Clinical trial NCT03342638
Conditions: Multiple Sclerosis, Relapsing-Remitting
Keywords: Autologous Stem Cell Transplantation Stem Cells Hematopoietic Stem Cell Transplantation
Sponsor: Northwestern University
Start date: 2017-11-08; Completion date: 2019-10-09
Enrollment: 66 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Randomized study of autologous un-manipulated peripheral blood hematopoietic stem cell transplant (HSCT) comparing two regimens: (1) cyclophosphamide and rabbit anti-thymoglobulin (rATG) versus (2) cyclophosphamide, rATG, and Intravenous Immunoglobulin (IVIg).

Detailed description:
Multiple sclerosis (MS) is at onset an immune-mediated demyelinating disease. In most cases, it starts as a relapsing-remitting disease with distinct attacks and no symptoms between flares. Over years or decades, virtually all cases transition into a progressive disease in which insidious and slow neurologic deterioration occurs with or without acute flares. Relapsing-remitting disease is often responsive to immune suppressive or modulating therapies, while immune based therapies are generally ineffective in patients with a progressive clinical course. This clinical course and response to immune suppression, as well as neuropathology and neuroimaging studies, suggest that disease progression is associated with axonal atrophy. Disability correlates better with measures of axonal atrophy than immune mediated demyelination. Therefore, immune based therapies, in order to be effective, need to be started early in the disease course while MS is predominantly an immune-mediated and inflammatory disease. While current immune based therapies delay disability, no intervention has been proven to prevent progressive disability.The investigators propose a randomized study of autologous unmanipulated peripheral blood hematopoietic stem cell transplant (HSCT) comparing two different conditioning regimens: (1) cyclophosphamide and rabbit anti-thymoglobulin (rATG) versus (2) cyclophosphamide, rATG, and Intravenous Immunoglobulin (IVIg).

Arms: arm 1: Hematopoietic Stem Cell Therapy will be performed as follows: Autologous stem cells will be infused after conditioning with cyclophosphamide, mesna, rATG (rabbit), and methylprednisolone. Granulocyte-colony stimulating factor (G-CSF) will be administered post-transplant. arm 2: Hematopoietic Stem Cell Therapy will be performed as follows: Autologous stem cells will be infused after conditioning with cyclophosphamide, mesna, rATG (rabbit), and methylprednisolone. IVIg and G-CSF will be administered post-transplant.
Interventions: intervention 1: Cyclophosphamide intervention 2: Mesna intervention 3: rATG intervention 4: Methylprednisolone intervention 5: G-CSF intervention 6: IVIg intervention 7: Autologous Stem Cells
Intervention descriptions: intervention 1: Potent immunosuppressive agent; an alkylating agent intervention 2: Medication used to decrease the risk of hemorrhagic cystitis prophylaxis intervention 3: A predominantly lymphocyte-specific immunosuppressive agent which contains antibodies specific to the antigens commonly found on the surface of T cells intervention 4: Steroid intervention 5: Granulocyte-colony stimulating factor; a glycoprotein that stimulates the bone marrow to produce granulocytes and stem cells and release them into the bloodstream intervention 6: Sterile, purified immunoglobulin G (IgG) products manufactured from pooled human plasma and typically contain more than 95% unmodified IgG, which has intact Fc-dependent effector functions and only trace amounts of immunoglobulin A (IgA) or immunoglobulin M (IgM). intervention 7: Infusion of participant's own stem cells

Protocol documents:
Prot_002.pdf: