DIScl2011: Autologous Stem Cell Systemic Sclerosis Immune Suppression Trial

• Sponsor: Northwestern University (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01445821
• Collaborator: (none)
• Enrollment: 44
• Location: 1
• Arms: 2
• Actual Duration (Months): 96.8
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

ASSIST I was the first randomized trial in patients with scleroderma to not just slow disease progression but rather actually reverse it. It is the first treatment to have ever demonstrated reversal of lung disease in scleroderma with improvement in FVC, total lung capacity (TLC), high-resolution computed tomography (HRCT), and QOL. We now, therefore, purpose to compare the ASSIST I conditioning regimen of cyclophosphamide and rATG to a less intense regimen of rATG/cyclophosphamide/Fludarabine. In the new regimen the cyclophosphamide dose is decreased to 120mg/kg (60mg/kg/day x 2) compared to 200mg/kg (50mg/kg/day) in the standard regimen. The lower dose of cyclophosphamide will be less cardiotoxic. This study will determine if the less cardiotoxic regimen will be safer than the standard regimen and as effective as the standard regimen.

Condition or Disease	Intervention/Treatment	Phase
Scleroderma, Systemic	Biological: Peripheral Blood Stem Cells; Drug: Cyclophosphamide; Drug: Mesna; Drug: rATG; Drug: Methylprednisolone; Drug: Filgrastim; Drug: Fludarabine	Phase 3

Detailed Description

Mobilization. For patients in both arms undergoing hematopoietic stem cell transplantation (HSCT), peripheral blood stem cells (PBSC) will be mobilized with cyclophosphamide (2 g/m2) followed by 5-10 mcg/kg subcutaneous filgrastrim daily from day 5 until completion of apheresis. Mobilized hematopoietic stem cells (HSC) will be collected by apheresis on day 10 and cryopreserved without selection or manipulation. There will be an interval of at least 17 days between mobilization of PBSC and start of conditioning regimen.

Study Design

• Study Type: Interventional
• 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: Sep 15, 2011
• Actual Primary Completion Date: Jan 5, 2017
• Actual Study Completion Date: Oct 10, 2019

Arms and Interventions

Arm	Intervention/Treatment
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.	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: Cytoxan Neosar Endoxan ; Drug: Mesna; Medication used to decrease the risk of hemorrhagic cystitis prophylaxis; Other Names: 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 Names: Thymoglobulin ; Drug: Methylprednisolone; Steroid; Other Names: 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: Neupogen G-CSF Granix Zarxio
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.	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: Cytoxan Neosar Endoxan ; Drug: Mesna; Medication used to decrease the risk of hemorrhagic cystitis prophylaxis; Other Names: 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 Names: Thymoglobulin ; Drug: Methylprednisolone; Steroid; Other Names: 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: Neupogen G-CSF Granix Zarxio ; Drug: Fludarabine; Purine analog which inhibits DNA synthesis or repair; Other Names: Fludara

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Treatment Failure [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

Secondary Outcome Measures

1. Survival of Treatment [up to 12 months post treatment]

   Survival of Hematopoietic Stem Cell Transplant.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 17 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Age 17- 60 years old at the time of pretransplant evaluation

2. An established diagnosis of scleroderma

3. 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:

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 (CXR) (ground glass appearance of alveolitis).

3. 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

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 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

1. 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:

1. Significant end organ damage such as:

2. Left Ventricular Function (LVEF) < 40% on echocardiogram.

3. Untreated life-threatening arrhythmia.

4. Active ischemic heart disease or heart failure.

5. End-stage lung disease characterized by TLC<45% of predicted value, or DLCO hemoglobin corrected < 30% predicted .

6. Pulmonary arterial hypertension defined on right heart catheterization as:

7. a resting Mean Pulmonary Artery Pressure (mPAP) > 25 mmHg;

8. a mPAP > 30 mmHg following a 500-1000 ml normal saline bolus;

9. pulmonary vascular resistance (PVR) > 240 dynes*s/cm5 (> 3 Wood units) ; or

10. 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.

1. Serum creatinine > 1.4 mg/dl.

2. Liver cirrhosis, transaminases > 3x of normal limits or bilirubin > 2.0 unless due to Gilbert's disease.

3. Pericardial effusion > 1 cm on cardiac MRI unless successful pericardiocentesis has been performed

4. Occult or clinical constrictive pericarditis

5. 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

6. 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)

7. Ventricular tachycardia (sustained or non-sustained, multifocal or unifocal) on EKG or 24 hour Holter

8. HIV positive.

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, 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. Inability to give informed consent.

14. Major hematological abnormalities such as platelet count < 100,000/ul or absolute neutrophil count (ANC) < 1000/ul.

15. Hepatitis B or C positive

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Northwestern University	Chicago	Illinois	United States	60611

Sponsors and Collaborators

• Northwestern University

Investigators

• Principal Investigator: Richard Burt, MD, Northwestern University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• 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: Oct 4, 2011
• Last Update Posted: Jul 23, 2020
• Last Verified: Jun 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• 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
• Keywords provided by Richard Burt, MD, Chief, Division of Medicine-Immunotherapy and Autoimmune Diseases; Professor in Medicine-Immunotherapy and Autoimmune Diseases, Northwestern University: Autologous Stem Cell Transplantation
• Additional relevant MeSH terms: Scleroderma, Systemic; Scleroderma, Diffuse; Methylprednisolone; Methylprednisolone Hemisuccinate; Cyclophosphamide; Fludarabine; Thymoglobulin

Study Results

Participant Flow

Arm/Group Title	Cyclophosphamide rATG/HSCT	Cyclophosphamide rATG/Fludarabine/HSCT
Arm/Group Description	Conditioning regimen will be 200 mg/kg of intravenous cyclophosphamide given in 4 equal fractions on days -5 through -2 with IV 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. Peripheral Blood Stem Cells: Mobilized leukapheresis product Cyclophosphamide: Alkylating agent Mesna: Used to decrease the risk of hemorrhagic cystitis rATG: Immunosuppressive agent which contains antibodies specific to the antigens Methylprednisolone: Steroid Filgrastim: Granulocyte-colony stimulating factor (G-CSF); a glycoprotein that stimulates the bone marrow to produce granulocytes and stem cells	Conditioning regimen will be 120 mg/kg of IV cyclophosphamide given in 2 equal fractions on days -3 and -2 with IV mesna. Rabbit antithymocyte globulin (rATG) (Thymoglobulin®) will be dosed at 0.5 mg/kg on day-5 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 IV before each dose of rATG. PBSC will be infused IV on day 0. Filgrastim 5-10 mcg/kg will be started on day + 5 and cont. until neutrophil engraftment. Peripheral Blood Stem Cells: Mobilized leukapheresis product Cyclophosphamide: Alkylating agent Mesna: Used to decrease the risk of hemorrhagic cystitis rATG: Immunosuppressive agent which contains antibodies specific to the antigens Methylprednisolone: Steroid Filgrastim: Granulocyte-colony stimulating factor (G-CSF);glycoprotein that stimulates the bone marrow to produce granulocytes/stem cells Fludarabine: Purine analog which inhibits DNA synthesis/repair
Period Title: Overall Study
STARTED	22	22
COMPLETED	22	22
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Cyclophosphamide rATG/HSCT	Cyclophosphamide rATG/Fludarabine/HSCT	Total
Arm/Group Description	Conditioning regimen: 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. Peripheral Blood Stem Cells: Mobilized leukapheresis product Cyclophosphamide: An alkylating agent Mesna: Used to decrease the risk of hemorrhagic cystitis rATG: Immunosuppressive agent which contains antibodies specific to the antigens Methylprednisolone: Steroid Filgrastim: Granulocyte-colony stimulating factor (G-CSF); a glycoprotein that stimulates the bone marrow to produce granulocytes and stem cells	Conditioning regimen: 120 mg/kg of IV cyclophosphamide given in 2 equal fractions on days -3 and -2 with IV 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 IV before each dose of rATG. PBSC will be infused IV on day 0. Filgrastim 5-10 mcg/kg will be started on day + 5 and cont. until neutrophil engraftment. Peripheral Blood Stem Cells: Mobilized leukapheresis product Cyclophosphamide: Alkylating agent Mesna: Used to decrease the risk of hemorrhagic cystitis rATG: Immunosuppressive agent which contains antibodies specific to the antigens Methylprednisolone: Steroid Filgrastim: Granulocyte-colony stimulating factor (G-CSF);glycoprotein that stimulates the bone marrow to produce granulocytes and stem cells Fludarabine: Purine analog which inhibits DNA synthesis/repair	Total of all reporting groups
Overall Participants	22	22	44
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	22 100%	22 100%	44 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	42.8	45.6	44.2
Sex: Female, Male (Count of Participants)
Female	16 72.7%	18 81.8%	34 77.3%
Male	6 27.3%	4 18.2%	10 22.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	2 9.1%	2 4.5%
White	20 90.9%	17 77.3%	37 84.1%
More than one race	2 9.1%	3 13.6%	5 11.4%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	22 100%	22 100%	44 100%
Skin Score Prior to Treatment (units on a scale) [Mean (Full Range) ]
Mean (Full Range) [units on a scale]	26.1	22.8	24.14

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Treatment Failure
Description	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
Time Frame	up to and post 12 months of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cyclophosphamide rATG/HSCT	Cyclophosphamide rATG/Fludarabine/HSCT
Arm/Group Description	Conditioning regimen will be 200 mg/kg of intravenous cyclophosphamide given in 4 equal fractions on days -5 through -2 with IV 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. Peripheral Blood Stem Cells: Mobilized leukapheresis product Cyclophosphamide: Alkylating agent Mesna: Used to decrease the risk of hemorrhagic cystitis rATG: Immunosuppressive agent which contains antibodies specific to the antigens Methylprednisolone: Steroid Filgrastim: Granulocyte-colony stimulating factor (G-CSF); a glycoprotein that stimulates the bone marrow to produce granulocytes and stem cells	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. Peripheral Blood Stem Cells: Mobilized leukapheresis product Cyclophosphamide: An alkylating agent which causes prevention of cell division by forming adducts with DNA Mesna: Medication used to decrease the risk of hemorrhagic cystitis prophylaxis rATG: A predominantly lymphocyte-specific immunosuppressive agent which contains antibodies specific to the antigens commonly found on the surface of T cells Methylpredni
Measure Participants	17	15
Count of Participants [Participants]	2 9.1%	2 9.1%

2. Secondary Outcome

Title	Survival of Treatment
Description	Survival of Hematopoietic Stem Cell Transplant.
Time Frame	up to 12 months post treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cyclophosphamide rATG/HSCT	Cyclophosphamide rATG/Fludarabine/HSCT
Arm/Group Description	Conditioning regimen will be 200 mg/kg of intravenous cyclophosphamide given in 4 equal fractions on days -5 through -2 with IV 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. Peripheral Blood Stem Cells: Mobilized leukapheresis product Cyclophosphamide: Alkylating agent Mesna: Used to decrease the risk of hemorrhagic cystitis rATG: Immunosuppressive agent which contains antibodies specific to the antigens Methylprednisolone: Steroid Filgrastim: Granulocyte-colony stimulating factor (G-CSF); a glycoprotein that stimulates the bone marrow to produce granulocytes and stem cells	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. Peripheral Blood Stem Cells: Mobilized leukapheresis product Cyclophosphamide: An alkylating agent which causes prevention of cell division by forming adducts with DNA Mesna: Medication used to decrease the risk of hemorrhagic cystitis prophylaxis rATG: A predominantly lymphocyte-specific immunosuppressive agent which contains antibodies specific to the antigens commonly found on the surface of T cells Methylpredni
Measure Participants	22	22
Count of Participants [Participants]	22 100%	21 95.5%

Adverse Events

Time Frame	during treatment at 6 months then yearly for up to 5 years post transplant
Arm/Group Title	Cyclophosphamide rATG/HSCT		Cyclophosphamide rATG/Fludarabine/HSCT
Arm/Group Description	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. Peripheral Blood Stem Cells: Mobilized leukapheresis product Cyclophosphamide: An alkylating agent which causes prevention of cell division by forming adducts with DNA Mesna: Medication used to decrease the risk of hemorrhagic cystitis prophylaxis rATG: A predominantly lymphocyte-specific immunosuppressive agent which contains antibodies specific to the antigens commonl		Conditioning regimen will be 120 mg/kg of IV cyclophosphamide given in 2 equal fractions on days -3 and -2 with IV mesna. Rabbit antithymocyte globulin (rATG) (Thymoglobulin®) will be dosed at 0.5 mg/kg on day-5 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 IV before each dose of rATG. PBSC will be infused IV on day 0. Filgrastim 5-10 mcg/kg will be started on day + 5 and cont. until neutrophil engraftment. Peripheral Blood Stem Cells: Mobilized leukapheresis product Cyclophosphamide: Alkylating agent Mesna: Used to decrease the risk of hemorrhagic cystitis rATG: Immunosuppressive agent which contains antibodies specific to the antigens Methylprednisolone: Steroid Filgrastim: Granulocyte-colony stimulating factor (G-CSF);glycoprotein that stimulates the bone marrow to produce granulocytes/stem cells Fludarabine: Purine analog which inhibits DNA synthesis/repair
All Cause Mortality
	Cyclophosphamide rATG/HSCT		Cyclophosphamide rATG/Fludarabine/HSCT
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/22 (9.1%)		3/22 (13.6%)
Serious Adverse Events
	Cyclophosphamide rATG/HSCT		Cyclophosphamide rATG/Fludarabine/HSCT
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/22 (9.1%)		3/22 (13.6%)
General disorders
Scleroderma Disease Related	2/22 (9.1%)	2	3/22 (13.6%)	3
Other (Not Including Serious) Adverse Events
	Cyclophosphamide rATG/HSCT		Cyclophosphamide rATG/Fludarabine/HSCT
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/22 (13.6%)		2/22 (9.1%)
Cardiac disorders
Disease Related Pericardial Effusion	2/22 (9.1%)	2	2/22 (9.1%)	2
Cardiac Tamponade	0/22 (0%)	0	1/22 (4.5%)	1
Respiratory, thoracic and mediastinal disorders
Plueral Effusion	1/22 (4.5%)	1	0/22 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.