Hematopoietic Stem Cell Transplantation in Chronic Inflammatory Demyelinating Polyneuropathy

NCT00278629 | Completed Phase 2 Results

• 1 other identifier: NU FDA CIDP.AUTO2003
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Chronic Inflammatory Demyelinating Polyneuropathy

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Survival

  Survival of participants who survived the treatment and up to 5 years post treatment.

  up to 5 years

Secondary Outcomes (3)

• Disease Improvement - Medication Free Remission

  6 months, 1, 2, 3, 4 and 5 years post transplant

• Disease Improvement - Ambulatory Assistance

  pre transplant, 6 months, 1, 2, 3, 4 and 5 years post transplant

• Change in Disability and Strength Functional Scales

  Pre Transplant, 6 months, 1, 2, 3, 4 and 5 years post transplant

Study Arms (1)

Hematopoietic Stem Cell Transplantation in CIDP

EXPERIMENTAL

Autologous hematopoietic stem cell transplantation will be performed after conditioning regimen of cyclophosphamide 200 mg/kg/intravenously(IV), rATG(thymoglobulin) 5.5 mg/kg/IV and rituximab 1000mg/IV.

Biological: hematopoietic stem cell transplantation

Interventions

hematopoietic stem cell transplantation BIOLOGICAL

Autologous hematopoietic stem cell transplantation

Hematopoietic Stem Cell Transplantation in CIDP

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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
• Persistent dysphagia documented by either aspiration or insufficient clearing on videofluoroscopic examination.
• Persistent incapacitating sensory loss (e.g. gait ataxia, falls \> 1/month)
• AND
• 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.

You may not qualify if:

• 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):
• Left ventricular ejection fraction (LVEF) \<40% or deterioration of LVEF during exercise test on multigated acquisition scan (MUGA) or echocardiogram.
• Untreated life-threatening arrhythmia.
• Active ischemic heart disease or heart failure or myocardial infarction within the last 6 months
• Diffusing capacity of lung for carbon monoxide (DLCO) \<40% or forced expiratory volume at one second (FEV1) / forced expiratory volume (FEV) \< 50%
• Serum creatinine \>2.0.
• Liver cirrhosis, transaminases \> 2 x of normal limits or bilirubin \>2.0 unless due to Gilbert disease.

Sponsors & Collaborators

• Northwestern University: lead

Study Sites (1)

Northwestern University, Feinberg School of Medicine

Chicago, Illinois, 60611, United States

Location

Related Publications (1)

• Burt RK, Balabanov R, Tavee J, Han X, Sufit R, Ajroud-Driss S, Jovanovic B, Quigley K, Arnautovic I, Helenowski I, Sharrack B. Hematopoietic stem cell transplantation for chronic inflammatory demyelinating polyradiculoneuropathy. J Neurol. 2020 Nov;267(11):3378-3391. doi: 10.1007/s00415-020-10010-6. Epub 2020 Jun 27.

  PMID: 32594300 RESULT

Related Links

• Hematopoietic Stem Cell Transplantation for Chronic Inflammatory Demyelinating Polyradiculoneuropathy

MeSH Terms

Conditions

Polyradiculoneuropathy, Chronic Inflammatory Demyelinating

Interventions

Hematopoietic Stem Cell Transplantation

Condition Hierarchy (Ancestors)

Polyradiculoneuropathy; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Polyneuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Autoimmune Diseases; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative

Results Point of Contact

• Title: Kathleen Quigley
• Organization: Northwestern University

k-quigley@northwestern.edu

312-695-8192

Study Officials

• Richard Burt, MD

  Northwestern University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: January 16, 2006
• First Posted: January 18, 2006
• Study Start: February 21, 2005
• Primary Completion: January 14, 2017
• Study Completion: November 4, 2019
• Last Updated: July 23, 2020
• Results First Posted: July 23, 2020

Record last verified: 2020-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)