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Systemic SclerosisPhase 2/3CASTNCT03593902

Cardiac Safe Transplants for Systemic Sclerosis

A Phase 2/3 study testing Rituximab, Fludarabine and Cyclophosphamide in people with Systemic Sclerosis and Scleroderma, run by Northwestern University at 2 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Systemic Sclerosis, Scleroderma
What is being tested?
Rituximab, Fludarabine and Cyclophosphamide
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
9 participants
Where
2 sitesUnited States
Study dates
17 May 2018to 9 Oct 2019
Phase
Phase 2/3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age 18 - 65 years old at the time of pre-transplant evaluation
  • An established diagnosis of systemic sclerosis
  • 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:
  • DLCO < 80% of predicted or decrease in lung function (DLCO, DLCO/VA or FVC) of 10% or more over 12 months.
Show all 17Show fewer
  • Pulmonary fibrosis or alveolitis on CT scan or chest x-ray (ground glass appearance of alveolitis).
  • Abnormal EKG (non-specific ST-T wave abnormalities, low QRS voltage, or ventricular hypertrophy), or pericardial effusion or pericardial enhancement without constriction on MRI
  • 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):
  • Septal flattening or D-sign on MRI (without deep breathing)
  • PASP >40 mm Hg or >45 mm Hg with fluid challenge*
  • mPAP >25 mm Hg or >30 mm Hg with fluid challenge*
  • 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.

Who cannot join

  • Active ischemic heart disease or untreated coronary artery disease
  • Untreated life-threatening cardiac arrhythmia on EKG or 24-hour holter
  • Pericardial effusion > 1 cm on cardiac MRI unless successful pericardiocentesis has been performed
  • LVEF <35%
  • End-stage lung disease characterized by TLC<45% of predicted value, or DLCO hemoglobin corrected < 30 % predicted.
  • Creatinine clearance <40 by 24-hour urine
Show all 18Show fewer
  • History of breast implants that have not been removed (unless they cannot be surgically removed due to risks of surgery)
  • Liver cirrhosis, transaminases >2x of normal limits, or bilirubin > 2.0 unless due to Gilbert's disease
  • 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
  • Prior history of malignancy
  • 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
  • Psychiatric illness or mental deficiency making compliance with treatment or informed consent impossible
  • Major hematological abnormalities such as platelet count < 100,000/ul or absolute neutrophil count (ANC) < 1000/ul
  • HIV positive
  • Hepatitis B or C positive
  • PASP >50 mmHg without fluid challenge
  • mPAP >34 mmHg without fluid challenge
  • Coronary artery disease not reversed by cardiology and interventional radiology

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Northwestern University, Feinberg School of Medicine

    Chicago, Illinois, 60611

  • Northwestern University

    Chicago, Illinois, 60611

Other trials in United States

About this study

Official title: 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.

Read the 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.

Being tested
Rituximab, Fludarabine, Cyclophosphamide, Mesna, rATG
Keywords
Autologous Stem Cell Transplantation, Hematopoietic Stem Cell Transplant
Medical subject headings
Scleroderma, Systemic, Scleroderma, Diffuse

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RituximabDrug

    Also called Rituxan

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

  • FludarabineDrug

    Also called Fludara

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

  • CyclophosphamideDrug

    Also called Cytoxan

    A medication used as chemotherapy and to suppress the immune system

  • MesnaDrug

    Also called Mesnex

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

  • rATGDrug

    Also called Thymoglobulin, Anti-Thymocyte Globulin (Rabbit)

    A rabbit polyclonal antibody to lymphocytes

  • MethylprednisoloneDrug

    Also called Solu-Medrol, Depo-Medrol

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

  • G-CSFDrug

    Also called Neupogen, Filgrastim, Granix, Zarxio

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

  • IVIgBiological

    Also called Bivagam, Carimune NF, Gammagard, Privigen

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

  • Autologous Stem CellsBiological

    Infusion of patient's own stem cells

Study groups in NCT03593902
Study groupRoleWhat they receive
Hematopoietic Stem Cell TransplantationExperimentalHematopoietic 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.
Receives: Drug: Rituximab; Drug: Fludarabine; Drug: Cyclophosphamide; Drug: Mesna; Drug: rATG; Drug: Methylprednisolone; Drug: G-CSF; Biological: IVIg; Biological: Autologous Stem Cells

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in Skin Score by mRSS

    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).

    Measured: Pre Treatment and Post Treatment

Secondary outcomes (1)

  1. Survival of Treatment

    Survival of Hematopoietic Stem Cell Transplant during treatment and post treatment up to 1 year.

    Measured: During Treatment and Post Treatment up to 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Jul 2018
  2. Study start17 May 2018
  3. Primary completion3 Oct 2019
  4. Study completion9 Oct 2019

Why it stopped: PI Sabbatical

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
9 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03593902
Sponsor's protocol ID
DIAD.CAST.2018
Acronym
CAST
Status last verified
Jun 2020
First submitted
28 Jun 2018
Last updated
12 Aug 2020
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 32612255

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Rituximab, Fludarabine and Cyclophosphamide in people with Systemic Sclerosis and Scleroderma, run by Northwestern University at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 12 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 12 Aug 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Skin Score by mRSS (time frame: Pre Treatment and Post Treatment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03593902, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Aug 2020.

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