Hematopoietic Stem Cell Transplantation in Chronic Inflammatory Demyelinating Polyneuropathy
Condition: Chronic Inflammatory Demyelinating Polyneuropathy
MeSH terms: Polyneuropathies; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating
Intervention: hematopoietic stem cell transplantation
Intervention description: Autologous hematopoietic stem cell transplantation
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 80.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No

Summary:

      Chronic inflammatory demyelinating polyneuropathy is disease believed to be due to immune
      cells, cells which normally protect the body, but are now attacking the nerves in the body.
      As a result, the affected nerves fail to respond, or respond only weakly, to stimuli causing
      numbing, tingling, pain, and progressive muscle weakness.The likelihood of progression of the
      disease is high. This study is designed to examine whether treating patients with high dose
      cyclophosphamide (a drug which reduces the function of the immune system) and ATG (a protein
      that kills the immune cells that are thought to be causing disease), followed by return of
      the previously collected blood stem cells will stop the progression of CIDP. 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 high dose cyclophosphamide and ATG is to
      destroy the cells in the immune system. The purpose of the stem cell infusion is to evaluate
      whether this treatment will produce a normal immune system that will no longer attack the
      body.
    

Eligibility criteria:

        Inclusion criteria:

          -  Definite CIDP according to the European Federation of Neurological
             Societies/Peripheral Nerve Society (EFNS/PNS) criteria

        AND

          -  Clinically typical or atypical CIDP

        AND

          -  Failure to tolerate or respond to, or an incomplete response to, or relapse after at
             least 3 months of conventional treatment consisting of corticosteroids (equivalent
             dosage of prednisone 1.0/mg/day to 0.75mg/kg/day to start with adequate tapering
             trials of no less than 0.5mg/kg/day), and/or either intravenous immunoglobulin (IVIg)
             or plasmapheresis or cytoxan or rituxan

          -  Failure to respond to therapy is defined by:

               1. Persistent muscle weakness Grade 3/5 or worse (MRC) in at least one muscle or
                  grade 4/5 in at least two muscle groups OR

               2. Persistent dysphagia documented by either aspiration or insufficient clearing on
                  videofluoroscopic examination.

                  OR

               3. Persistent incapacitating sensory loss (e.g. gait ataxia, falls > 1/month)

                  AND

               4. If patients are on IVIG or plasmapheresis, neurologic condition is documented to
                  deteriorate (for example, new or increase finger tip paresthesias or increased
                  leg heaviness) upon stopping IVIG (or plasmapheresis)@

          -  Monoclonal gammopathy of undetermined significance (MUGS) (in which the pathogenesis
             of are thought to be the same as CIDP) will be allowed provided bone marrow aspirate
             and biopsy rules out multiple myeloma.

          -  Other immune mediated or suspected immune mediated neuropathies such as multifocal
             motor neuropathy or anti-myelin-associated glycoprotein (anti-MAG) neuropathy may be
             treated but will be analyzed and reported separately.

        Exclusion Criteria:

          -  Any evidence of hereditary cause for neuropathy that is known or likely hereditary
             demyelination neuropathy because of family history, foot deformity, mutilation of
             hands or feet, retinitis pigmentosa, ichthyosis, or liability to pressure palsies.

          -  Diphtheria, drug, or toxin exposure likely to be cause of neuropathy

          -  Conditions in which the pathogenesis of the neuropathy may be different from CIDP such
             as: Lyme disease (Borrelia burgdorferi infection), POEMS syndrome, Osteosclerotic
             myeloma, malignancies such as Waldenstrom macroglobulinemia, and Castleman's)

          -  Multiple myeloma

          -  HIV positive

          -  Insulin dependent Diabetes mellitus

          -  Chronic active hepatitis

          -  Age > 65 years old or < 18 years old

          -  Significant end organ damage such as (not caused by CIDP):

               1. Left ventricular ejection fraction (LVEF) <40% or deterioration of LVEF during
                  exercise test on multigated acquisition scan (MUGA) or echocardiogram.

               2. Untreated life-threatening arrhythmia.

               3. Active ischemic heart disease or heart failure or myocardial infarction within
                  the last 6 months

               4. Diffusing capacity of lung for carbon monoxide (DLCO) <40% or forced expiratory
                  volume at one second (FEV1) / forced expiratory volume (FEV) < 50%

               5. Serum creatinine >2.0.

               6. Liver cirrhosis, transaminases > 2 x of normal limits or bilirubin >2.0 unless
                  due to Gilbert disease.

          -  Prior history of malignancy except localized basal cell or squamous skin cancer or
             other localized cancer considered cured only by surgery

          -  Positive pregnancy test, inability or unwillingness to pursue effective means of birth
             control, or failure to willingly accept or comprehend irreversible sterility as a side
             effect of therapy.

          -  Psychiatric illness or mental deficiency making compliance with treatment or informed
             consent impossible.

          -  Inability to give informed consent.

          -  Major hematological abnormalities such as platelet count less than 100,000/ul or
             absolute neutrophil count (ANC) less than 1000/ul.

          -  Failure to collect at least 2.0 x 106 cluster of differentiation 34 (CD34+) cells by
             apheresis and, if necessary, bone marrow harvest is a contraindication to treatment,
             i.e., receiving the conditioning regimen.