Donor Stem Cell Transplantation for the Treatment of Multiple Sclerosis - Full Text View

Sponsor:	University of Louisville
Information provided by:	University of Louisville
ClinicalTrials.gov Identifier:	NCT00497952

Purpose

While the cause of MS in not known, there is an autoimmune component that destroys nerve cells. Autoimmunity is a condition where an individual's immune system attacks his/her own cells. Bone marrow stem cell transplantation has been shown to halt autoimmunity. Stem cell transplant can be performed using the patient's own cells, or donor cells. The general consensus in the field is that donor transplant is most likely to halt disease progression. This study is designed to evaluate the safety of a donor transplant procedure as a therapy for relapsing remitting multiple sclerosis (RRMS).

Two factors limit the widespread application of traditional donor stem cell transplant: 1) preparing the patient for transplant (conditioning); and 2) graft-versus-host disease (GVHD). Traditional conditioning destroys the recipient's immune system and requires that the marrow transplant be successful because the patient is unable to fight off infection if the donor cells do not survive. GVHD occurs when donor immune cells recognize the recipient's cells as foreign tissue and attack them. Severe GVHD can result in death. This study utilizes a new approach to conditioning which leaves the patient's immune system intact. The transplant product is depleted of GVHD-producing cells but retains tolerance-promoting cells, called facilitating cells, which are intended to ensure the donor and recipient cells coexists peacefully. The toxicity of conditioning and transplantation is significantly reduced. The end result is a marrow system that contains recipient and donor cells, a state called mixed chimerism.

In this study, we will determine the appropriate cell dose to safely establish mixed chimerism following partial conditioning in patients with RRMS. The study takes a gradual approach to increasing the cell dose to achieve mixed chimerism. Each patient will receive a cell dose one unit above the dose received by the most recent safely transplanted patient. We believe this study will provide a breakthrough in the treatment of MS. The goal of this proposal is to evaluate the potential of safely establishing mixed chimerism to interrupt the autoimmune process and end the devastating effects of MS.

Condition	Intervention	Phase
Multiple Sclerosis	Procedure: Stem cell transplant	Phase I Phase II

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
Official Title:	Allogeneic Stem Cell Transplantation for the Treatment of Multiple Sclerosis

Resource links provided by NLM:

MedlinePlus related topics: Multiple Sclerosis

U.S. FDA Resources

Further study details as provided by University of Louisville:

Primary Outcome Measures:

Stem cell engraftment/chimerism [ Time Frame: Months: 3, 6, 9, 12, 18, 24 & 36 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Disease remission [ Time Frame: 3 Years ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	15
Study Start Date:	July 2007
Estimated Primary Completion Date:	July 2016 (Final data collection date for primary outcome measure)

Intervention Details:

Bone marrow will be processed via a new technology which will enrich hematopoietic stem cells and graft facilitating cells. Monitoring for chimerism will be done at key time points.

Eligibility

Ages Eligible for Study:	18 Years to 55 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Clinically definite MS according to the McDonald criteria
Confirmed diagnosis of relapsing-remitting MS.
Age between 18 and 55 years
Extended Disability Status Score (EDSS) between 0 and 5.0
Independently ambulatory (eligible for inclusion if subject was acutely non-ambulatory within the previous year and return of function is substantiated with EDSS score.
Relapse within the last year or sustained disability progression of 1.0 for six months
Treatment with high dose, high frequency Interferon-β therapy, or failure to tolerate Interferon-β therapy
DLCO> 50% (unless cleared by physician)
EF > 40% (unless cleared by cardiologist)
Required initial laboratory data (obtained within 30 days prior to transplant, unless otherwise specified)
- HIV-1,2 antigen and antibody negative
- HBsAg negative (chronic hepatitis B carriers without clinical evidence of liver disease can be considered on an individual basis if it is determined that the added risk is justified by the prognosis and lack of treatment alternatives)
- Hepatitis C antibody negative (positive antibody allowed if antigen (RNA)-negative and no clinical evidence of cirrhosis)
- CMV, hepatitis B, HTLV-1,2, EBV, and Herpes antibody status known
- Pregnancy test negative (women of childbearing potential only)
No life-threatening organ dysfunction.
- Uncontrolled or severe cardiovascular disease, including recent (<6 months) myocardial infarction, angina (symptomatic despite optimal medical management), life-threatening arrhythmia or hypertension
Able to give informed consent

Exclusion Criteria:

Women who are of child bearing potential must have a negative pregnancy test (serum pregnancy test [HCG]) within 48 hours of initiating total body irradiation and agree to use reliable contraception for 1 year following transplant.
Concomitant severe diseases (respiratory, renal, liver, cardiac failures, psychiatric disorders, neoplasms)
Recurrent urinary, pulmonary infections.
Active bacterial, viral, or fungal infection
Active peptic ulcer disease
Previous treatments with total lymphoid irradiation or total body irradiation
Interferon-neutralizing antibody positive with a titer greater than 20
Relapse in the month preceding enrollment
Poor compliance

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00497952

Locations

United States, Kentucky
Institute for Cellular Therapeutics, University of Louisville
Louisville, Kentucky, United States, 40202

Sponsors and Collaborators

University of Louisville

Investigators

Study Director:	Suzanne T. Ildstad, M.D.	Institute for Cellular Therapeutics, University of Louisville
Principal Investigator:	Roger Herzig, M.D.	James Graham Brown Cancer Center, University of Louisville
Principal Investigator:	Stephen Kirzinger, MD	University of Louisville

More Information

No publications provided

Responsible Party:	Institute for Cellular Therapeutics ( Suzanne T. Ildstad, M.D. )
Study ID Numbers:	20052664, 335-06 (UofL ID)
Study First Received:	July 6, 2007
Last Updated:	March 18, 2009
ClinicalTrials.gov Identifier:	NCT00497952 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by University of Louisville:

Relapsing-remitting multiple sclerosis
Stem cell transplant
Mixed chimerism

Additional relevant MeSH terms:

Pathologic Processes
Autoimmune Diseases
Multiple Sclerosis
Immune System Diseases
Demyelinating Diseases

Nervous System Diseases
Demyelinating Autoimmune Diseases, CNS
Sclerosis
Autoimmune Diseases of the Nervous System

ClinicalTrials.gov processed this record on November 20, 2009