High-Dose Immunosuppression and Autologous Transplantation for Multiple Sclerosis (HALT MS) Study
Condition: Relapsing-Remitting Multiple Sclerosis
MeSH terms: Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Sclerosis
Intervention: Granulocyte-colony stimulating factor (G-CSF) and prednisone; Carmustine, etoposide, cytarabine, and melphalan (BEAM); Autologous hematopoietic stem cell transplant
Intervention description: Growth factor regimen; occurs at study entry; High-dose chemotherapy; occurs seven or more days following collection of autologous graft; Occurs after growth factor regimen and collection of autologous graft
Intervention MeSH terms: Cytarabine; Prednisone; Etoposide; Melphalan; Carmustine; Lenograstim
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 25.0
Sex: All
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: No
Keywords: hematopoietic stem cell transplantation; HCT- autologous hematopoietic cell transplant; HDIT-high-dose immunosuppressive therapy; BEAM -Carmustine (BCNU), Etoposide (VP-16), Cytarabine (ara-C), and Melphalan

Summary:

      The purpose of this study is to determine the effectiveness of a new treatment for multiple
      sclerosis (MS), a serious disease in which the immune system attacks the brain and spinal
      cord. MS can be progressive and severe and lead to significant disability. The study
      treatment involves the use of high-dose chemotherapeutic drugs to suppress the immune system.
      The participant's own (autologous) blood-forming (hematopoietic, CD34+) stem cells are
      collected before the chemotherapy is given, and then transplanted back into the body
      following treatment. Transplantation of autologous hematopoietic stem cells is required to
      prevent very prolonged periods of low blood cell counts after the high-dose chemotherapy.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis of relapsing-remitting or progressive-relapsing multiple sclerosis for less
             than 15 years using McDonald Criteria. More information on this criterion can be found
             in the protocol

          -  Score between 3.0 and 5.5 on the Expanded Disability Status Scale (EDSS)

          -  T2 abnormalities on brain MRI consistent with MS

          -  Two or more relapses in 18 months time on interferon (IFN), glatiramer acetate (GA),
             natalizumab or cytotoxic therapy with EDSS increase of 1.0 or greater for participants
             with EDSS at screening of 3.0 to 3.5 (0.5 or greater for participants with EDSS at
             screening of 4.0 to 5.5) sustained at least 4 weeks after at least one of these
             relapses OR one relapse on IFN, GA, natalizumab or cytotoxic therapy with EDSS
             increase of 1.5 or greater (1.0 for subjects with EDSS at screening of 5.5) sustained
             at least 4 weeks, together with MRI changes consistent with poor prognosis. More
             information on this criterion can be found in the protocol.

          -  On IFN or GA for at least 6 months before the relapses occur that are counted to
             satisfy previous inclusion criterion OR have received adequate doses of natalizumab or
             cytotoxic therapy on a treatment schedule before the relapses occur that are counted
             to satisfy previous inclusion criterion

          -  Approval by an MS Review Panel to participate in the study. More information on this
             criterion can be found in the protocol

          -  In good clinical condition with adequate organ function and without coexisting medical
             problems that would increase the risk to the participant

          -  Willing to use acceptable methods of contraception

          -  Willing and able to comply with all study requirements and

          -  Willing to accept and comprehend irreversible sterility as side effect of therapy.

        Exclusion Criteria:

          -  Primary progressive MS

          -  Secondary progressive MS without relapses (i.e., progression without exacerbations or
             relapses) for 12 or more months

          -  Neuromyelitis optica, a disease similar to MS

          -  Initiation of new immunosuppressant treatment after the participant becomes eligible
             for the protocol or continuance of immunosuppressant drugs after the participant is
             screened for the protocol. Treatment with IFN, GA, or corticosteroids is permitted
             after the participant becomes eligible for the protocol.

          -  Lapse of greater than 6 months between the time a participant is eligible for the
             protocol and initiation of protocol treatment except when judged acceptable by the MS
             Review Panel

          -  Prior treatment with investigational immunosuppressive agents within 3 months of study
             eligibility

          -  Positive baseline plasma and CSF testing for JC virus or a brain MRI that has changes
             consistent with a diagnosis of progressive multifocal encephalopathy (PML)

          -  History of cytopenia consistent with the diagnosis of myelodysplastic syndrome (MDS)

          -  Active hepatitis B or C infection, cirrhosis, or HIV infection

          -  Uncontrolled diabetes mellitus

          -  Uncontrolled viral, fungal, or bacterial infection. Patients with asymptomatic
             bacteriuria are not excluded

          -  Any illness that would jeopardize the ability to tolerate aggressive chemotherapy

          -  Prior history of malignancy, except localized basal cell or squamous skin cancer.
             Other malignancies for which the subject is judged cured by the administered therapy
             will be considered on an individual basis.

          -  Hypersensitivity to mouse, rabbit, or Escherichia coli-derived proteins or to iron
             compounds/medications

          -  Metallic objects implanted in the body that would affect MRI exams

          -  Psychiatric illness, mental deficiency, or cognitive dysfunction or

          -  Pregnancy.