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Allogeneic Stem Cell Transplantation for the Treatment of Multiple Sclerosis

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ClinicalTrials.gov Identifier: NCT00497952
Recruitment Status : Active, not recruiting
First Posted : July 9, 2007
Last Update Posted : October 8, 2020
Sponsor:
Information provided by (Responsible Party):
Talaris Therapeutics Inc.

Tracking Information
First Submitted Date  ICMJE July 6, 2007
First Posted Date  ICMJE July 9, 2007
Last Update Posted Date October 8, 2020
Study Start Date  ICMJE July 2007
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 9, 2012)
Stem cell engraftment [ Time Frame: One month to three years ]
Original Primary Outcome Measures  ICMJE
 (submitted: July 6, 2007)
Stem cell engraftment/chimerism
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 23, 2008)
Disease remission [ Time Frame: 3 Years ]
Original Secondary Outcome Measures  ICMJE
 (submitted: July 6, 2007)
Disease remission
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Allogeneic Stem Cell Transplantation for the Treatment of Multiple Sclerosis
Official Title  ICMJE Allogeneic Stem Cell Transplantation for the Treatment of Multiple Sclerosis
Brief Summary The goal of this research study is to establish chimerism with the goal to halt disease progression in patients with Multiple Sclerosis.
Detailed Description

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 study is to evaluate the potential of safely establishing mixed chimerism to interrupt the autoimmune process and end the devastating effects of MS.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Multiple Sclerosis
Intervention  ICMJE Biological: hematopoetic stem cell infusion
Enriched hematopoietic stem cell infusion
Study Arms  ICMJE Experimental: Multiple Sclerosis Patients
Recipients treated with a hematopoetic stem cell infusion from a living donor
Intervention: Biological: hematopoetic stem cell infusion
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: November 18, 2010)
3
Original Estimated Enrollment  ICMJE
 (submitted: July 6, 2007)
15
Estimated Study Completion Date  ICMJE December 2020
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
  • Diffusing capacity of the lung for carbon monoxide (DLCO)> 50% (unless cleared by physician)
  • Ejection fraction (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)
    • Cytomegalovirus (CMV), hepatitis B, Human T-lymphotropic virus (HTLV)-1,2, Epstein-Barr virus (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 - human chorionic gonadotrophin (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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 55 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries United States
 
Administrative Information
NCT Number  ICMJE NCT00497952
Other Study ID Numbers  ICMJE ICT-13080-122206
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Talaris Therapeutics Inc.
Study Sponsor  ICMJE Talaris Therapeutics Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Suzanne T Ildstad, MD Talaris Therapeutics Inc.
PRS Account Talaris Therapeutics Inc.
Verification Date October 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP