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High-dose Cyclophosphamide for Moderate to Severe Refractory Chronic Inflammatory Demyelinating Polyneuropathy

Phase 2
Withdrawn
Conditions
Chronic Inflammatory Demyelinating Polyneuropathy
Registration Number
NCT01236456
Lead Sponsor
Stony Brook University
Brief Summary

The primary endpoint of this study is to determine what percentage of patients receiving high-dose Cyclophosphamide may experience a halt in the worsening of their disease or experience improvement of their disease and for how long the benefit may last.

Detailed Description

Chronic inflammatory demyelinating polyneuropathy (CIDP) is a common and under-recognized peripheral neuropathy that is thought to be immune-mediated. Randomized, placebo controlled clinical trials in CIDP demonstrate benefit from treatment with corticosteroids, plasmapheresis, and IV Ig. However, not all patients respond to these therapies. IV cyclophosphamide, cyclosporine, interferons, total lymphoid irradiation, and mycophenolate mofetil have been proposed as appropriate therapies for refractory patients.

Patients with CIDP often respond to immune-modulating treatment. However, the high rate of relapse and treatment-related side effects result in poor long-term outcomes for many patients. CIDP is assumed to be an autoimmune disease, but the pathogenesis is poorly understood. T cell infiltrates are predominantly CD8, suggesting a T cell mediated process. There is not, however, restricted T cell receptor Vbeta utilization seen in sural nerve biopsies. Immunoglobulin and complement deposits noted on the myelin sheaths support an antibody-mediated process. Antibodies to the P0 myelin protein are seen in a minority of patients. High-dose cyclophosphamide is believed to eradicate both B and T lymphocytes. This therapy does not damage hematopoietic stem cells, which allows for rapid white cell recovery without stem cell rescue.

Recruitment & Eligibility

Status
WITHDRAWN
Sex
All
Target Recruitment
Not specified
Inclusion Criteria
  • Diagnosis of CIDP according to the American Academy of Neurology clinical and electrophysiologic criteria
  • Age >18 but < 75 years
  • Modified Rankin Scale score of >3 after two standard treatment regimens
  • Patient must have a left ventricular ejection fraction of >45%
  • Serum Creatinine <3mg/dL
  • Willingness to participate in a clinical trial
Exclusion Criteria
  • Patients who are preterminal or moribund
  • Patients with active malignancies
  • Patients with chromosomal abnormalities or peripheral blood counts suggestive of myelodysplastic syndrome
  • Patients with active bacterial or fungal infections requiring oral or intravenous antimicrobials are not eligible until resolution of the infection
  • Pregnant women and breast-feeding women

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Primary Outcome Measures
NameTimeMethod
The primary endpoint of this study is to evaluate the response rate of CIDP patients as determined by functional score, change in Summated compound motor action potential and strength, after high-dose cyclophosphamide therapy.
Secondary Outcome Measures
NameTimeMethod
The secondary endpoint of this study is to determine remission duration.
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