Autologous Stem Cell Systemic Sclerosis Immune Suppression Trial (DIScl2011)
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ClinicalTrials.gov Identifier: NCT01445821 |
Recruitment Status :
Terminated
(Developed a better regimen: DIAD. Cast. 2018 NCT03593902)
First Posted : October 4, 2011
Results First Posted : July 23, 2020
Last Update Posted : July 23, 2020
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Condition or disease | Intervention/treatment | Phase |
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Scleroderma, Systemic | Biological: Peripheral Blood Stem Cells Drug: Cyclophosphamide Drug: Mesna Drug: rATG Drug: Methylprednisolone Drug: Filgrastim Drug: Fludarabine | Phase 3 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 44 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | Randomized Study of Different Non-myeloablative Conditioning Regimens With Hematopoietic Stem Cell Support in Patients With Scleroderma (Autologous Systemic Sclerosis Immune Suppression Trial - II ASSIST-IIb) |
Actual Study Start Date : | September 15, 2011 |
Actual Primary Completion Date : | January 5, 2017 |
Actual Study Completion Date : | October 10, 2019 |

Arm | Intervention/treatment |
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Active Comparator: Cyclophosphamide rATG/HSCT
The control arm will have the same conditioning regimen used in ASSIST study. The conditioning regimen will be 200 mg/kg of intravenous cyclophosphamide given in 4 equal fractions on days -5 through -2 with intravenous mesna. Rabbit antithymocyte globulin (rATG) (Thymoglobulin®) will be dosed at 0.5 mg/kg on day-5 and then 1.5 mg/kg from day-4 thru day -1. Methylprednisolone 1000 mg will be used infused intravenously before each dose of rATG. Peripheral blood stem cells (PBSC) will be infused intravenously on day 0. Filgrastim 5-10 mcg/kg will be started on day + 5 and continued until neutrophil engraftment.
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Biological: Peripheral Blood Stem Cells
Mobilized leukapheresis product Drug: Cyclophosphamide An alkylating agent which causes prevention of cell division by forming adducts with DNA
Other Names:
Drug: Mesna Medication used to decrease the risk of hemorrhagic cystitis prophylaxis
Other Name: Mesnex Drug: rATG A predominantly lymphocyte-specific immunosuppressive agent which contains antibodies specific to the antigens commonly found on the surface of T cells
Other Name: Thymoglobulin Drug: Methylprednisolone Steroid
Other Name: Solu-Medrol Drug: Filgrastim Granulocyte-colony stimulating factor (G-CSF); a glycoprotein that stimulates the bone marrow to produce granulocytes and stem cells and release them into the bloodstream
Other Names:
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Experimental: Cyclophosphamide rATG/Fludarabine/HSCT
The conditioning regimen will be 120 mg/kg of intravenous cyclophosphamide given in 2 equal fractions on days -3 and -2 with intravenous mesna. Rabbit antithymocyte globulin (rATG) (Thymoglobulin®) will be dosed at 0.5 mg/kg on day-5 and then 1.5 mg/kg from day-4 thru day -1. Fludarabine 30 mg/m2 will be given IV on days -5, -4, and -3. Methylprednisolone 1000 mg will be used infused intravenously before each dose of rATG. PBSC will be infused intravenously on day 0. Filgrastim 5-10 mcg/kg will be started on day + 5 and continued until neutrophil engraftment.
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Biological: Peripheral Blood Stem Cells
Mobilized leukapheresis product Drug: Cyclophosphamide An alkylating agent which causes prevention of cell division by forming adducts with DNA
Other Names:
Drug: Mesna Medication used to decrease the risk of hemorrhagic cystitis prophylaxis
Other Name: Mesnex Drug: rATG A predominantly lymphocyte-specific immunosuppressive agent which contains antibodies specific to the antigens commonly found on the surface of T cells
Other Name: Thymoglobulin Drug: Methylprednisolone Steroid
Other Name: Solu-Medrol Drug: Filgrastim Granulocyte-colony stimulating factor (G-CSF); a glycoprotein that stimulates the bone marrow to produce granulocytes and stem cells and release them into the bloodstream
Other Names:
Drug: Fludarabine Purine analog which inhibits DNA synthesis or repair
Other Name: Fludara |
- Number of Participants With Treatment Failure [ Time Frame: up to and post 12 months of treatment ]
Treatment failure will not occur until a minimum of 12 months after treatment at which time failure is defined as:
- Increase of skin score (if > 14 on enrollment) by > 25% above enrollment value and must be documented on 2 occasions at least 6 months apart
- Deterioration in percent predicted FVC by 10% below enrollment level, due to systemic sclerosis, and documented on 2 occasion at least 6 months apart
- Survival of Treatment [ Time Frame: up to 12 months post treatment ]Survival of Hematopoietic Stem Cell Transplant.

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Ages Eligible for Study: | 17 Years to 60 Years (Child, Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Age 17- 60 years old at the time of pretransplant evaluation
- An established diagnosis of scleroderma
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Diffuse cutaneous scleroderma with involvement proximal to the elbow or knee and a Rodnan score (see Appendix V) of > 14 AND
Scleroderma with 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.
- Pulmonary fibrosis or alveolitis on CT scan or chest X-ray (CXR) (ground glass appearance of alveolitis).
- Abnormal EKG [non-specific ST-segment and T-wave (ST-T) (pattern in electrocardiogram) wave abnormalities, low QRS (a pattern seen in an electrocardiogram that indicates the pulses in a heart beat and their duration) voltage, or ventricular hypertrophy], or pericardial effusion or pericardial enhancement 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 due to valvulae packing i.e. dilated and crowded circular folds may be present. GI involvement may also be confirmed by D-xylose malabsorption, patulous esophagus on HRCT, or esophageal manometry.
OR
- As published in New England Journal of Medicine (NEJM), 2006, 345:25 2655-2709. Limited or diffuse Systemic Sclerosis with (SSCL) with lung involvement defined as active alveolitis on Bronchoalveolar Lavage (BAL) or ground-glass opacity on CT, a DLCO < 80% predicted or decrease in lung function (DLCO/VA, DLCO, FVC) of 10% or more in last 12 months.
Exclusion Criteria:
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Significant end organ damage such as:
- Left Ventricular Function (LVEF) < 40% on echocardiogram.
- Untreated life-threatening arrhythmia.
- Active ischemic heart disease or heart failure.
- End-stage lung disease characterized by TLC<45% of predicted value, or DLCO hemoglobin corrected < 30% predicted .
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Pulmonary arterial hypertension defined on right heart catheterization as:
- a resting Mean Pulmonary Artery Pressure (mPAP) > 25 mmHg;
- a mPAP > 30 mmHg following a 500-1000 ml normal saline bolus;
- pulmonary vascular resistance (PVR) > 240 dynes*s/cm5 (> 3 Wood units) ; or
- a decrease in cardiac output with fluid challenge (500 - 1000 cc Normal Saline (NS) in 10 minutes) If fluid challenge cannot be done because right atrial (RA) pressure > 12mm Hg or pulmonary capillary wedge pressure (PCWP) > 15 m Hg at rest or must be stopped due to safety concerns, patient is excluded as candidate.
- Serum creatinine > 1.4 mg/dl.
- Liver cirrhosis, transaminases > 3x of normal limits or bilirubin > 2.0 unless due to Gilbert's disease.
- Pericardial effusion > 1 cm on cardiac MRI unless successful pericardiocentesis has been performed
- Occult or clinical constrictive pericarditis
- On echocardiogram tricuspid annular peak systolic excursion (TAPSE) ≤ 1.8 cm or, grade II or worse Right Ventricular (RV) or Left Ventricular (LV) diastolic dysfunction
- On cardiac MRI, a diastolic septal bounce or diastolic septal flattering (D-sign), or diffuse myocardial gadolinium enhancement, or diffuse hypokinesis (patchy late gadolinium myocardial enhancement are not exclusion criteria)
- Ventricular tachycardia (sustained or non-sustained, multifocal or unifocal) on EKG or 24 hour Holter
- HIV positive.
- 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, 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.
- Inability to give informed consent.
- Major hematological abnormalities such as platelet count < 100,000/ul or absolute neutrophil count (ANC) < 1000/ul.
- Hepatitis B or C positive

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01445821
United States, Illinois | |
Northwestern University | |
Chicago, Illinois, United States, 60611 |
Principal Investigator: | Richard Burt, MD | Northwestern University |
Responsible Party: | Richard Burt, MD, Chief, Division of Medicine-Immunotherapy and Autoimmune Diseases; Professor in Medicine-Immunotherapy and Autoimmune Diseases, Northwestern University |
ClinicalTrials.gov Identifier: | NCT01445821 |
Other Study ID Numbers: |
ASSIST IIb |
First Posted: | October 4, 2011 Key Record Dates |
Results First Posted: | July 23, 2020 |
Last Update Posted: | July 23, 2020 |
Last Verified: | June 2020 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
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 |
Autologous Stem Cell Transplantation |
Scleroderma, Systemic Scleroderma, Diffuse Connective Tissue Diseases Skin Diseases Methylprednisolone Methylprednisolone Hemisuccinate Cyclophosphamide Fludarabine Thymoglobulin Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antirheumatic Agents Antineoplastic Agents, Alkylating Alkylating Agents |
Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Myeloablative Agonists Anti-Inflammatory Agents Antiemetics Autonomic Agents Peripheral Nervous System Agents Gastrointestinal Agents Glucocorticoids Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Neuroprotective Agents Protective Agents Antineoplastic Agents, Hormonal |