Cardiac Safe Transplants for Systemic Sclerosis (CAST)

August 10, 2020 updated by: Richard Burt, MD, Northwestern University

Autologous Hematopoietic Stem Cell Transplant for Patients With Systemic Sclerosis and Cardiac Dysfunction

This study is designed to treat systemic sclerosis (scleroderma) patients with an autologous stem cell transplant using a regimen of immune suppressant drugs and chemotherapy that is less toxic to your heart.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

The autologous hematopoietic stem cell transplant used in this research study is an investigational procedure that uses cyclophosphamide and fludarabine (chemotherapy), rabbit anti-thymocyte globulin (rATG) (a protein that kills the immune cells that are thought to be causing your disease), and rituximab (a biologic drug that targets B cells of your immune system). After use of these treatments, the patient will receive their own previously collected blood stem cells (autologous stem cell transplant). The ability of these experimental treatments to stop relapses and progression (worsening) of your systemic sclerosis will be assessed.

Study Type

Interventional

Enrollment (Actual)

9

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern University
      • Chicago, Illinois, United States, 60611
        • Northwestern University, Feinberg School of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Age 18 - 65 years old at the time of pre-transplant evaluation
  2. An established diagnosis of systemic sclerosis
  3. Diffuse cutaneous systemic sclerosis with involvement proximal to the elbow or knee and a modified Rodnan Skin Score of ≥ 14 (see Appendix A)

AND

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 (ground glass appearance of alveolitis).
  3. Abnormal EKG (non-specific ST-T wave abnormalities, low QRS voltage, or ventricular hypertrophy), or pericardial effusion or pericardial enhancement without constriction 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 may be present (e.g. dilated and crowded circular folds). GI involvement may also be confirmed by D-xylose malabsorption, patulous esophagus on high-resolution computed tomography (HRCT), or esophageal manometry.

OR

Limited cutaneous systemic sclerosis (SSc) (modified Rodnan Skin Score <14) with lung involvement defined as active alveolitis on bronchoalveolar lavage (BAL), ground-glass opacity on CT scan, a DLCO < 80% predicted, or decrease in lung function (DLCO/VA, DLCO, FVC) of 10% or more in last 12 months.

Other Inclusion Criteria for "CAST" Conditioning Regimen (presence of any of the following):

  1. Septal flattening or D-sign on MRI (without deep breathing)
  2. PASP >40 mm Hg or >45 mm Hg with fluid challenge*
  3. mPAP >25 mm Hg or >30 mm Hg with fluid challenge*

  4. Non-ischemia diffuse ventricular hypokinesis or non-ischemia wall hypokinesis

    • Fluid challenge is 1000 ml normal saline over 10 minutes. Fluid challenge will not be done if right atrial pressure is >13 mm Hg at rest or pulmonary capillary wedge pressure is >20 mm Hg at rest.

Exclusion Criteria:

  1. Active ischemic heart disease or untreated coronary artery disease
  2. Untreated life-threatening cardiac arrhythmia on EKG or 24-hour holter
  3. Pericardial effusion > 1 cm on cardiac MRI unless successful pericardiocentesis has been performed
  4. LVEF <35%
  5. End-stage lung disease characterized by TLC<45% of predicted value, or DLCO hemoglobin corrected < 30 % predicted.
  6. Creatinine clearance <40 by 24-hour urine
  7. History of breast implants that have not been removed (unless they cannot be surgically removed due to risks of surgery)
  8. Liver cirrhosis, transaminases >2x of normal limits, or bilirubin > 2.0 unless due to Gilbert's disease
  9. 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
  10. Prior history of malignancy
  11. Positive pregnancy test, inability or unable to pursue effective means of birth control, or failure to willingly accept or comprehend irreversible sterility as a side effect of therapy
  12. Psychiatric illness or mental deficiency making compliance with treatment or informed consent impossible
  13. Major hematological abnormalities such as platelet count < 100,000/ul or absolute neutrophil count (ANC) < 1000/ul
  14. HIV positive
  15. Hepatitis B or C positive
  16. PASP >50 mmHg without fluid challenge
  17. mPAP >34 mmHg without fluid challenge
  18. Coronary artery disease not reversed by cardiology and interventional radiology

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Hematopoietic Stem Cell Transplantation
Hematopoietic Stem Cell Therapy will be performed as follows: Autologous stem cells will be infused after conditioning with rituximab, fludarabine, cyclophosphamide, Mesna, rATG (rabbit), and methylprednisolone. Granulocyte-colony stimulating factor (G-CSF) and intravenous immunoglobulin (IVIg) will be administered post-transplant.
Drug: Cyclophosphamide
A medication used as chemotherapy and to suppress the immune system
Other Names:
  • Cytoxan
Drug: G-CSF
A glycoprotein that stimulates the bone marrow to produce granulocytes and stem cells and release them into the bloodstream
Other Names:
  • Filgrastim
  • Neupogen
  • Zarxio
  • Granix
Drug: rATG
A rabbit polyclonal antibody to lymphocytes
Other Names:
  • Thymoglobulin
  • Anti-Thymocyte Globulin (Rabbit)
Drug: Mesna
A medication used in those taking cyclophosphamide or ifosfamide to decrease the risk of bleeding from the bladder
Other Names:
  • Mesnex
Drug: Rituximab
Monoclonal antibody therapy used to treat certain autoimmune diseases and types of cancer
Other Names:
  • Rituxan
Drug: Methylprednisolone
A corticosteroid medication used to suppress the immune system and decrease inflammation
Other Names:
  • Depo-Medrol
  • Solu-Medrol
Biological: IVIg
Pooled immunoglobulin (IgG) from thousands of plasma donors that has immunomodulatory and anti-inflammatory effects
Other Names:
  • Gammagard
  • Privigen
  • Octagam
  • Bivagam
  • Carimune NF
Biological: Autologous Stem Cells
Infusion of patient's own stem cells
Drug: Fludarabine
A chemotherapy medication commonly used in the treatment of leukemia and lymphoma
Other Names:
  • Fludara

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Skin Score by mRSS
Time Frame: Pre Treatment and Post Treatment
Defined by at least a 25% improvement (decline) in skin score by modified Rodnan skin score (mRSS) if skin score is greater than 14 on enrollment. If skin score is less than 14 on enrollment, improvement is defined by at least a 5% improvement on mRSS. The modified Rodnan skin score (MRSS) is a measure for skin disease in scleroderma and is calculated by summation of skin thickness in 17 different body sites. The scale ranges from at total score of normal skin thickness (0) to severe thickness (51).
Pre Treatment and Post Treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Survival of Treatment
Time Frame: During Treatment and Post Treatment up to 1 year
Survival of Hematopoietic Stem Cell Transplant during treatment and post treatment up to 1 year.
During Treatment and Post Treatment up to 1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Northwestern University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 17, 2018

Primary Completion (Actual)

October 3, 2019

Study Completion (Actual)

October 9, 2019

Study Registration Dates

First Submitted

June 28, 2018

First Submitted That Met QC Criteria

July 10, 2018

First Posted (Actual)

July 20, 2018

Study Record Updates

Last Update Posted (Actual)

August 12, 2020

Last Update Submitted That Met QC Criteria

August 10, 2020

Last Verified

June 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DIAD.CAST.2018

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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