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Hematopoietic Stem Cell Therapy for Patients With Multiple Sclerosis

Primary Purpose

Multiple Sclerosis

Status
Terminated
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Hematopoietic stem cell transplantation
Sponsored by
Northwestern University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Sclerosis

Eligibility Criteria

18 Years - 50 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Age between 18-50, inclusive. Diagnosis of Multiple Sclerosis (MS) using Poser criteria (Appendix A). An Expanded Disability Status Scale (EDSS) of 2.0 - 5.5 (Appendix B). Inflammatory disease despite primary disease modifying therapy with at least 3 months of interferon. Failure is defined as two or more clinical relapses with documented neurologic changes within the year prior to the study. (NOTE: Relapses must have required treatment with corticosteroids. Sensory only relapses are excluded.) Failure may also be defined as one relapse within the year prior to study if there is evidence on MRI of active inflammation (i.e., gadolinium enhancement). Exclusion Criteria: Any illness that in the opinion of the investigators would jeopardize the ability of the patient to tolerate aggressive chemotherapy. Prior history of malignancy except localized basal cell, squamous skin cancer or carcinoma in situ of the cervix. Other malignancies for which the patient is judged to be cured, such as head and neck cancer, or breast cancer will be considered on an individual basis. Positive pregnancy test. Inability or unwillingness to pursue effective means of birth control. Effective birth control is defined as 1) refraining from all acts of vaginal intercourse (ABSTINENCE); 2) consistent use of birth control pills; 3) injectable birth control methods (Depo-provera, Norplant); 4) tubal sterilization or male partner who has undergone vasectomy; 5) placement of an intrauterine device (IUD); or 6) use, with every act of intercourse, of diaphragm with contraceptive jelly and/or condoms with contraceptive foam. Failure to willingly accept or comprehend irreversible sterility as a side effect of therapy. Forced expiratory volume in 1 second (FEV1) / forced vital capacity (FVC) < 60% of predicted after bronchodilator therapy (if necessary). Diffusing capacity of the lung for carbon monoxide (DLCO) < 50% of predicted. Resting left ventricular ejection fraction (LVEF) < 50 %. Bilirubin > 2.0 mg/dl. Serum creatinine > 2.0 mg/dl. Known hypersensitivity to mouse, rabbit, or E. Coli derived proteins, or to iron compounds/medications. Presence of metallic objects implanted in the body that would preclude the ability of the patient to safely have MRI exams. Diagnosis of primary progressive multipole sclerosis (MS). Platelet count < 100,000/ul. Psychiatric illness, mental deficiency or cognitive dysfunction making compliance with treatment or informed consent impossible. Active infection except asymptomatic bacteruria.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    Hematopoietic stem cell transplantation

    Arm Description

    All participants will undergo hematopoietic stem cell transplantation after receiving conditioning regimen.

    Outcomes

    Primary Outcome Measures

    Disease Progression
    Data are reporting number of participants with disease progression. Disease progression is defined as a 1 point increase in the Expanded Disability Status Scale (EDSS) on consecutive evaluations at least 3 months apart.

    Secondary Outcome Measures

    Survival
    Data are reporting the number of participants who survived three years after the transplant Survival of 21 participants was evaluated at three years after the transplant

    Full Information

    First Posted
    January 16, 2006
    Last Updated
    March 31, 2014
    Sponsor
    Northwestern University
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    1. Study Identification

    Unique Protocol Identification Number
    NCT00278655
    Brief Title
    Hematopoietic Stem Cell Therapy for Patients With Multiple Sclerosis
    Official Title
    Hematopoietic Stem Cell Therapy for Patients With Inflammatory Multiple Sclerosis Failing Interferon Therapy: A Phase II Multi-Center Trial
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    March 2014
    Overall Recruitment Status
    Terminated
    Study Start Date
    June 2003 (undefined)
    Primary Completion Date
    December 2011 (Actual)
    Study Completion Date
    May 2012 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    Northwestern University

    4. Oversight

    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    Multiple sclerosis is disease believed to be due to immune cells, cells which normally protect the body, but are now attacking the tissue in the brain and possibly the spinal cord. The likelihood of progression of this disease is high. This study is designed to examine whether treating patients with high dose cyclophosphamide and CAMPATH-1H (drugs which reduce the function of the immune system) followed by return of previously collected blood stem cells will stop the progression of your multiple sclerosis. Stem cells are undeveloped cells that have the capacity to grow into mature blood cells, which normally circulate in the blood stream. The purpose of the cyclophosphamide and CAMPATH-1H is to destroy the cells in your immune system which are thought to be causing your disease. The purpose of the stem cell infusion is to restore the body's blood production, which will be severely impaired by the high dose chemotherapy and to produce a normal immune system that will no longer attack the body.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Multiple Sclerosis

    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
    21 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Hematopoietic stem cell transplantation
    Arm Type
    Experimental
    Arm Description
    All participants will undergo hematopoietic stem cell transplantation after receiving conditioning regimen.
    Intervention Type
    Biological
    Intervention Name(s)
    Hematopoietic stem cell transplantation
    Intervention Description
    Autologous hematopoietic stem cell transplantation
    Primary Outcome Measure Information:
    Title
    Disease Progression
    Description
    Data are reporting number of participants with disease progression. Disease progression is defined as a 1 point increase in the Expanded Disability Status Scale (EDSS) on consecutive evaluations at least 3 months apart.
    Time Frame
    3 years after transplant
    Secondary Outcome Measure Information:
    Title
    Survival
    Description
    Data are reporting the number of participants who survived three years after the transplant Survival of 21 participants was evaluated at three years after the transplant
    Time Frame
    three years

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    50 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Age between 18-50, inclusive. Diagnosis of Multiple Sclerosis (MS) using Poser criteria (Appendix A). An Expanded Disability Status Scale (EDSS) of 2.0 - 5.5 (Appendix B). Inflammatory disease despite primary disease modifying therapy with at least 3 months of interferon. Failure is defined as two or more clinical relapses with documented neurologic changes within the year prior to the study. (NOTE: Relapses must have required treatment with corticosteroids. Sensory only relapses are excluded.) Failure may also be defined as one relapse within the year prior to study if there is evidence on MRI of active inflammation (i.e., gadolinium enhancement). Exclusion Criteria: Any illness that in the opinion of the investigators would jeopardize the ability of the patient to tolerate aggressive chemotherapy. Prior history of malignancy except localized basal cell, squamous skin cancer or carcinoma in situ of the cervix. Other malignancies for which the patient is judged to be cured, such as head and neck cancer, or breast cancer will be considered on an individual basis. Positive pregnancy test. Inability or unwillingness to pursue effective means of birth control. Effective birth control is defined as 1) refraining from all acts of vaginal intercourse (ABSTINENCE); 2) consistent use of birth control pills; 3) injectable birth control methods (Depo-provera, Norplant); 4) tubal sterilization or male partner who has undergone vasectomy; 5) placement of an intrauterine device (IUD); or 6) use, with every act of intercourse, of diaphragm with contraceptive jelly and/or condoms with contraceptive foam. Failure to willingly accept or comprehend irreversible sterility as a side effect of therapy. Forced expiratory volume in 1 second (FEV1) / forced vital capacity (FVC) < 60% of predicted after bronchodilator therapy (if necessary). Diffusing capacity of the lung for carbon monoxide (DLCO) < 50% of predicted. Resting left ventricular ejection fraction (LVEF) < 50 %. Bilirubin > 2.0 mg/dl. Serum creatinine > 2.0 mg/dl. Known hypersensitivity to mouse, rabbit, or E. Coli derived proteins, or to iron compounds/medications. Presence of metallic objects implanted in the body that would preclude the ability of the patient to safely have MRI exams. Diagnosis of primary progressive multipole sclerosis (MS). Platelet count < 100,000/ul. Psychiatric illness, mental deficiency or cognitive dysfunction making compliance with treatment or informed consent impossible. Active infection except asymptomatic bacteruria.
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Richard Burt, MD
    Organizational Affiliation
    Northwestern University
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Learn more about this trial

    Hematopoietic Stem Cell Therapy for Patients With Multiple Sclerosis

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