as: Campath-1H

Autologous Stem Cell Transplantation

Thiotepa DRUG

Transplantation Conditioning

Autologous Stem Cell Transplantation

GM-CSF DRUG

Transplantation Conditioning

Also known as: Neupogen, Filgrastim

Autologous Stem Cell Transplantation

Intravenous immunoglobulin DRUG

Transplantation Conditioning

Autologous Stem Cell Transplantation

Total Body Irradiation RADIATION

Transplantation Conditioning

Autologous Stem Cell Transplantation

Anti Thymocyte Globulin DRUG

Transplantation Conditioning

Also known as: Thymoglobulin

Autologous Stem Cell Transplantation

Eligibility Criteria

• Age: 8 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Individuals must meet all the following criteria to be eligible for this study.
• 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.
• Age 8-24, inclusive, at time of consent.
• Diagnosed with Systemic Sclerosis (SSc) at the age of ≤19.
• 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:
• Progression of skin thickening over the past 6 months or Modified Rodnan skin score (mRSS) ≥ 20
• 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%.
• Myositis - CPK \> 2x upper limit of normal or MRI consistent with myositis
• Childhood Myositis Assessment Score \< 30
• Arthritis
• Digital tip ulcerations
• Cardiology clearance to undergo stem cell transplantation (documented in subject's medical chart)
• Negative for human immunodeficiency virus (HIV), hepatitis B virus and hepatitis C virus, all confirmed by PCR testing.

You may not qualify if:

• Individuals who meet any of these criteria are not eligible for this study.
• FVC \<35%, determined by pulmonary function tests for those able to complete spirometry adequately (per investigator's determination)
• O2 sat \<92% at rest in room air
• Estimated CrCl \<40 mL/min,using Cockcroft-Gault formula based on actual body weight.
• Active, untreated SSc renal crisis at the time of consent.
• ALT \> 4x upper limit of normal.
• Active, uncontrolled infection that would be a contraindication to safe use of high-dose immunosuppressive therapy or cyclophosphamide.
• Hematologic abnormalities as defined by any of the following peripheral blood counts:
• ANC \< 1500 cell/µL.
• Platelets \< 100,000 cells/ µL.
• Hemoglobin \< 9.0 g/dL.
• 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.
• 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
• Individuals must meet all the following criteria to be eligible for this study.

Sponsors & Collaborators

• Paul Szabolcs: lead

Study Sites (3)

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15213, United States

RECRUITING

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15261, United States

RECRUITING

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15261, United States

RECRUITING

MeSH Terms

Conditions

Scleroderma, Systemic; Scleroderma, Diffuse; Lung Diseases, Interstitial; Hypertension, Pulmonary

Interventions

Cyclophosphamide; Mesna; Rituximab; Alemtuzumab; Thiotepa; Granulocyte-Macrophage Colony-Stimulating Factor; Filgrastim; Immunoglobulins, Intravenous; Whole-Body Irradiation; Antilymphocyte Serum; thymoglobulin

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases; Lung Diseases; Respiratory Tract Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Sulfhydryl Compounds; Sulfur Compounds; Sulfonic Acids; Sulfur Acids; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Antibodies, Monoclonal, Humanized; Triethylenephosphoramide; Aziridines; Azirines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Biological Factors; Granulocyte Colony-Stimulating Factor; Immunoglobulin G; Immunoglobulin Isotypes; Radiotherapy; Therapeutics; Investigative Techniques; Immune Sera; Biological Products; Complex Mixtures

Study Officials

• Paul Szabolcs, MD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Paul Szabolcs, MD

CONTACT

412-692-6225; paul.szabolcs@chp.edu

Shawna McIntyre, RN

CONTACT

412-692-5552; mcintyresm@upmc.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chief, Division of Blood and Marrow Transplantation and Cellular Therapy

Study Record Dates

• First Submitted: August 7, 2018
• First Posted: August 14, 2018
• Study Start: July 31, 2018
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2026
• Last Updated: October 15, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)