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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
Sponsor:
Information provided by (Responsible Party):
Richard Burt, MD, Northwestern University

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Scleroderma, Systemic
Interventions Biological: Peripheral Blood Stem Cells
Drug: Cyclophosphamide
Drug: Mesna
Drug: rATG
Drug: Methylprednisolone
Drug: Filgrastim
Drug: Fludarabine
Enrollment 44
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Cyclophosphamide rATG/HSCT Cyclophosphamide rATG/Fludarabine/HSCT
Hide 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
Arm/Group Title Cyclophosphamide rATG/HSCT Cyclophosphamide rATG/Fludarabine/HSCT Total
Hide 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 Number of Baseline Participants 22 22 44
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 22 participants 22 participants 44 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
22
 100.0%
22
 100.0%
44
 100.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous  
Mean (Full Range)
Unit of measure:  Years
Number Analyzed 22 participants 22 participants 44 participants
42.8
(23 to 59)
45.6
(19 to 60)
44.2
(19 to 60)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 22 participants 22 participants 44 participants
Female
16
  72.7%
18
  81.8%
34
  77.3%
Male
6
  27.3%
4
  18.2%
10
  22.7%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 22 participants 22 participants 44 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   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%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 22 participants 22 participants 44 participants
22 22 44
Skin Score Prior to Treatment   [1] 
Mean (Full Range)
Unit of measure:  Units on a scale
Number Analyzed 22 participants 22 participants 44 participants
26.1
(13 to 48)
22.8
(11 to 40)
24.14
(11 to 48)
[1]
Measure Description: Modified Rodnan Skin Score range from 0 (normal thickness of skin) to 51 (severe thickness of skin)
1.Primary Outcome
Title Number of Participants With Treatment Failure
Hide Description

Treatment failure will not occur until a minimum of 12 months after treatment at which time failure is defined as:

  1. 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
  2. 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Cyclophosphamide rATG/HSCT Cyclophosphamide rATG/Fludarabine/HSCT
Hide 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

Overall Number of Participants Analyzed 17 15
Measure Type: Count of Participants
Unit of Measure: Participants
2
  11.8%
2
  13.3%
2.Secondary Outcome
Title Survival of Treatment
Hide Description Survival of Hematopoietic Stem Cell Transplant.
Time Frame up to 12 months post treatment
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Cyclophosphamide rATG/HSCT Cyclophosphamide rATG/Fludarabine/HSCT
Hide 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

Overall Number of Participants Analyzed 22 22
Measure Type: Count of Participants
Unit of Measure: Participants
22
 100.0%
21
  95.5%
Time Frame during treatment at 6 months then yearly for up to 5 years post transplant
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Cyclophosphamide rATG/HSCT Cyclophosphamide rATG/Fludarabine/HSCT
Hide 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 (%) Affected / at Risk (%)
Total   2/22 (9.09%)      3/22 (13.64%)    
Hide Serious Adverse Events
Cyclophosphamide rATG/HSCT Cyclophosphamide rATG/Fludarabine/HSCT
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/22 (9.09%)      3/22 (13.64%)    
General disorders     
Scleroderma Disease Related  [1]  2/22 (9.09%)  2 3/22 (13.64%)  3
Indicates events were collected by systematic assessment
[1]
Mortality due to disease progression
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Cyclophosphamide rATG/HSCT Cyclophosphamide rATG/Fludarabine/HSCT
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/22 (13.64%)      2/22 (9.09%)    
Cardiac disorders     
Disease Related Pericardial Effusion  [1]  2/22 (9.09%)  2 2/22 (9.09%)  2
Cardiac Tamponade  [2]  0/22 (0.00%)  0 1/22 (4.55%)  1
Respiratory, thoracic and mediastinal disorders     
Plueral Effusion  [3]  1/22 (4.55%)  1 0/22 (0.00%)  0
Indicates events were collected by systematic assessment
[1]
Scleroderma related pericardial effusion
[2]
Cardiac Tamponade Requiring Pericardiocentesis
[3]
Pleural Effusion
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Kathleen Quigley
Organization: Northwestern University
Phone: 312-695-8192
EMail: k-quigley@northwestern.edu
Layout table for additonal information
Responsible Party: Richard Burt, MD, Northwestern University
ClinicalTrials.gov Identifier: NCT01445821    
Other Study ID Numbers: ASSIST IIb
First Submitted: September 29, 2011
First Posted: October 4, 2011
Results First Submitted: June 15, 2020
Results First Posted: July 23, 2020
Last Update Posted: July 23, 2020