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High-Dose Immunosuppression and Autologous Transplantation for Multiple Sclerosis (HALT MS) Study

This study has been completed.
Sponsor:
Collaborator:
Immune Tolerance Network (ITN)
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00288626
First received: February 7, 2006
Last updated: February 17, 2017
Last verified: February 2017
Results First Received: December 6, 2016  
Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment;   Masking: No masking;   Primary Purpose: Treatment
Condition: Relapsing-Remitting Multiple Sclerosis
Interventions: Drug: Granulocyte-colony stimulating factor (G-CSF) and prednisone
Drug: Carmustine, etoposide, cytarabine, and melphalan (BEAM)
Procedure: Autologous hematopoietic stem cell transplant

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
36 participants were screened and 25 of those participants were enrolled at 3 sites in the US between August 2006 and August 2009. 24 participants were transplanted with the cellular product between February 2007 and April 2010

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
HDIT and HCT Participants recv'd Granulocyte Colony Stimulating Factor (G-CSF) by injection for 4-5 days to increase the number of blood stem cells in the blood stream by mobilizing them from the bone marrow. Leukapheresis was performed until ≥ 2.0 x 10^6 CD34+ hematopoietic progenitor cells (HPCs) per kg were collected and frozen for future use. After ≥7 days following the last G-CSF dose, patients were hospitalized and received high-dose immunosuppression (HDIT) and immunosuppressive agent thymoglobulin 2.5 mg/kg over the course of 6 days. HDIT consisted of carmustine 300mg/m^2, etoposide 200 mg/m^2 cytarabine 200 mg/m^2, and melphalan 140 mg/m^2. CD34+ HPCs were thawed and infused according to institutional best practice for blood component transfusion over approximately 30 minutes. Patients were hospitalized until recovery of ANC to > 500/uL for at least 2 days. Prednisone was administered (0.5 mg/kg/day) from Days 7 to 21 after HCT and tapered over 2 weeks to prevent engraftment syndrome.

Participant Flow:   Overall Study
    HDIT and HCT
STARTED   24 
COMPLETED   17 
NOT COMPLETED   7 
Death                3 
Withdrawal by Subject                4 



  Baseline Characteristics
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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.
Participants who received High-Dose Immunosuppressive Therapy (HDIT)and Autologous CD34+ Hematopoietic Stem Cell Transplant (HCT)

Reporting Groups
  Description
HDIT and HCT Participants recv'd Granulocyte Colony Stimulating Factor (G-CSF) by injection for 4-5 days to increase the number of blood stem cells in the blood stream by mobilizing them from the bone marrow. Leukapheresis was performed until ≥2.0 x 10^6 CD34+ hematopoietic progenitor cells (HPCs) per kg were collected and frozen for future use. After ≥7 days following the last G-CSF dose, patients were hospitalized and received high-dose immunosuppression (HDIT) and immunosuppressive agent thymoglobulin 2.5 mg/kg over the course of 6 days. HDIT consisted of carmustine 300mg/m^2, etoposide 200 mg/m^2 cytarabine 200 mg/m^2, and melphalan 140 mg/m^2. CD34+ HPCs were thawed and infused according to institutional best practice for blood component transfusion over approximately 30 minutes. Patients were hospitalized until recovery of ANC to > 500/uL for at least 2 days. Prednisone was administered (0.5 mg/kg/day) from Days 7 to 21 after HCT and tapered over 2 weeks to prevent engraftment syndrome.

Baseline Measures
   HDIT and HCT 
Overall Participants Analyzed 
[Units: Participants]
 24 
Age 
[Units: Years]
Mean (Standard Deviation)
 36.5  (7.7) 
Sex: Female, Male 
[Units: Participants]
Count of Participants
 
Female      16  66.7% 
Male      8  33.3% 
Ethnicity (NIH/OMB) 
[Units: Participants]
Count of Participants
 
Hispanic or Latino      0   0.0% 
Not Hispanic or Latino      23  95.8% 
Unknown or Not Reported      1   4.2% 
Race (NIH/OMB) 
[Units: Participants]
Count of Participants
 
American Indian or Alaska Native      0   0.0% 
Asian      0   0.0% 
Native Hawaiian or Other Pacific Islander      0   0.0% 
Black or African American      0   0.0% 
White      23  95.8% 
More than one race      1   4.2% 
Unknown or Not Reported      0   0.0% 
Region of Enrollment 
[Units: Participants]
 
United States   24 
Expanded Disability Status Scale (EDSS) at Baseline [1] 
[Units: Units on a scale]
Mean (Standard Deviation)
 4.4  (.64) 
[1] Kurtzke’s Expanded Disability Status Scale (EDSS) assesses disability in Multiple Sclerosis patients. Eight functional systems are evaluated: visual, brain stem, pyramidal, cerebellar, sensory, bowel and bladder, cerebral, and ambulation. The overall score ranges from 0 (normal neurological exam) to 10 (death due to MS).
Number of Gadolinium-Enhanced Lesions at Baseline [1] 
[Units: Lesions per scan]
Mean (Standard Deviation)
 2.3  (5.8) 
[1] Multiple sclerosis disease-related lesions were assessed by gadolinium-enhanced magnetic resonance imaging (MRI). More lesions indicate more severe disease.
T1 Lesion Volume at Baseline [1] 
[Units: Milliliters]
Mean (Standard Deviation)
 1.2  (2.7) 
[1] A T1-weighted magnetic resonance imaging (MRI) scan assessed the volume of T1 lesions.
T2 Lesion Volume at Baseline [1] 
[Units: Milliliters]
Mean (Standard Deviation)
 11.1  (13.7) 
[1] A T2-weighted magnetic resonance imaging (MRI) scan assessed the volume of T2 lesions in the brain.
Normalized Brain Volume at Screening [1] 
[Units: Liters]
Mean (Standard Deviation)
 1.6  (0.1) 
[1] Magnetic resonance imaging (MRI) scan techniques measured ventricular volumes and grey and white matter brain volumes


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Event-Free Survival Probability During the 5 Years After Transplant   [ Time Frame: 5 years ]

2.  Secondary:   Event-Free Survival Probability During the 3 Years After Transplant   [ Time Frame: 3 years ]

3.  Secondary:   Survival From Treatment-Related Mortality   [ Time Frame: From study entry to death, loss to follow-up, or the end of the study, whichever came first, up to 6 years ]

4.  Secondary:   Overall Survival   [ Time Frame: From study entry to death, loss to follow-up, or the end of the study, whichever came first, up to 6 years ]

5.  Secondary:   Survival From MS-Related Mortality   [ Time Frame: From study entry to death, loss to follow-up, or the end of the study, whichever came first, up to 6 years ]

6.  Secondary:   Percent of Participants Who Experienced All-Cause Morbidity   [ Time Frame: From the time of enrollment until completion of the 5-year follow-up, an average of 6 years. ]

7.  Secondary:   Percent of Participants Who Experienced All-Cause Morbidity Within 12 Months of Post-HCT   [ Time Frame: From the time of Autologous CD34+ Hematopoietic Stem Cell Transplant (HCT) to 1 year after HCT. ]

8.  Secondary:   Time to Neutrophil Engraftment   [ Time Frame: From time of graft infusion to time of engraftment, up to 6 years ]

9.  Secondary:   Time to Platelet Engraftment   [ Time Frame: From time of graft infusion to time of engraftment, up to 6 years ]

10.  Secondary:   Event-Free Survival Probability After Transplant   [ Time Frame: 1, 2, and 4 years after HCT ]

11.  Secondary:   MS Progression-Free Survival Probability After Transplant   [ Time Frame: 1 to 5 years after HCT ]

12.  Secondary:   MRI Activity-Free Survival Probability After Transplant   [ Time Frame: 1 to 5 years after HCT ]

13.  Secondary:   MS Relapse-Free Survival Probability After Transplant   [ Time Frame: 1 to 5 years after HCT ]

14.  Secondary:   Disease-Modifying Therapy Survival Probability After Transplant   [ Time Frame: 1 to 5 years after HCT ]

15.  Secondary:   Change From Baseline in Extended Disability Status Scale (EDSS)   [ Time Frame: 6 months to 5 years after HCT ]

16.  Secondary:   Change From Baseline in Number of Gadolinium-Enhanced Lesions   [ Time Frame: 8 weeks to 5 years after HCT ]

17.  Secondary:   Number of New T2-Weighted Lesions From Baseline   [ Time Frame: 6 Months to 5 years after HCT ]

18.  Secondary:   Change From Baseline in T2-Weighted Lesion Volume   [ Time Frame: 8 weeks to 5 years after HCT ]

19.  Secondary:   Change From Baseline in T1-Weighted Lesion Volume   [ Time Frame: 8 weeks to 5 years after HCT ]

20.  Secondary:   Percent Change From Screening in Brain Volume   [ Time Frame: 8 weeks to 5 years after HCT ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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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
24 of the 25 planned transplants occurred. One of the enrolled participants developed adverse events that caused withdrawal from the study before the planned transplant.


  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 of Results:
Other Publications:

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00288626     History of Changes
Other Study ID Numbers: DAIT ITN033AI
DAIT SCMS2
Study First Received: February 7, 2006
Results First Received: December 6, 2016
Last Updated: February 17, 2017