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Scleroderma: Cyclophosphamide or Transplantation (SCOT)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00114530
First received: June 15, 2005
Last updated: June 16, 2017
Last verified: June 2017
Results First Received: May 5, 2017  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: No masking;   Primary Purpose: Treatment
Conditions: Scleroderma, Systemic
Sclerosis
Autoimmune Disease
Interventions: Biological: mHSCT
Drug: cyclophosphamide

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
mHSCT Participants were administered granulocyte colony stimulating factor (G-CSF) and had hematopoietic stem cells removed from their blood. They then underwent high-dose immunosuppressive therapy using a conditioning regimen of total body irradiation (800 cGy given over 2 days with lung and kidney shielding limiting exposure to 200cGy), cyclophosphamide (60 mg/kg/day for 2 days), IV Methylprednisolone (1 mg/kg/day for 3 days), and equine antithymocyte globulin (ATGAM) (15 mg/kg/day for 3 days). Purified autologous stem cell were infused at a dose of >2.5x106 CD34+ cells/kg. After transplantation, participants received additional doses of IV Methylprednisolone (1 mg/kg/day for 3 days) and ATGAM (15 mg/kg/day for 3 days.)
Cyclophosphamide Participants received 12 monthly pulses of high-dose intravenous cyclophosphamide (an initial dose of 500 mg/m^2, followed by 11 doses of 750 mg/m^2).

Participant Flow:   Overall Study
    mHSCT   Cyclophosphamide
STARTED   36   39 
COMPLETED   27 [1]   19 [1] 
NOT COMPLETED   9   20 
Death                3                11 
Lost to Follow-up                1                1 
Physician Decision                1                1 
Withdrawal by Subject                2                6 
Breast Cancer                1                0 
Subject decision after endpoint failure                0                1 
Ineligible                1                0 
[1] Completed 72 mo, 54 mo after failure, or at least 54 mo at study end (last patient’s 54 mo visit)



  Baseline Characteristics
  Hide Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Randomized intent to treat

Reporting Groups
  Description
mHSCT Participants were administered granulocyte colony stimulating factor (G-CSF) and had hematopoietic stem cells removed from their blood. They then underwent high-dose immunosuppressive therapy using a conditioning regimen of total body irradiation (800 cGy given over 2 days with lung and kidney shielding limiting exposure to 200cGy), cyclophosphamide (60 mg/kg/day for 2 days), IV Methylprednisolone (1 mg/kg/day for 3 days), and equine antithymocyte globulin (ATGAM) (15 mg/kg/day for 3 days). Purified autologous stem cell were infused at a dose of >2.5x106 CD34+ cells/kg. After transplantation, participants received additional doses of IV Methylprednisolone (1 mg/kg/day for 3 days) and ATGAM (15 mg/kg/day for 3 days.)
Cyclophosphamide Participants received 12 monthly pulses of high-dose intravenous cyclophosphamide (an initial dose of 500 mg/m^2, followed by 11 doses of 750 mg/m^2).
Total Total of all reporting groups

Baseline Measures
   mHSCT   Cyclophosphamide   Total 
Overall Participants Analyzed 
[Units: Participants]
 36   39   75 
Age 
[Units: Participants]
Count of Participants
     
<=18 years      0   0.0%      0   0.0%      0   0.0% 
Between 18 and 65 years      35  97.2%      38  97.4%      73  97.3% 
>=65 years      1   2.8%      1   2.6%      2   2.7% 
Age 
[Units: Years]
Mean (Standard Deviation)
 44.9  (10.90)   46.9  (10.43)   45.9  (10.63) 
Sex: Female, Male 
[Units: Participants]
Count of Participants
     
Female      19  52.8%      29  74.4%      48  64.0% 
Male      17  47.2%      10  25.6%      27  36.0% 
Ethnicity (NIH/OMB) 
[Units: Participants]
Count of Participants
     
Hispanic or Latino      3   8.3%      5  12.8%      8  10.7% 
Not Hispanic or Latino      32  88.9%      34  87.2%      66  88.0% 
Unknown or Not Reported      1   2.8%      0   0.0%      1   1.3% 
Race (NIH/OMB) 
[Units: Participants]
Count of Participants
     
American Indian or Alaska Native      0   0.0%      0   0.0%      0   0.0% 
Asian      2   5.6%      1   2.6%      3   4.0% 
Native Hawaiian or Other Pacific Islander      0   0.0%      0   0.0%      0   0.0% 
Black or African American      2   5.6%      4  10.3%      6   8.0% 
White      29  80.6%      31  79.5%      60  80.0% 
More than one race      2   5.6%      3   7.7%      5   6.7% 
Unknown or Not Reported      1   2.8%      0   0.0%      1   1.3% 
Region of Enrollment 
[Units: Participants]
     
Canada   1   2   3 
United States   35   37   72 
Health Assessment Questionnaire - Disability Index (HAQ-DI) [1] 
[Units: Units on a scale]
Mean (Standard Deviation)
 1.2  (0.65)   1.4  (0.86)   1.3  (0.77) 
[1] HAQ-DI is a self-reported questionnaire of functionality that includes questions in 8 domains (dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities). The final score ranges from 0 to 3, where a higher HAQ-DI score indicates a worse outcome.
Short Form 36 Health Survey (SF-36) [1] 
[Units: Units on a scale]
Mean (Standard Deviation)
     
Physical Component Score   29.5  (9.20)   28.9  (9.46)   29.2  (9.27) 
Mental Component Score   44.7  (10.70)   44.6  (9.86)   44.6  (10.21) 
[1] The SF-36 measures health-related quality of life. It has 36 items and 2 component scores, the Physical Component Score and the Mental Component Score. Each component was transformed into a 0-100 scale (higher numbers indicate greater quality of life) and normalized to have a mean of 50 and standard deviation of 10 for the 1998 general US population.
Diffusion in Liters of Carbon Monoxide (DLCO) (Percent-Predicted) [1] 
[Units: Percent predicted]
Mean (Standard Deviation)
 53.9  (7.63)   52.7  (8.19)   53.3  (7.90) 
[1] Diffusion in liters of carbon monoxide (DLCO) is a measure of lung function. Predicted values for DLCO were computed using the Crapo Morris equations and adjusted per the Cotes formula for anemia, if a participant’s hemoglobin was <13 or >17 gm/dL, and altitude (Calgary site only).
Forced Vital Capacity (FVC) (Percent-Predicted) [1] 
[Units: Percent predicted]
Mean (Standard Deviation)
 74.5  (14.77)   73.8  (16.98)   74.2  (15.86) 
[1] Forced Vital Capacity (FVC) is the amount of air that can be forcibly exhaled after a full breath and is a measure of lung function. Predicted FVC was based on institutional standards.
Modified Rodnan Skin Score (mRSS) [1] 
[Units: Units on a scale]
Mean (Standard Deviation)
 28.5  (8.72)   30.8  (10.55)   29.7  (9.72) 
[1] The Modified Rodnan Skin Score (mRSS) is a measure of skin thickness. Skin thickness in 17 anatomic areas was rated on a 0-3 scale and scores are summed to obtain the mRSS (range from 0 - 51), with higher mRSS scores indicating worse disease activity.
Disease-Modifying Anti-Rheumatic Drug (DMARD) Use Within 6 Months of Randomization [1] 
[Units: Participants]
Count of Participants
 26   25   51 
[1] Use of any disease-modifying antirheumatic drugs (DMARDs) within six months prior to randomization. DMARDS can include, but are not limited to, methotrexate, cyclophosphamide, azathioprine, leflunomide, mycophenolate mofetil, D-penicillamine, tacrolimus, cyclosporine, prednisone >10 mg, and TNF-blockers.
Disease-Modifying Anti-Rheumatic Drug (DMARD) Use [1] 
[Units: Participants]
Count of Participants
 27   32   59 
[1] Any use of disease-modifying antirheumatic drugs (DMARDs) prior to randomization. DMARDS can include, but are not limited to, methotrexate, cyclophosphamide, azathioprine, leflunomide, mycophenolate mofetil, D-penicillamine, tacrolimus, cyclosporine, prednisone >10 mg, and TNF-blockers.


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Global Rank Composite Score (GRCS) (Month 54, ITT)   [ Time Frame: 54 Months Post-Randomization ]

2.  Secondary:   Global Rank Composite Score (GRCS) (Month 54, PP)   [ Time Frame: 54 Months Post-Randomization ]

3.  Secondary:   Global Rank Composite Score (GRCS) (Month 48, ITT)   [ Time Frame: 48 Months Post-Randomization ]

4.  Secondary:   Global Rank Composite Score (GRCS) (Month 48, PP)   [ Time Frame: 48 Months Post-Randomization ]

5.  Secondary:   Event-Free Survival (EFS) (Month 54, ITT)   [ Time Frame: 54 Months Post-Randomization ]

6.  Secondary:   Event-Free Survival (EFS) (Month 54, PP)   [ Time Frame: 54 Months Post-Randomization ]

7.  Secondary:   Event-Free Survival (EFS) (Month 48, ITT)   [ Time Frame: 48 Months Post-Randomization ]

8.  Secondary:   Event-Free Survival (EFS) (Month 48, PP)   [ Time Frame: 48 Months Post-Randomization ]

9.  Secondary:   Treatment-Related Mortality (Month 54, ITT)   [ Time Frame: 54 Months Post-Randomization ]

10.  Secondary:   Treatment-Related Mortality (Month 54, PP)   [ Time Frame: 54 Months Post-Randomization ]

11.  Secondary:   Treatment-Related Mortality (Month 48, ITT)   [ Time Frame: 48 Months Post-Randomization ]

12.  Secondary:   Treatment-Related Mortality (Month 48, PP)   [ Time Frame: 48 Months Post-Randomization ]

13.  Secondary:   All-Cause Mortality (Month 54, ITT)   [ Time Frame: 54 Months Post-Randomization ]

14.  Secondary:   All-Cause Mortality (Month 54, PP)   [ Time Frame: 54 Months Post-Randomization ]

15.  Secondary:   All-Cause Mortality (Month 48, ITT)   [ Time Frame: 48 Months Post-Randomization ]

16.  Secondary:   All-Cause Mortality (Month 48, PP)   [ Time Frame: 48 Months Post-Randomization ]

17.  Secondary:   Change From Baseline to Month 54 in Health Assessment Questionnaire - Disability Index (HAQ-DI) (ITT)   [ Time Frame: 54 Months Post-Randomization ]

18.  Secondary:   Change From Baseline to Month 54 in Health Assessment Questionnaire - Disability Index (HAQ-DI) (PP)   [ Time Frame: 54 Months Post-Randomization ]

19.  Secondary:   Change From Baseline to Month 54 in Short Form 36 Health Survey (SF-36) (ITT)   [ Time Frame: 54 Months Post-Randomization ]

20.  Secondary:   Change From Baseline to Month 54 in Short Form 36 Health Survey (SF-36) (PP)   [ Time Frame: 54 Months Post-Randomization ]

21.  Secondary:   Change From Baseline to Month 54 in Diffusion in Liters of Carbon Monoxide (DLCO) (ITT)   [ Time Frame: 54 Months Post-Randomization ]

22.  Secondary:   Change From Baseline to Month 54 in Diffusion in Liters of Carbon Monoxide (DLCO) (PP)   [ Time Frame: 54 Months Post-Randomization ]

23.  Secondary:   Change From Baseline to Month 54 in Forced Vital Capacity (FVC) (ITT)   [ Time Frame: 54 Months Post-Randomization ]

24.  Secondary:   Change From Baseline to Month 54 in Forced Vital Capacity (FVC) (PP)   [ Time Frame: 54 Months Post-Randomization ]

25.  Secondary:   Change From Baseline to Month 54 in Modified Rodnan Skin Score (mRSS) (ITT)   [ Time Frame: 54 Months Post-Randomization ]

26.  Secondary:   Change From Baseline to Month 54 in Modified Rodnan Skin Score (mRSS) (PP)   [ Time Frame: 54 Months Post-Randomization ]

27.  Secondary:   New or Worsening Arrhythmias, Congestive Heart Failure, or Pericardial Effusion (ITT)   [ Time Frame: 54 Months Post-Randomization ]

28.  Secondary:   New or Worsening Arrhythmias, Congestive Heart Failure, or Pericardial Effusion (PP)   [ Time Frame: 54 Months Post-Randomization ]

29.  Secondary:   New or Worsening Pulmonary Hypertension (ITT)   [ Time Frame: 54 Months Post-Randomization ]

30.  Secondary:   New or Worsening Pulmonary Hypertension (PP)   [ Time Frame: 54 Months Post-Randomization ]

31.  Secondary:   Occurrence of Scleroderma Renal Crisis (ITT)   [ Time Frame: 54 Months Post-Randomization ]

32.  Secondary:   Occurrence of Scleroderma Renal Crisis (PP)   [ Time Frame: 54 Months Post-Randomization ]

33.  Secondary:   Documented Myositis (ITT)   [ Time Frame: 54 Months Post-Randomization ]

34.  Secondary:   Documented Myositis (PP)   [ Time Frame: 54 Months Post-Randomization ]

35.  Secondary:   Initiating Use of Disease-Modifying Antirheumatic Drugs (DMARDs) by Month 54 (ITT)   [ Time Frame: 54 Months Post-Randomization ]

36.  Secondary:   Initiating Use of Disease-Modifying Antirheumatic Drugs by Month 54 (DMARDs) (PP)   [ Time Frame: 54 Months Post-Randomization ]

37.  Secondary:   Regimen-Related Toxicities   [ Time Frame: Randomization through end of study follow-up (up to Month 72 post-randomization) ]

38.  Secondary:   Number of Subjects With Regimen-Related Toxicities   [ Time Frame: Randomization through end of study follow-up (up to Month 72 post-randomization). ]

39.  Secondary:   Infectious Complications   [ Time Frame: Randomization through end of study follow-up (up to Month 72 post-randomization). ]

40.  Secondary:   Number of Subjects With Infectious Complications   [ Time Frame: Randomization through end of study follow-up (up to Month 72 post-randomization). ]

41.  Secondary:   Time to Absolute Neutrophil Count Engraftment   [ Time Frame: 28 days post-transplant ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
Results are applicable for SSc with severe internal organ disease and may not be generalizable to all those with dcSSc. The hierarchical components of the GRCS are specific to this SSc population and may not be generalizable to other SSc populations.


  More Information
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Certain Agreements:  
Principal Investigators are NOT 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.


Results Point of Contact:  
Name/Title: Director, Clinical Research Operations Program
Organization: DAIT/NIAID
phone: 301-594-7669
e-mail: DAITClinicalTrialsGov@niaid.nih.gov


Publications:


Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00114530     History of Changes
Obsolete Identifiers: NCT00472277, NCT00545038, NCT00848614, NCT00871221, NCT00872508
Other Study ID Numbers: DAIT SCSSc-01
SCOT ( Other Identifier: Sponsor and Investigators )
Study First Received: June 15, 2005
Results First Received: May 5, 2017
Last Updated: June 16, 2017