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
Study type: Interventional
Phase: Phase 2

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.
    

Detailed description: 
      MS is a chronic autoimmune disease of the central nervous system in which myelin, the
      protective coat that surrounds nerve cells, is damaged or destroyed by autoimmune T cells and
      macrophages, leading to an eventual loss of neurologic function. In a pilot study in Europe
      using high-dose chemotherapy, it was observed that 18 of 19 MS patients stabilized or
      improved clinically, and only one patient showed a new lesion on magnetic resonance imaging
      (MRI) of the brain at 4.5 years after treatment. Improvement was seen in quality-of-life
      assessments.

      In ITN033AI, high-dose chemotherapy with autologous CD34-selected hematopoietic cell
      transplantation will be given to confirm the results from the pilot study and to offer
      therapy to patients with early MS and a poor prognosis. Research studies will be performed in
      addition to clinical assessments to better understand the effect of the treatment on the
      activity of MS. High-dose chemotherapy will be used to deplete autoreactive immune cells.
      These regimens also deplete the bone marrow, the source of blood-forming CD34+ stem cells
      which causes very low blood counts. Therefore, the participant's autologous CD34+
      hematopoietic stem cells will be collected before high dose immunosuppressive therapy is
      given and then returned as a transplant post-chemotherapy. Patients will be followed closely
      after the autologous transplantation since they will be at risk for infections after
      treatment.

      At the beginning of the study, participants will undergo a number of screening and baseline
      procedures, including a physical exam, blood collection, MS-confirming neurology exams and
      questionnaires, and MRI procedures. Participants will be given prednisone and
      granulocyte-colony stimulating factor (G-CSF) to mobilize CD34+ hematopoietic stem cells from
      the bone marrow into the peripheral blood. When the peripheral blood CD34+ cell count reaches
      20,000 cells/ml or greater, these cells will be collected by leukapheresis. In this process,
      a catheter is placed into a large blood vessel, peripheral blood is withdrawn, and a high
      speed sedimentation (leukapheresis) device is used to separate and retain the cells required
      for autologous transplantation. Other blood cells are then returned to the participant's
      body. In the laboratory, the CD34+ hematopoietic stem cell graft will be selected and
      prepared from the leukapheresis collection, and stored until needed for transplant. Seven or
      more days following the collection of their autologous graft, participants will be
      hospitalized and receive high-dose chemotherapy consisting of carmustine, etoposide,
      cytarabine, and melphalan (BEAM) and thymoglobulin. This is followed by transplantation of
      the autologous hematopoietic cell graft. Participants will remain in the hospital for
      observation during recovery of their peripheral blood cell counts, as described in the
      protocol. Participants will receive G-CSF and blood transfusions, if needed, and will be
      monitored for infections. Following discharge from the hospital, eight study visits will
      occur over sixty months (five years). During these visits, participants will undergo blood
      and urine collection, MRI studies, leukapheresis, and MS neurology exams and will complete
      questionnaires.
    

Intervention name(s): Granulocyte-colony stimulating factor (G-CSF) and prednisone; Carmustine, etoposide, cytarabine, and melphalan (BEAM); Autologous hematopoietic stem cell transplant
Intervention type(s): Drug; Drug; Procedure
Intervention description(s): 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
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
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