Cardiac Safe Transplants for Systemic Sclerosis

NCT ID: NCT03593902

Last Updated: 2020-08-12

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

TERMINATED

Clinical Phase

PHASE2/PHASE3

Total Enrollment

9 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-05-17

Study Completion Date

2019-10-09

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Systemic Sclerosis Scleroderma

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

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.

Group Type EXPERIMENTAL

Rituximab

Intervention Type DRUG

Monoclonal antibody therapy used to treat certain autoimmune diseases and types of cancer

Fludarabine

Intervention Type DRUG

A chemotherapy medication commonly used in the treatment of leukemia and lymphoma

Cyclophosphamide

Intervention Type DRUG

A medication used as chemotherapy and to suppress the immune system

Mesna

Intervention Type DRUG

A medication used in those taking cyclophosphamide or ifosfamide to decrease the risk of bleeding from the bladder

rATG

Intervention Type DRUG

A rabbit polyclonal antibody to lymphocytes

Methylprednisolone

Intervention Type DRUG

A corticosteroid medication used to suppress the immune system and decrease inflammation

G-CSF

Intervention Type DRUG

A glycoprotein that stimulates the bone marrow to produce granulocytes and stem cells and release them into the bloodstream

IVIg

Intervention Type BIOLOGICAL

Pooled immunoglobulin (IgG) from thousands of plasma donors that has immunomodulatory and anti-inflammatory effects

Autologous Stem Cells

Intervention Type BIOLOGICAL

Infusion of patient's own stem cells

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Rituximab

Monoclonal antibody therapy used to treat certain autoimmune diseases and types of cancer

Intervention Type DRUG

Fludarabine

A chemotherapy medication commonly used in the treatment of leukemia and lymphoma

Intervention Type DRUG

Cyclophosphamide

A medication used as chemotherapy and to suppress the immune system

Intervention Type DRUG

Mesna

A medication used in those taking cyclophosphamide or ifosfamide to decrease the risk of bleeding from the bladder

Intervention Type DRUG

rATG

A rabbit polyclonal antibody to lymphocytes

Intervention Type DRUG

Methylprednisolone

A corticosteroid medication used to suppress the immune system and decrease inflammation

Intervention Type DRUG

G-CSF

A glycoprotein that stimulates the bone marrow to produce granulocytes and stem cells and release them into the bloodstream

Intervention Type DRUG

IVIg

Pooled immunoglobulin (IgG) from thousands of plasma donors that has immunomodulatory and anti-inflammatory effects

Intervention Type BIOLOGICAL

Autologous Stem Cells

Infusion of patient's own stem cells

Intervention Type BIOLOGICAL

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Rituxan Fludara Cytoxan Mesnex Thymoglobulin Anti-Thymocyte Globulin (Rabbit) Solu-Medrol Depo-Medrol Neupogen Filgrastim Granix Zarxio Bivagam Carimune NF Gammagard Privigen Octagam

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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.


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
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Northwestern University

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Richard Burt, MD

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Richard Burt, MD

Role: PRINCIPAL_INVESTIGATOR

Northwestern University

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Northwestern University, Feinberg School of Medicine

Chicago, Illinois, United States

Site Status

Northwestern University

Chicago, Illinois, United States

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States

References

Explore related publications, articles, or registry entries linked to this study.

Burt RK, Han X, Quigley K, Arnautovic I, Shah SJ, Lee DC, Freed BH, Jovanovic B, Helenowski IB. Cardiac safe hematopoietic stem cell transplantation for systemic sclerosis with poor cardiac function: a pilot safety study that decreases neutropenic interval to 5 days. Bone Marrow Transplant. 2021 Jan;56(1):50-59. doi: 10.1038/s41409-020-0978-2. Epub 2020 Jul 1.

Reference Type DERIVED
PMID: 32612255 (View on PubMed)

Provided Documents

Download supplemental materials such as informed consent forms, study protocols, or participant manuals.

Document Type: Statistical Analysis Plan

View Document

Document Type: Study Protocol

View Document

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

DIAD.CAST.2018

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

JAK/STAT Inhibition in CNS Kohlmeier-Degos Disease
NCT05998395 COMPLETED PHASE1/PHASE2
Antibody Production in Immune Disorders
NCT00023504 TERMINATED PHASE4
Rituximab for Pulmonary Sarcoidosis
NCT00855205 COMPLETED PHASE2
CNS Sarcoidosis and Acthar Gel
NCT02298491 COMPLETED PHASE4