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Allogeneic Stem Cell Transplantation for the Treatment of Multiple Sclerosis

Primary Purpose

Multiple Sclerosis

Status
Withdrawn
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
hematopoetic stem cell infusion
Sponsored by
Talaris Therapeutics Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Sclerosis focused on measuring Relapsing-remitting multiple sclerosis, Marrow/Stem cell transplant

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    Multiple Sclerosis Patients

    Arm Description

    Recipients treated with a hematopoetic stem cell infusion from a living donor

    Outcomes

    Primary Outcome Measures

    Stem cell engraftment

    Secondary Outcome Measures

    Disease remission

    Full Information

    First Posted
    July 6, 2007
    Last Updated
    October 10, 2023
    Sponsor
    Talaris Therapeutics Inc.
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    1. Study Identification

    Unique Protocol Identification Number
    NCT00497952
    Brief Title
    Allogeneic Stem Cell Transplantation for the Treatment of Multiple Sclerosis
    Official Title
    Allogeneic Stem Cell Transplantation for the Treatment of Multiple Sclerosis
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    October 2023
    Overall Recruitment Status
    Withdrawn
    Why Stopped
    all clinical development programs terminated by sponsor
    Study Start Date
    July 2007 (undefined)
    Primary Completion Date
    December 2024 (Anticipated)
    Study Completion Date
    December 2024 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Talaris Therapeutics Inc.

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    Yes

    5. Study Description

    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Multiple Sclerosis
    Keywords
    Relapsing-remitting multiple sclerosis, Marrow/Stem cell transplant

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 1, Phase 2
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    0 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Multiple Sclerosis Patients
    Arm Type
    Experimental
    Arm Description
    Recipients treated with a hematopoetic stem cell infusion from a living donor
    Intervention Type
    Biological
    Intervention Name(s)
    hematopoetic stem cell infusion
    Intervention Description
    Enriched hematopoietic stem cell infusion
    Primary Outcome Measure Information:
    Title
    Stem cell engraftment
    Time Frame
    One month to three years
    Secondary Outcome Measure Information:
    Title
    Disease remission
    Time Frame
    3 Years

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    55 Years
    Accepts Healthy Volunteers
    No
    Eligibility 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 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
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Suzanne T Ildstad, MD
    Organizational Affiliation
    Talaris Therapeutics Inc.
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Plan to Share IPD
    Undecided

    Learn more about this trial

    Allogeneic Stem Cell Transplantation for the Treatment of Multiple Sclerosis

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